Trial Outcomes & Findings for SBRT and Oncolytic Virus Therapy Before Pembrolizumab for Metastatic TNBC and NSCLC (NCT NCT03004183)
NCT ID: NCT03004183
Last Updated: 2024-10-15
Results Overview
The objective response rate (ORR) of ADV/HSV-tk plus (+) valacyclovir therapy in combination with SBRT used as a window of opportunity treatment before pembrolizumab in patients with metastatic TNBC and metastatic NSCLC. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be used to assess treatment response. Modified immune-related response criteria (irRC; derived from RECIST 1.1) will also be documented.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
57 participants
Primary outcome timeframe
30 days after the last dose of pembrolizumab until disease progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. Median duration of follow-up was 8.3 months (95% CI 3.0-10.1 months).
Results posted on
2024-10-15
Participant Flow
57 overall participants (28 TNBC and 29 NSCLS)
The Triple Negative Breast Cancer (TNBC) patients with histologically confirmed locally advanced or metastatic TNBC that has relapsed or is refractory to ≥1 lines of standard of care therapy. The Non-Small Cell Lung Cancer (NSCLC) cohort will include male \& female patients with confirmed metastatic NSCLC that is immunotherapy naïve or previously treated with a maximum of 1 immunotherapy regimen \& chemotherapy naïve or previously treated with 1 cycle of platinum-containing chemotherapy.
Participant milestones
| Measure |
Single Arm
ADV/HSV-tk (5 x 1011 virus particles) in a 2-mL total volume will be injected intratumorally on Day 0.
Valacyclovir will be orally administered at a dose of 2 g three times daily for 14 days from Day 1 to Day 15.
SBRT of 30 Gy (6 Gy X 5 fractions) will be administered over 2 weeks from Day 2 to Day 16.
Pembrolizumab (200 mg) will be administered intravenously over 30 minutes every 3 weeks starting on Day 17 and continuing until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
ADV/HSV-tk: Replication-defective recombinant adenovirus vector
Valacyclovir: Prodrug of the antiviral drug acyclovir
SBRT: Low-dose SBRT
Pembrolizumab: Humanized immunoglobulin G4 anti-programmed death-1 (PD-1) monoclonal antibody
|
|---|---|
|
Overall Study
STARTED
|
57
|
|
Overall Study
TNBC
|
28
|
|
Overall Study
NSCLC
|
29
|
|
Overall Study
COMPLETED
|
7
|
|
Overall Study
NOT COMPLETED
|
50
|
Reasons for withdrawal
| Measure |
Single Arm
ADV/HSV-tk (5 x 1011 virus particles) in a 2-mL total volume will be injected intratumorally on Day 0.
Valacyclovir will be orally administered at a dose of 2 g three times daily for 14 days from Day 1 to Day 15.
SBRT of 30 Gy (6 Gy X 5 fractions) will be administered over 2 weeks from Day 2 to Day 16.
Pembrolizumab (200 mg) will be administered intravenously over 30 minutes every 3 weeks starting on Day 17 and continuing until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
ADV/HSV-tk: Replication-defective recombinant adenovirus vector
Valacyclovir: Prodrug of the antiviral drug acyclovir
SBRT: Low-dose SBRT
Pembrolizumab: Humanized immunoglobulin G4 anti-programmed death-1 (PD-1) monoclonal antibody
|
|---|---|
|
Overall Study
Adverse Event
|
7
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Physician Decision
|
40
|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
COVID-19
|
1
|
Baseline Characteristics
The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
Baseline characteristics by cohort
| Measure |
Single Arm
n=56 Participants
ADV/HSV-tk (5 x 1011 virus particles) in a 2-mL total volume will be injected intratumorally on Day 0.
Valacyclovir will be orally administered at a dose of 2 g three times daily for 14 days from Day 1 to Day 15.
SBRT of 30 Gy (6 Gy X 5 fractions) will be administered over 2 weeks from Day 2 to Day 16.
Pembrolizumab (200 mg) will be administered intravenously over 30 minutes every 3 weeks starting on Day 17 and continuing until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
ADV/HSV-tk: Replication-defective recombinant adenovirus vector
Valacyclovir: Prodrug of the antiviral drug acyclovir
SBRT: Low-dose SBRT
Pembrolizumab: Humanized immunoglobulin G4 anti-programmed death-1 (PD-1) monoclonal antibody
|
|---|---|
|
Age, Categorical
Overall · <=18 years
|
0 Participants
n=56 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Age, Categorical
Overall · Between 18 and 65 years
|
32 Participants
n=56 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Age, Categorical
Overall · >=65 years
|
24 Participants
n=56 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Age, Categorical
TNBC · <=18 years
|
0 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Age, Categorical
TNBC · Between 18 and 65 years
|
24 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Age, Categorical
TNBC · >=65 years
|
4 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Age, Categorical
NSCLC · <=18 years
|
0 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Age, Categorical
NSCLC · Between 18 and 65 years
|
8 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Age, Categorical
NSCLC · >=65 years
|
20 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Sex: Female, Male
Overall · Female
|
40 Participants
n=56 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Sex: Female, Male
Overall · Male
|
16 Participants
n=56 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Sex: Female, Male
TNBC · Female
|
28 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Sex: Female, Male
TNBC · Male
|
0 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Sex: Female, Male
NSCLC · Female
|
12 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Sex: Female, Male
NSCLC · Male
|
16 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Ethnicity (NIH/OMB)
Overall · Hispanic or Latino
|
4 Participants
n=56 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Ethnicity (NIH/OMB)
Overall · Not Hispanic or Latino
|
52 Participants
n=56 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Ethnicity (NIH/OMB)
Overall · Unknown or Not Reported
|
0 Participants
n=56 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Ethnicity (NIH/OMB)
TNBC · Hispanic or Latino
|
3 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Ethnicity (NIH/OMB)
TNBC · Not Hispanic or Latino
|
25 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Ethnicity (NIH/OMB)
TNBC · Unknown or Not Reported
|
0 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Ethnicity (NIH/OMB)
NSCLC · Hispanic or Latino
|
1 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Ethnicity (NIH/OMB)
NSCLC · Not Hispanic or Latino
|
27 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Ethnicity (NIH/OMB)
NSCLC · Unknown or Not Reported
|
0 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Race (NIH/OMB)
Overall · American Indian or Alaska Native
|
0 Participants
n=56 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Race (NIH/OMB)
Overall · Asian
|
6 Participants
n=56 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Race (NIH/OMB)
Overall · Native Hawaiian or Other Pacific Islander
|
0 Participants
n=56 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Race (NIH/OMB)
Overall · Black or African American
|
9 Participants
n=56 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Race (NIH/OMB)
Overall · White
|
41 Participants
n=56 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Race (NIH/OMB)
Overall · More than one race
|
0 Participants
n=56 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Race (NIH/OMB)
Overall · Unknown or Not Reported
|
0 Participants
n=56 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Race (NIH/OMB)
TNBC · American Indian or Alaska Native
|
0 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Race (NIH/OMB)
TNBC · Asian
|
5 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Race (NIH/OMB)
TNBC · Native Hawaiian or Other Pacific Islander
|
0 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Race (NIH/OMB)
TNBC · Black or African American
|
5 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Race (NIH/OMB)
TNBC · White
|
18 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Race (NIH/OMB)
TNBC · More than one race
|
0 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Race (NIH/OMB)
TNBC · Unknown or Not Reported
|
0 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Race (NIH/OMB)
NSCLC · American Indian or Alaska Native
|
0 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Race (NIH/OMB)
NSCLC · Asian
|
1 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Race (NIH/OMB)
NSCLC · Native Hawaiian or Other Pacific Islander
|
0 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Race (NIH/OMB)
NSCLC · Black or African American
|
4 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Race (NIH/OMB)
NSCLC · White
|
23 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Race (NIH/OMB)
NSCLC · More than one race
|
0 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
Race (NIH/OMB)
NSCLC · Unknown or Not Reported
|
0 Participants
n=28 Participants • The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
|
|
TNBC and NSCLC patient distribution
TNBC
|
28 Participants
n=56 Participants
|
|
TNBC and NSCLC patient distribution
NSLC
|
28 Participants
n=56 Participants
|
PRIMARY outcome
Timeframe: 30 days after the last dose of pembrolizumab until disease progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. Median duration of follow-up was 8.3 months (95% CI 3.0-10.1 months).Population: A total of 56 patient's data was analyzed, 28 patients with mTNBC and 28 patients with NSCLC.
The objective response rate (ORR) of ADV/HSV-tk plus (+) valacyclovir therapy in combination with SBRT used as a window of opportunity treatment before pembrolizumab in patients with metastatic TNBC and metastatic NSCLC. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be used to assess treatment response. Modified immune-related response criteria (irRC; derived from RECIST 1.1) will also be documented.
Outcome measures
| Measure |
Single Arm
n=56 Participants
ADV/HSV-tk (5 x 1011 virus particles) in a 2-mL total volume will be injected intratumorally on Day 0.
Valacyclovir will be orally administered at a dose of 2 g three times daily for 14 days from Day 1 to Day 15.
SBRT of 30 Gy (6 Gy X 5 fractions) will be administered over 2 weeks from Day 2 to Day 16.
Pembrolizumab (200 mg) will be administered intravenously over 30 minutes every 3 weeks starting on Day 17 and continuing until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
ADV/HSV-tk: Replication-defective recombinant adenovirus vector
Valacyclovir: Prodrug of the antiviral drug acyclovir
SBRT: Low-dose SBRT
Pembrolizumab: Humanized immunoglobulin G4 anti-programmed death-1 (PD-1) monoclonal antibody
|
|---|---|
|
Objective Response Rate
Overall · Complete Response
|
4 Participants
|
|
Objective Response Rate
Overall · Partial Response
|
7 Participants
|
|
Objective Response Rate
Overall · Stable Diseases
|
13 Participants
|
|
Objective Response Rate
Overall · Progressive Disease
|
32 Participants
|
|
Objective Response Rate
TNBC · Complete Response
|
2 Participants
|
|
Objective Response Rate
TNBC · Partial Response
|
1 Participants
|
|
Objective Response Rate
TNBC · Stable Diseases
|
3 Participants
|
|
Objective Response Rate
TNBC · Progressive Disease
|
22 Participants
|
|
Objective Response Rate
NSCLC · Complete Response
|
2 Participants
|
|
Objective Response Rate
NSCLC · Partial Response
|
6 Participants
|
|
Objective Response Rate
NSCLC · Stable Diseases
|
10 Participants
|
|
Objective Response Rate
NSCLC · Progressive Disease
|
10 Participants
|
SECONDARY outcome
Timeframe: 30 days after the last dose of pembrolizumab until disease progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. Median duration of follow-up was 8.3 months (95% CI 3.0-10.1 months).Population: Median duration of response from last line of treatment (range), months
Duration of response to ADV/HSV-tk plus valacyclovir therapy in combination with SBRT followed by pembrolizumab
Outcome measures
| Measure |
Single Arm
n=56 Participants
ADV/HSV-tk (5 x 1011 virus particles) in a 2-mL total volume will be injected intratumorally on Day 0.
Valacyclovir will be orally administered at a dose of 2 g three times daily for 14 days from Day 1 to Day 15.
SBRT of 30 Gy (6 Gy X 5 fractions) will be administered over 2 weeks from Day 2 to Day 16.
Pembrolizumab (200 mg) will be administered intravenously over 30 minutes every 3 weeks starting on Day 17 and continuing until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
ADV/HSV-tk: Replication-defective recombinant adenovirus vector
Valacyclovir: Prodrug of the antiviral drug acyclovir
SBRT: Low-dose SBRT
Pembrolizumab: Humanized immunoglobulin G4 anti-programmed death-1 (PD-1) monoclonal antibody
|
|---|---|
|
Duration of Response
TNBC
|
2 Months
Interval 1.0 to 7.0
|
|
Duration of Response
NSCLC
|
5.5 Months
Interval 0.0 to 13.0
|
SECONDARY outcome
Timeframe: After confirmed disease progression or starts a new therapy, the subject moves into the Survival Follow-up to be contacted every 12 weeks to assess for survival status until death, withdrawal, or end of study. Median duration of follow-up was 8.3 months.Population: Median overall survival for all patient and for patients with clinical benefit
Overall survival (OS) rate in subjects receiving ADV/HSV-tk plus valacyclovir therapy in combination with SBRT followed by pembrolizumab. OS is the time (measured in months) from intratumoral viral injection to death or last date of contact.
Outcome measures
| Measure |
Single Arm
n=56 Participants
ADV/HSV-tk (5 x 1011 virus particles) in a 2-mL total volume will be injected intratumorally on Day 0.
Valacyclovir will be orally administered at a dose of 2 g three times daily for 14 days from Day 1 to Day 15.
SBRT of 30 Gy (6 Gy X 5 fractions) will be administered over 2 weeks from Day 2 to Day 16.
Pembrolizumab (200 mg) will be administered intravenously over 30 minutes every 3 weeks starting on Day 17 and continuing until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
ADV/HSV-tk: Replication-defective recombinant adenovirus vector
Valacyclovir: Prodrug of the antiviral drug acyclovir
SBRT: Low-dose SBRT
Pembrolizumab: Humanized immunoglobulin G4 anti-programmed death-1 (PD-1) monoclonal antibody
|
|---|---|
|
Overall Survival Rate
TNBC
|
6.6 Months
Interval 0.0 to 50.0
|
|
Overall Survival Rate
NSCLC
|
12.9 Months
Interval 0.0 to 32.0
|
SECONDARY outcome
Timeframe: Adverse Events (AEs) and Serious Adverse Events (SAEs) will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab, (up to 24 months of treatment for patients without disease progression).Population: The results are distributed based on a total of 56 patients, 28 TNBC and 28 NSCLC evaluable patients.
To document the toxicities associated with ADV/HSV-tk + valacyclovir therapy in combination with SBRT used as a window of opportunity treatment before pembrolizumab in patients with metastatic TNBC and metastatic NSCLC. Toxicity will be defined as the number of participants with any treatment-related death or any ≥ Grade 3 hematological toxicity excluding alopecia and constitutional symptoms, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03.
Outcome measures
| Measure |
Single Arm
n=56 Participants
ADV/HSV-tk (5 x 1011 virus particles) in a 2-mL total volume will be injected intratumorally on Day 0.
Valacyclovir will be orally administered at a dose of 2 g three times daily for 14 days from Day 1 to Day 15.
SBRT of 30 Gy (6 Gy X 5 fractions) will be administered over 2 weeks from Day 2 to Day 16.
Pembrolizumab (200 mg) will be administered intravenously over 30 minutes every 3 weeks starting on Day 17 and continuing until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
ADV/HSV-tk: Replication-defective recombinant adenovirus vector
Valacyclovir: Prodrug of the antiviral drug acyclovir
SBRT: Low-dose SBRT
Pembrolizumab: Humanized immunoglobulin G4 anti-programmed death-1 (PD-1) monoclonal antibody
|
|---|---|
|
Number of Participants With Treatment-related Adverse Events
Total with Related SAE
|
2 Participants
|
|
Number of Participants With Treatment-related Adverse Events
TNBC
|
2 Participants
|
|
Number of Participants With Treatment-related Adverse Events
NSCLC
|
0 Participants
|
SECONDARY outcome
Timeframe: 30 days after the last dose of pembrolizumabPopulation: At this point in the data analysis has not been completed, information will be updated as it becomes available.
Measure the antitumor activity as assessed by RECIST 1.1. Modified immune-related response criteria will also be documented.
Outcome measures
| Measure |
Single Arm
n=56 Participants
ADV/HSV-tk (5 x 1011 virus particles) in a 2-mL total volume will be injected intratumorally on Day 0.
Valacyclovir will be orally administered at a dose of 2 g three times daily for 14 days from Day 1 to Day 15.
SBRT of 30 Gy (6 Gy X 5 fractions) will be administered over 2 weeks from Day 2 to Day 16.
Pembrolizumab (200 mg) will be administered intravenously over 30 minutes every 3 weeks starting on Day 17 and continuing until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
ADV/HSV-tk: Replication-defective recombinant adenovirus vector
Valacyclovir: Prodrug of the antiviral drug acyclovir
SBRT: Low-dose SBRT
Pembrolizumab: Humanized immunoglobulin G4 anti-programmed death-1 (PD-1) monoclonal antibody
|
|---|---|
|
Antitumor Activity
Overall · Complete Response
|
4 Participants
|
|
Antitumor Activity
Overall · Partial Response
|
7 Participants
|
|
Antitumor Activity
Overall · Stable Diseases
|
13 Participants
|
|
Antitumor Activity
Overall · Progressive Disease
|
32 Participants
|
|
Antitumor Activity
TNBC · Complete Response
|
2 Participants
|
|
Antitumor Activity
TNBC · Partial Response
|
1 Participants
|
|
Antitumor Activity
TNBC · Stable Diseases
|
3 Participants
|
|
Antitumor Activity
TNBC · Progressive Disease
|
22 Participants
|
|
Antitumor Activity
NSCLS · Complete Response
|
2 Participants
|
|
Antitumor Activity
NSCLS · Partial Response
|
6 Participants
|
|
Antitumor Activity
NSCLS · Stable Diseases
|
10 Participants
|
|
Antitumor Activity
NSCLS · Progressive Disease
|
10 Participants
|
SECONDARY outcome
Timeframe: 30 days after the last dose of pembrolizumab until disease progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. Median duration of follow-up was 8.3 months (95% CI 3.0-10.1 months).Population: The Clinical Benefit Rate measured as Complete Response plus Partial Response plus Stable Disease
Clinical benefit rate of ADV/HSV-tk plus valacyclovir therapy in combination with SBRT followed by pembrolizumab
Outcome measures
| Measure |
Single Arm
n=56 Participants
ADV/HSV-tk (5 x 1011 virus particles) in a 2-mL total volume will be injected intratumorally on Day 0.
Valacyclovir will be orally administered at a dose of 2 g three times daily for 14 days from Day 1 to Day 15.
SBRT of 30 Gy (6 Gy X 5 fractions) will be administered over 2 weeks from Day 2 to Day 16.
Pembrolizumab (200 mg) will be administered intravenously over 30 minutes every 3 weeks starting on Day 17 and continuing until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
ADV/HSV-tk: Replication-defective recombinant adenovirus vector
Valacyclovir: Prodrug of the antiviral drug acyclovir
SBRT: Low-dose SBRT
Pembrolizumab: Humanized immunoglobulin G4 anti-programmed death-1 (PD-1) monoclonal antibody
|
|---|---|
|
Clinical Benefit Rate
Overall
|
24 Participants
|
|
Clinical Benefit Rate
TNBC
|
6 Participants
|
|
Clinical Benefit Rate
NSCLC
|
18 Participants
|
SECONDARY outcome
Timeframe: 30 days after the last dose of pembrolizumab until disease progression, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up.Population: Median duration of progression free response from last line of treatment (range), months
To determine the progression-free survival (PFS) of ADV/HSV-tk + valacyclovir therapy in combination with SBRT used as a window of opportunity treatment before pembrolizumab in patients with metastatic TNBC and metastatic NSCLC as measured in months and defined the number of months a patient remains free from disease progression.
Outcome measures
| Measure |
Single Arm
n=56 Participants
ADV/HSV-tk (5 x 1011 virus particles) in a 2-mL total volume will be injected intratumorally on Day 0.
Valacyclovir will be orally administered at a dose of 2 g three times daily for 14 days from Day 1 to Day 15.
SBRT of 30 Gy (6 Gy X 5 fractions) will be administered over 2 weeks from Day 2 to Day 16.
Pembrolizumab (200 mg) will be administered intravenously over 30 minutes every 3 weeks starting on Day 17 and continuing until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
ADV/HSV-tk: Replication-defective recombinant adenovirus vector
Valacyclovir: Prodrug of the antiviral drug acyclovir
SBRT: Low-dose SBRT
Pembrolizumab: Humanized immunoglobulin G4 anti-programmed death-1 (PD-1) monoclonal antibody
|
|---|---|
|
Progression-free Survival in Months
TNBC
|
2.5298 months
Interval 1.05 to 48.53
|
|
Progression-free Survival in Months
NSCLC
|
7.4 months
Interval 5.1 to 9.6
|
OTHER_PRE_SPECIFIED outcome
Timeframe: baseline and 30 days after the last dose of pembrolizumabMeasure the computed tomography-based response (RECIST 1.1) of a non-target lesion to ADV/HSV-tk plus valacyclovir therapy in combination with SBRT followed by pembrolizumab
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: baseline and 30 days after the last dose of pembrolizumabMeasure the change in immunohistochemical expression of tumor-infiltrating lymphocytes in tumor biopsy tissues in response to ADV/HSV-tk plus valacyclovir therapy in combination with SBRT followed by pembrolizumab
Outcome measures
Outcome data not reported
Adverse Events
Single Arm
Serious events: 29 serious events
Other events: 28 other events
Deaths: 17 deaths
Serious adverse events
| Measure |
Single Arm
n=56 participants at risk
ADV/HSV-tk (5 x 1011 virus particles) in a 2-mL total volume will be injected intratumorally on Day 0.
Valacyclovir will be orally administered at a dose of 2 g three times daily for 14 days from Day 1 to Day 15.
SBRT of 30 Gy (6 Gy X 5 fractions) will be administered over 2 weeks from Day 2 to Day 16.
Pembrolizumab (200 mg) will be administered intravenously over 30 minutes every 3 weeks starting on Day 17 and continuing until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
ADV/HSV-tk: Replication-defective recombinant adenovirus vector
Valacyclovir: Prodrug of the antiviral drug acyclovir
SBRT: Low-dose SBRT
Pembrolizumab: Humanized immunoglobulin G4 anti-programmed death-1 (PD-1) monoclonal antibody
|
|---|---|
|
Musculoskeletal and connective tissue disorders
Intractable pain, back pain, hip pain
|
5.4%
3/56 • Number of events 4 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
|
Blood and lymphatic system disorders
Anemia
|
1.8%
1/56 • Number of events 1 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.8%
1/56 • Number of events 2 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
|
Cardiac disorders
Atrial fibrillation with rapid ventricular response
|
3.6%
2/56 • Number of events 2 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
|
Gastrointestinal disorders
Abdominal pain
|
5.4%
3/56 • Number of events 4 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
|
Gastrointestinal disorders
colitis
|
1.8%
1/56 • Number of events 1 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
|
Metabolism and nutrition disorders
Malnutrition, Hypercalcemia and Weakness
|
5.4%
3/56 • Number of events 4 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
|
Renal and urinary disorders
Kidney Injury and/or Infection
|
7.1%
4/56 • Number of events 6 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
5.4%
3/56 • Number of events 3 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
|
Respiratory, thoracic and mediastinal disorders
Shortness of Breath
|
8.9%
5/56 • Number of events 5 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
7.1%
4/56 • Number of events 4 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
3.6%
2/56 • Number of events 4 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.8%
1/56 • Number of events 2 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
|
Skin and subcutaneous tissue disorders
Skin rash
|
1.8%
1/56 • Number of events 2 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
Other adverse events
| Measure |
Single Arm
n=56 participants at risk
ADV/HSV-tk (5 x 1011 virus particles) in a 2-mL total volume will be injected intratumorally on Day 0.
Valacyclovir will be orally administered at a dose of 2 g three times daily for 14 days from Day 1 to Day 15.
SBRT of 30 Gy (6 Gy X 5 fractions) will be administered over 2 weeks from Day 2 to Day 16.
Pembrolizumab (200 mg) will be administered intravenously over 30 minutes every 3 weeks starting on Day 17 and continuing until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
ADV/HSV-tk: Replication-defective recombinant adenovirus vector
Valacyclovir: Prodrug of the antiviral drug acyclovir
SBRT: Low-dose SBRT
Pembrolizumab: Humanized immunoglobulin G4 anti-programmed death-1 (PD-1) monoclonal antibody
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
8.9%
5/56 • Number of events 5 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
|
Gastrointestinal disorders
Abdominal pain
|
8.9%
5/56 • Number of events 5 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
|
Gastrointestinal disorders
Diarrhea
|
8.9%
5/56 • Number of events 5 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
|
Gastrointestinal disorders
Nausea
|
12.5%
7/56 • Number of events 7 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
|
General disorders
Fatigue
|
21.4%
12/56 • Number of events 12 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
|
Investigations
Activated partial thromboplastin time prolonged
|
5.4%
3/56 • Number of events 10 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
|
Investigations
Weight Loss
|
7.1%
4/56 • Number of events 4 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.7%
6/56 • Number of events 6 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
7.1%
4/56 • Number of events 5 • AEs and SAEs will be captured from the time of informed consent signing up to 30 days after the final dose of pembrolizumab. Study treatment-related SAEs and any study patient death occurring beyond 30 days after the last dose of pembrolizumab should also be reported. Patients will be treated until disease progression, unacceptable toxicity, or up to 24 months in subjects without disease progression.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place