Trial Outcomes & Findings for Radiation Therapy Plus Temozolomide and Pembrolizumab With and Without HSPPC-96 in Newly Diagnosed Glioblastoma (GBM) (NCT NCT03018288)

Last Updated: 2025-08-08

Results Overview

One-year overall survival (OS) rate is defined as the percentage of participants who from time of registration survived to one year in newly diagnosed O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) unmethylated Glioblastoma (GBM) participants treated with radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab followed by Pembrolizumab + TMZ +/- heat-shock protein peptide complex-96 (HSPPC-96) x 6 cycles (1 cycle is 9 weeks) months. Rate of OS is measured by Kaplan-Meier method.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

90 participants

Primary outcome timeframe

One year

Results posted on

2025-08-08

Participant Flow

Participant milestones

Participant milestones
Measure	Vaccine Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Heat Shock Protein Peptide Complex-96.(HSPPC-96). Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of HSPPC-96 0.4mL intradermal vaccine. HSPPC-96 vaccine will then be given 21 days after the day 5 dose of temozolomide. HSPPC-96 vaccine will be given for 6 cycles or until supply runs out. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Placebo Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Placebo Vaccine. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of placebo vaccine. Placebo vaccine will then be given 21 days after the day 5 dose of temozolomide. Placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Ancillary Treatment Radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as 30-minute IV infusion every 3 weeks on days 1, 22, and 43. After completion of 6 cycles, participants may continue on Pembrolizumab for an additional 12 months if felt to be of benefit by the treating physician. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Enrolled But Not Treated Participants were enrolled but not treated.
Overall Study STARTED	8	9	15	58
Overall Study Surgery	8	9	15	56
Overall Study Sufficient Vaccine Made (Minimum of Four). Participants Randomized to Arm 3 and Arm 4	8	9	0	0
Overall Study No Sufficient Vaccine Made (Minimum of Four). Participants Randomized to Arm 2.	0	0	15	0
Overall Study COMPLETED	7	8	12	0
Overall Study NOT COMPLETED	1	1	3	58

Reasons for withdrawal

Reasons for withdrawal
Measure	Vaccine Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Heat Shock Protein Peptide Complex-96.(HSPPC-96). Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of HSPPC-96 0.4mL intradermal vaccine. HSPPC-96 vaccine will then be given 21 days after the day 5 dose of temozolomide. HSPPC-96 vaccine will be given for 6 cycles or until supply runs out. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Placebo Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Placebo Vaccine. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of placebo vaccine. Placebo vaccine will then be given 21 days after the day 5 dose of temozolomide. Placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Ancillary Treatment Radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as 30-minute IV infusion every 3 weeks on days 1, 22, and 43. After completion of 6 cycles, participants may continue on Pembrolizumab for an additional 12 months if felt to be of benefit by the treating physician. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Enrolled But Not Treated Participants were enrolled but not treated.
Overall Study Participants withdrew consent before surgery.	0	0	0	1
Overall Study Participant withdrew consent.	0	0	1	0
Overall Study Switched to alternative treatment.	0	0	1	0
Overall Study Participant withdrew consent for personal reasons.	0	0	1	0
Overall Study Screen failures	0	0	0	51
Overall Study Chose treatment outside of UNC	0	0	0	1
Overall Study Unable to comply with protocol requirements	1	1	0	1
Overall Study Participant declined to participate (before treatment started)	0	0	0	3
Overall Study Physician Decision	0	0	0	1

Baseline Characteristics

Radiation Therapy Plus Temozolomide and Pembrolizumab With and Without HSPPC-96 in Newly Diagnosed Glioblastoma (GBM)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vaccine n=8 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Heat Shock Protein Peptide Complex-96.(HSPPC-96). Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of HSPPC-96 0.4mL intradermal vaccine. HSPPC-96 vaccine will then be given 21 days after the day 5 dose of temozolomide. HSPPC-96 vaccine will be given for 6 cycles or until supply runs out. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Placebo n=9 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Placebo Vaccine. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of placebo vaccine. Placebo vaccine will then be given 21 days after the day 5 dose of temozolomide. Placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Ancillary Treatment n=15 Participants Radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as 30-minute IV infusion every 3 weeks on days 1, 22, and 43. After completion of 6 cycles, participants may continue on Pembrolizumab for an additional 12 months if felt to be of benefit by the treating physician. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Enrolled But Not Treated n=58 Participants Participants were enrolled but not treated.	Total n=90 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants	36 Participants n=4 Participants	56 Participants n=21 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	22 Participants n=4 Participants	34 Participants n=21 Participants
Age, Continuous	64 years STANDARD_DEVIATION 11.88 • n=5 Participants	58.34 years STANDARD_DEVIATION 12.6 • n=7 Participants	58.65 years STANDARD_DEVIATION 8.76 • n=5 Participants	59.05 years STANDARD_DEVIATION 14.71 • n=4 Participants	59.9 years STANDARD_DEVIATION 10.64 • n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants	29 Participants n=4 Participants	38 Participants n=21 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants	29 Participants n=4 Participants	52 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants	57 Participants n=4 Participants	86 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	6 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants	10 Participants n=21 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants	45 Participants n=4 Participants	72 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants
Region of Enrollment United States	8 participants n=5 Participants	9 participants n=7 Participants	15 participants n=5 Participants	58 participants n=4 Participants	90 participants n=21 Participants

PRIMARY outcome

Timeframe: One year

Outcome measures

Outcome measures
Measure	Vaccine n=8 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Heat Shock Protein Peptide Complex-96.(HSPPC-96). Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of HSPPC-96 0.4mL intradermal vaccine. HSPPC-96 vaccine will then be given 21 days after the day 5 dose of temozolomide. HSPPC-96 vaccine will be given for 6 cycles or until supply runs out. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Placebo n=9 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Placebo Vaccine. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of placebo vaccine. Placebo vaccine will then be given 21 days after the day 5 dose of temozolomide. Placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Ancillary Treatment n=15 Participants Radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as 30-minute IV infusion every 3 weeks on days 1, 22, and 43. After completion of 6 cycles, participants may continue on Pembrolizumab for an additional 12 months if felt to be of benefit by the treating physician. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Probably Related Adverse events probably related to Pembrolizumab.	Definitely Related Adverse events definitely related to Pembrolizumab.
One-year Overall Survival (OS) Rate	52.5 percentage of participants Interval 24.5 to 100.0	71.4 percentage of participants Interval 44.7 to 100.0	42.3 percentage of participants Interval 20.4 to 87.9	—	—

SECONDARY outcome

Timeframe: After treatment, up to 26 months

Population: 4 out of 8 participants in vaccine group were evaluable for response. 6 out of the 9 participants in the placebo group were evaluable for response. 7 out of the 15 ancillary participants were evaluable for response.

Response was determined by the Response Assessment in Neuro-Oncology Criteria (RANO) criteria and reported with 95% confidence intervals using exact binomial probability distributions. Complete response is no T1 gadolinium enhancing disease or stable or decreasing T2/fluid-attenuated inversion recovery (FLAIR). Partial response is ≥ 50% decrease in T1 gadolinium enhancing disease or stable or decreasing T2/FLAIR. Stable disease is \<50% decrease but \<25% increase in T1 gadolinium enhancing disease or stable or decreasing T2/FLAIR. Progressive disease is ≥25% incT1 gadolinium enhancing disease, appearance of new lesions or increase in T2/FLAIR.

Outcome measures

Outcome measures
Measure	Vaccine n=4 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Heat Shock Protein Peptide Complex-96.(HSPPC-96). Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of HSPPC-96 0.4mL intradermal vaccine. HSPPC-96 vaccine will then be given 21 days after the day 5 dose of temozolomide. HSPPC-96 vaccine will be given for 6 cycles or until supply runs out. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Placebo n=6 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Placebo Vaccine. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of placebo vaccine. Placebo vaccine will then be given 21 days after the day 5 dose of temozolomide. Placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Ancillary Treatment n=7 Participants Radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as 30-minute IV infusion every 3 weeks on days 1, 22, and 43. After completion of 6 cycles, participants may continue on Pembrolizumab for an additional 12 months if felt to be of benefit by the treating physician. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Probably Related Adverse events probably related to Pembrolizumab.	Definitely Related Adverse events definitely related to Pembrolizumab.
Response Rate Complete Response	0 percentage of participants Interval 0.0 to 60.2	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 41.0	—	—
Response Rate Partial Response	0 percentage of participants Interval 0.0 to 60.2	0 percentage of participants Interval 0.0 to 45.9	14.3 percentage of participants Interval 0.4 to 57.9	—	—
Response Rate Stable Disease	100.0 percentage of participants Interval 39.8 to	100.0 percentage of participants Interval 54.1 to 100.0	28.6 percentage of participants Interval 3.7 to 71.0	—	—
Response Rate Progressive Disease	0 percentage of participants Interval 0.0 to 60.2	0 percentage of participants Interval 0.0 to 45.9	57.1 percentage of participants Interval 18.4 to 90.1	—	—

SECONDARY outcome

Timeframe: Time from registration to the time of death or off study up to 26 months

OS is defined as the time from registration to the time of death. Kaplan-Meier curves will be used to analyze overall survival.

Outcome measures

Outcome measures
Measure	Vaccine n=8 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Heat Shock Protein Peptide Complex-96.(HSPPC-96). Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of HSPPC-96 0.4mL intradermal vaccine. HSPPC-96 vaccine will then be given 21 days after the day 5 dose of temozolomide. HSPPC-96 vaccine will be given for 6 cycles or until supply runs out. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Placebo n=9 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Placebo Vaccine. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of placebo vaccine. Placebo vaccine will then be given 21 days after the day 5 dose of temozolomide. Placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Ancillary Treatment n=15 Participants Radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as 30-minute IV infusion every 3 weeks on days 1, 22, and 43. After completion of 6 cycles, participants may continue on Pembrolizumab for an additional 12 months if felt to be of benefit by the treating physician. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Probably Related Adverse events probably related to Pembrolizumab.	Definitely Related Adverse events definitely related to Pembrolizumab.
Overall Survival (OS)	14.4 Months Interval 9.9 to The follow-up is not long enough to estimate the upper bound of the confidence intervals for median OS.	14.1 Months Interval 11.5 to The follow-up is not long enough to estimate the upper bound of the confidence intervals for median OS.	10.1 Months Interval 8.2 to The follow-up is not long enough to estimate the upper bound of the confidence intervals for median OS.	—	—

SECONDARY outcome

Timeframe: 6, 12 and 24 months, post-registration

Participants who are alive at 6, 12 and 24 months, post-registration determined from the level of the Kaplan-Meier curves at these time points.

Outcome measures

Outcome measures
Measure	Vaccine n=8 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Heat Shock Protein Peptide Complex-96.(HSPPC-96). Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of HSPPC-96 0.4mL intradermal vaccine. HSPPC-96 vaccine will then be given 21 days after the day 5 dose of temozolomide. HSPPC-96 vaccine will be given for 6 cycles or until supply runs out. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Placebo n=9 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Placebo Vaccine. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of placebo vaccine. Placebo vaccine will then be given 21 days after the day 5 dose of temozolomide. Placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Ancillary Treatment n=15 Participants Radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as 30-minute IV infusion every 3 weeks on days 1, 22, and 43. After completion of 6 cycles, participants may continue on Pembrolizumab for an additional 12 months if felt to be of benefit by the treating physician. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Probably Related Adverse events probably related to Pembrolizumab.	Definitely Related Adverse events definitely related to Pembrolizumab.
Overall Survival at 6, 12 and 24 Months, Post-registration 6 months post registration	87.5 Percentage of participants Interval 67.3 to 100.0	100.0 Percentage of participants Interval 100.0 to 100.0	84.6 Percentage of participants Interval 67.1 to 100.0	—	—
Overall Survival at 6, 12 and 24 Months, Post-registration 12 months post registration	52.5 Percentage of participants Interval 24.5 to 100.0	71.4 Percentage of participants Interval 44.7 to 100.0	42.3 Percentage of participants Interval 20.4 to 87.9	—	—
Overall Survival at 6, 12 and 24 Months, Post-registration 24 months post registration	17.5 Percentage of participants Interval 3.0 to 100.0	14.3 Percentage of participants Interval 2.3 to 87.7	10.6 Percentage of participants Interval 1.7 to 67.1	—	—

SECONDARY outcome

Timeframe: Start of treatment until participant is off study, approximately 61.5 months

Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. And Grade 5 is death related to adverse event.

Outcome measures

Outcome measures
Measure	Vaccine n=8 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Heat Shock Protein Peptide Complex-96.(HSPPC-96). Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of HSPPC-96 0.4mL intradermal vaccine. HSPPC-96 vaccine will then be given 21 days after the day 5 dose of temozolomide. HSPPC-96 vaccine will be given for 6 cycles or until supply runs out. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Placebo n=8 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Placebo Vaccine. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of placebo vaccine. Placebo vaccine will then be given 21 days after the day 5 dose of temozolomide. Placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Ancillary Treatment n=8 Participants Radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as 30-minute IV infusion every 3 weeks on days 1, 22, and 43. After completion of 6 cycles, participants may continue on Pembrolizumab for an additional 12 months if felt to be of benefit by the treating physician. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Probably Related n=8 Participants Adverse events probably related to Pembrolizumab.	Definitely Related n=8 Participants Adverse events definitely related to Pembrolizumab.
Vaccine Cohort: Number of Adverse Events Grades 2-5, Unrelated, Unlikely, Possibly, Probably, and/or Definitely Related to Pembrolizumab Grade 2	14 adverse events	28 adverse events	10 adverse events	0 adverse events	0 adverse events
Vaccine Cohort: Number of Adverse Events Grades 2-5, Unrelated, Unlikely, Possibly, Probably, and/or Definitely Related to Pembrolizumab Grade 3	8 adverse events	13 adverse events	3 adverse events	0 adverse events	0 adverse events
Vaccine Cohort: Number of Adverse Events Grades 2-5, Unrelated, Unlikely, Possibly, Probably, and/or Definitely Related to Pembrolizumab Grade 4	1 adverse events	1 adverse events	0 adverse events	0 adverse events	0 adverse events
Vaccine Cohort: Number of Adverse Events Grades 2-5, Unrelated, Unlikely, Possibly, Probably, and/or Definitely Related to Pembrolizumab Grade 5	1 adverse events	0 adverse events	0 adverse events	0 adverse events	0 adverse events

SECONDARY outcome

Timeframe: Start of treatment until participant is off study, approximately 61.5 months

Outcome measures

Outcome measures
Measure	Vaccine n=9 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Heat Shock Protein Peptide Complex-96.(HSPPC-96). Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of HSPPC-96 0.4mL intradermal vaccine. HSPPC-96 vaccine will then be given 21 days after the day 5 dose of temozolomide. HSPPC-96 vaccine will be given for 6 cycles or until supply runs out. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Placebo n=9 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Placebo Vaccine. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of placebo vaccine. Placebo vaccine will then be given 21 days after the day 5 dose of temozolomide. Placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Ancillary Treatment n=9 Participants Radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as 30-minute IV infusion every 3 weeks on days 1, 22, and 43. After completion of 6 cycles, participants may continue on Pembrolizumab for an additional 12 months if felt to be of benefit by the treating physician. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Probably Related n=9 Participants Adverse events probably related to Pembrolizumab.	Definitely Related n=9 Participants Adverse events definitely related to Pembrolizumab.
Placebo Cohort: Number of Adverse Events Grades 2-5, Unrelated, Unlikely, Possibly, Probably, and/or Definitely Related to Pembrolizumab Grade 2	5 Adverse events	19 Adverse events	11 Adverse events	4 Adverse events	2 Adverse events
Placebo Cohort: Number of Adverse Events Grades 2-5, Unrelated, Unlikely, Possibly, Probably, and/or Definitely Related to Pembrolizumab Grade 3	8 Adverse events	5 Adverse events	1 Adverse events	7 Adverse events	1 Adverse events
Placebo Cohort: Number of Adverse Events Grades 2-5, Unrelated, Unlikely, Possibly, Probably, and/or Definitely Related to Pembrolizumab Grade 4	0 Adverse events	0 Adverse events	0 Adverse events	1 Adverse events	1 Adverse events
Placebo Cohort: Number of Adverse Events Grades 2-5, Unrelated, Unlikely, Possibly, Probably, and/or Definitely Related to Pembrolizumab Grade 5	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events

SECONDARY outcome

Timeframe: Start of treatment until participant is off study, approximately 61.5 months

Outcome measures

Outcome measures
Measure	Vaccine n=15 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Heat Shock Protein Peptide Complex-96.(HSPPC-96). Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of HSPPC-96 0.4mL intradermal vaccine. HSPPC-96 vaccine will then be given 21 days after the day 5 dose of temozolomide. HSPPC-96 vaccine will be given for 6 cycles or until supply runs out. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Placebo n=15 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Placebo Vaccine. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of placebo vaccine. Placebo vaccine will then be given 21 days after the day 5 dose of temozolomide. Placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Ancillary Treatment n=15 Participants Radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as 30-minute IV infusion every 3 weeks on days 1, 22, and 43. After completion of 6 cycles, participants may continue on Pembrolizumab for an additional 12 months if felt to be of benefit by the treating physician. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Probably Related n=15 Participants Adverse events probably related to Pembrolizumab.	Definitely Related n=15 Participants Adverse events definitely related to Pembrolizumab.
Ancillary Treatment Cohort: Number of Adverse Events Grades 2-5, Unrelated, Unlikely, Possibly, Probably, and/or Definitely Related to Pembrolizumab Grade 2	17 Adverse Events	43 Adverse Events	13 Adverse Events	0 Adverse Events	2 Adverse Events
Ancillary Treatment Cohort: Number of Adverse Events Grades 2-5, Unrelated, Unlikely, Possibly, Probably, and/or Definitely Related to Pembrolizumab Grade 3	18 Adverse Events	25 Adverse Events	7 Adverse Events	3 Adverse Events	2 Adverse Events
Ancillary Treatment Cohort: Number of Adverse Events Grades 2-5, Unrelated, Unlikely, Possibly, Probably, and/or Definitely Related to Pembrolizumab Grade 4	1 Adverse Events	5 Adverse Events	2 Adverse Events	0 Adverse Events	1 Adverse Events
Ancillary Treatment Cohort: Number of Adverse Events Grades 2-5, Unrelated, Unlikely, Possibly, Probably, and/or Definitely Related to Pembrolizumab Grade 5	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events	0 Adverse Events

SECONDARY outcome

Timeframe: Baseline, end of treatment or discontinuation, and 30 days after last dose

Population: There are different numbers for overall participants analyzed because we don't have that data available (i.e., a few participants didn't do a baseline questionnaire).

To evaluate the occurrence of symptoms and correlate to disease progression and tolerance to treatment using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). Participants rate their symptoms on a questionnaire using an 11-point scale (0-10). 0 is "not present" and 10 is "as bad as you can imagine." Differences of at least 2 points will be classified as the minimum clinically meaningful change in the symptom severity measures. Higher score indicates worse severity.

Outcome measures

Outcome measures
Measure	Vaccine n=8 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Heat Shock Protein Peptide Complex-96.(HSPPC-96). Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of HSPPC-96 0.4mL intradermal vaccine. HSPPC-96 vaccine will then be given 21 days after the day 5 dose of temozolomide. HSPPC-96 vaccine will be given for 6 cycles or until supply runs out. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Placebo n=8 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Placebo Vaccine. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of placebo vaccine. Placebo vaccine will then be given 21 days after the day 5 dose of temozolomide. Placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Ancillary Treatment n=13 Participants Radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as 30-minute IV infusion every 3 weeks on days 1, 22, and 43. After completion of 6 cycles, participants may continue on Pembrolizumab for an additional 12 months if felt to be of benefit by the treating physician. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Probably Related Adverse events probably related to Pembrolizumab.	Definitely Related Adverse events definitely related to Pembrolizumab.
Mean Symptom Severity Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). Baseline	1.4 Score on a scale Standard Deviation 0.8	1.3 Score on a scale Standard Deviation 0.9	1.2 Score on a scale Standard Deviation 1.1	—	—
Mean Symptom Severity Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). End of treatment or discontinuation	4.0 Score on a scale Standard Deviation 1.5	1.4 Score on a scale Standard Deviation 0.8	2.4 Score on a scale Standard Deviation 1.8	—	—
Mean Symptom Severity Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). 30 days after last dose	—	1.7 Score on a scale	1.9 Score on a scale Standard Deviation 0.5	—	—

SECONDARY outcome

Timeframe: Baseline, end of treatment or discontinuation, and 30 days after last dose

Population: There are different numbers for overall participants analyzed because we don't have that data available (i.e., a few participants didn't do a baseline questionnaire).

To evaluate the occurrence of symptoms and correlate to disease progression and tolerance to treatment using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). Participants rate their symptoms on a questionnaire using an 11-point scale (0-10) of how much symptoms interfered with different aspects of a patient's life in the last 24 hours such as general activity, mood, work, relations with other people, walking and enjoyment of life. 0 is "not present" and 10 is "as bad as you can imagine." Differences of at least 2 points will be classified as the minimum clinically meaningful change in the symptom severity measures.

Outcome measures

Outcome measures
Measure	Vaccine n=8 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Heat Shock Protein Peptide Complex-96.(HSPPC-96). Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of HSPPC-96 0.4mL intradermal vaccine. HSPPC-96 vaccine will then be given 21 days after the day 5 dose of temozolomide. HSPPC-96 vaccine will be given for 6 cycles or until supply runs out. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Placebo n=8 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Placebo Vaccine. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of placebo vaccine. Placebo vaccine will then be given 21 days after the day 5 dose of temozolomide. Placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Ancillary Treatment n=13 Participants Radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as 30-minute IV infusion every 3 weeks on days 1, 22, and 43. After completion of 6 cycles, participants may continue on Pembrolizumab for an additional 12 months if felt to be of benefit by the treating physician. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Probably Related Adverse events probably related to Pembrolizumab.	Definitely Related Adverse events definitely related to Pembrolizumab.
Mean Symptom Interference Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). Baseline	2.9 Score on a scale Standard Deviation 2.4	1.9 Score on a scale Standard Deviation 1.4	2.2 Score on a scale Standard Deviation 2.7	—	—
Mean Symptom Interference Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). End of treatment or discontinuation	7.0 Score on a scale Standard Deviation 4.0	1.6 Score on a scale Standard Deviation 2.8	4.3 Score on a scale Standard Deviation 4.1	—	—
Mean Symptom Interference Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). 30 days after last dose	—	6.0 Score on a scale	3.1 Score on a scale Standard Deviation 2.9	—	—

SECONDARY outcome

Timeframe: Baseline, end of treatment or discontinuation, and 30 days after last dose

Population: There are different numbers for overall participants analyzed because we don't have that data available (i.e., a few participants didn't do a baseline questionnaire).

Percentage of participants rating their symptom severity to be 5 or greater (on a 0-10) scale using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT). Participants rate their symptoms on a questionnaire using an 11-point scale (0-10). 0 is "not present" and 10 is "as bad as you can imagine."

Outcome measures

Outcome measures
Measure	Vaccine n=8 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Heat Shock Protein Peptide Complex-96.(HSPPC-96). Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of HSPPC-96 0.4mL intradermal vaccine. HSPPC-96 vaccine will then be given 21 days after the day 5 dose of temozolomide. HSPPC-96 vaccine will be given for 6 cycles or until supply runs out. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Placebo n=8 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Placebo Vaccine. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of placebo vaccine. Placebo vaccine will then be given 21 days after the day 5 dose of temozolomide. Placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Ancillary Treatment n=13 Participants Radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as 30-minute IV infusion every 3 weeks on days 1, 22, and 43. After completion of 6 cycles, participants may continue on Pembrolizumab for an additional 12 months if felt to be of benefit by the treating physician. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Probably Related Adverse events probably related to Pembrolizumab.	Definitely Related Adverse events definitely related to Pembrolizumab.
Percentage of Participants Rating Their Symptom Severity to Be 5 or Greater (on a 0-10) Scale Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) Baseline	38 Percentage of participants Interval 9.0 to 76.0	63 Percentage of participants Interval 25.0 to 92.0	54 Percentage of participants Interval 25.0 to 81.0	—	—
Percentage of Participants Rating Their Symptom Severity to Be 5 or Greater (on a 0-10) Scale Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) End of treatment or discontinuation	83 Percentage of participants Interval 36.0 to 100.0	100 Percentage of participants Interval 16.0 to 100.0	83 Percentage of participants Interval 36.0 to 100.0	—	—
Percentage of Participants Rating Their Symptom Severity to Be 5 or Greater (on a 0-10) Scale Using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) 30 days after last dose	—	100 Percentage of participants Interval 29.0 to 100.0	100 Percentage of participants Interval 3.0 to 100.0	—	—

SECONDARY outcome

Timeframe: Time from registration to the time of confirmed progression, an average of 9 months

PFS is defined as the time from registration to the time of confirmed progression. Progression was measured by the immunotherapy response assessment for neuro-oncology (iRANO) criteria. Progressive disease is ≥25% increase in the sum of bi-perpendicular diameters of enhancing disease or new lesions or significant worsened T2/fluid-attenuated inversion recovery (FLAIR) or significant clinical decline.

Outcome measures

Outcome measures
Measure	Vaccine n=8 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Heat Shock Protein Peptide Complex-96.(HSPPC-96). Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of HSPPC-96 0.4mL intradermal vaccine. HSPPC-96 vaccine will then be given 21 days after the day 5 dose of temozolomide. HSPPC-96 vaccine will be given for 6 cycles or until supply runs out. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Placebo n=9 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Placebo Vaccine. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of placebo vaccine. Placebo vaccine will then be given 21 days after the day 5 dose of temozolomide. Placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Ancillary Treatment n=15 Participants Radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as 30-minute IV infusion every 3 weeks on days 1, 22, and 43. After completion of 6 cycles, participants may continue on Pembrolizumab for an additional 12 months if felt to be of benefit by the treating physician. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Probably Related Adverse events probably related to Pembrolizumab.	Definitely Related Adverse events definitely related to Pembrolizumab.
Progression Free Survival (PFS)	13.7 Months Interval 9.92 to The follow-up is not long enough to estimate the upper bound of the confidence intervals for median PFS.	8.0 Months Interval 5.94 to The follow-up is not long enough to estimate the upper bound of the confidence intervals for median PFS.	10.3 Months Interval 5.9 to The follow-up is not long enough to estimate the upper bound of the confidence intervals for median PFS.	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Date treatment consent signed to date off study, approximately 61.5 months.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Vaccine n=8 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Heat Shock Protein Peptide Complex-96.(HSPPC-96). Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of HSPPC-96 0.4mL intradermal vaccine. HSPPC-96 vaccine will then be given 21 days after the day 5 dose of temozolomide. HSPPC-96 vaccine will be given for 6 cycles or until supply runs out. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Placebo n=9 Participants Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Placebo Vaccine. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of placebo vaccine. Placebo vaccine will then be given 21 days after the day 5 dose of temozolomide. Placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Ancillary Treatment n=15 Participants Radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as 30-minute IV infusion every 3 weeks on days 1, 22, and 43. After completion of 6 cycles, participants may continue on Pembrolizumab for an additional 12 months if felt to be of benefit by the treating physician. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Probably Related n=58 Participants Adverse events probably related to Pembrolizumab.	Definitely Related Adverse events definitely related to Pembrolizumab.
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	8 Participants	9 Participants	15 Participants	2 Participants	—

Adverse Events

Vaccine

Serious events: 6 serious events

Other events: 8 other events

Deaths: 6 deaths

Placebo

Serious events: 4 serious events

Other events: 9 other events

Deaths: 4 deaths

Ancillary Treatment

Serious events: 8 serious events

Other events: 12 other events

Deaths: 10 deaths

Enrolled But Not Treated

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Kevin Camphausen

National Cancer Institute

Phone: 240-760-6205

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Vaccine n=8 participants at risk Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Heat Shock Protein Peptide Complex-96.(HSPPC-96). Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of HSPPC-96 0.4mL intradermal vaccine. HSPPC-96 vaccine will then be given 21 days after the day 5 dose of temozolomide. HSPPC-96 vaccine will be given for 6 cycles or until supply runs out. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with HSPPC-96 if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Placebo n=9 participants at risk Radiation therapy (RT)+Temozolomide (TZ)+Pembrolizumab+Placebo Vaccine. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as a 30-minute IV infusion every 3 weeks on days 1, 22, and 43. At one year, if participants are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. One week post RT, patients will receive weekly x 4 a dose of placebo vaccine. Placebo vaccine will then be given 21 days after the day 5 dose of temozolomide. Placebo vaccine will be given for 6 cycles or until supply runs out. Participants who receive placebo will be matched for number of vaccine injections that were generated by their tumor tissue. At one year, if patients are doing well, they may continue pembrolizumab for 12 more months alone or in conjunction with placebo vaccine if any is available. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Ancillary Treatment n=15 participants at risk Radiation therapy (RT) + Temozolomide (TMZ) + Pembrolizumab. Pembrolizumab at 200mg will be administered on day 1 as a 30-minute intravenous (IV) infusion (prior to radiation therapy during RT phase) every 3 weeks on days 1, 22 and 43. Post RT, participants continue on Pembrolizumab 200mg on day 1 as 30-minute IV infusion every 3 weeks on days 1, 22, and 43. After completion of 6 cycles, participants may continue on Pembrolizumab for an additional 12 months if felt to be of benefit by the treating physician. Temozolomide: TMZ will be administered on day 1 of radiation therapy (before RT treatment) and continue throughout RT at the dose of 75 mg/m\^2. Post RT: The starting TMZ dose will be 150 mg/m\^2/day for cycle 1, days 1-5, with a single dose escalation to 200 mg/m\^2/day (days 29-33) and for all subsequent treatment if no treatment-related adverse events greater than Grade 2 are noted. TMZ will be given for 6 cycles.	Enrolled But Not Treated n=58 participants at risk Participants were enrolled but not treated.
Investigations Alanine aminotransferase increased	0.00% 0/8 • Date treatment consent signed to date off study, approximately 61.5 months.	11.1% 1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Injury, poisoning and procedural complications Aspiration	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/15 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, hyponatremia	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/15 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Psychiatric disorders Confusion	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/15 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Investigations Creatinine increased	0.00% 0/8 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Metabolism and nutrition disorders Dehydration	0.00% 0/8 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Gastrointestinal disorders Diarrhea	0.00% 0/8 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
General disorders Disease progression	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/15 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Nervous system disorders Edema cerebral	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Nervous system disorders Encephalopathy	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/15 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
General disorders Fatigue	0.00% 0/8 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/8 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
General disorders Fever	0.00% 0/8 • Date treatment consent signed to date off study, approximately 61.5 months.	11.1% 1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/8 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	13.3% 2/15 • Number of events 3 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Nervous system disorders Headache	12.5% 1/8 • Number of events 3 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Nervous system disorders Hydrocephalus	0.00% 0/8 • Date treatment consent signed to date off study, approximately 61.5 months.	11.1% 1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/15 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/8 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	6.7% 1/15 • Number of events 2 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Vascular disorders Hypertension	0.00% 0/8 • Date treatment consent signed to date off study, approximately 61.5 months.	11.1% 1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/15 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/8 • Date treatment consent signed to date off study, approximately 61.5 months.	11.1% 1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Vascular disorders Hypotension	0.00% 0/8 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	6.7% 1/15 • Number of events 2 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Nervous system disorders Intracranial hemorrhage	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/15 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/15 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Musculoskeletal and connective tissue disorders Muscle weakness right-sided	0.00% 0/8 • Date treatment consent signed to date off study, approximately 61.5 months.	11.1% 1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Gastrointestinal disorders Nausea	0.00% 0/8 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Nervous system disorders Nervous system disorders - Other, altered mental status	0.00% 0/8 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Nervous system disorders Seizure	37.5% 3/8 • Number of events 3 • Date treatment consent signed to date off study, approximately 61.5 months.	22.2% 2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 61.5 months.	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	1.7% 1/58 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.
Infections and infestations Sepsis	0.00% 0/8 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	13.3% 2/15 • Number of events 3 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Cardiac disorders Sinus tachycardia	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/15 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Nervous system disorders Somnolence	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Cardiac disorders Supraventricular tachycardia	0.00% 0/8 • Date treatment consent signed to date off study, approximately 61.5 months.	11.1% 1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/15 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Vascular disorders Thromboembolic event	25.0% 2/8 • Number of events 2 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	13.3% 2/15 • Number of events 2 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Renal and urinary disorders Urinary incontinence	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/15 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Infections and infestations Urinary tract infection	12.5% 1/8 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	13.3% 2/15 • Number of events 2 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Gastrointestinal disorders Vomiting	0.00% 0/8 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/58 • Date treatment consent signed to date off study, approximately 61.5 months.
Nervous system disorders Stroke	0.00% 0/8 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/9 • Date treatment consent signed to date off study, approximately 61.5 months.	0.00% 0/15 • Date treatment consent signed to date off study, approximately 61.5 months.	1.7% 1/58 • Number of events 1 • Date treatment consent signed to date off study, approximately 61.5 months.