Trial Outcomes & Findings for Birinapant and Intensity Modulated Re-Irradiation Therapy in Treating Patients With Locally Recurrent Head and Neck Squamous Cell Carcinoma (NCT NCT03803774)

Last Updated: 2025-11-10

Results Overview

Adverse events will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. A DLT is defined as any of the following adverse events possibly attributed to the combination of birinapant and radiotherapy that occur within 42 days after treatment. Any grade 5 toxicities. Any grade ≥ 4 hematologic toxicity, except lymphopenia. Any grade ≥ 3 non-hematologic toxicity except for nausea or vomiting managed with supportive care over 2 weeks. ≥ grade 3 prolonged (\> 7 days) serum amylase or lipase elevation, aspartate aminotransferase elevation, and/or alanine aminotransferase elevation. Any grade toxicity that mandates discontinuation of birinapant treatment for more than 2 weeks. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE1

Target enrollment

13 participants

Primary outcome timeframe

Up to 42 days post-treatment

Results posted on

2025-11-10

Participant Flow

Participant milestones

Participant milestones
Measure	Birinapant 5.6 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) SG1 Dose Level 1 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL 1: Cycle 1-2 Birinapant 5.6 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 11 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) SG1 Dose Level 2 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL 2: Cycle 1-2 Birinapant 11 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 17 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) SG1 Dose Level 3 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL 3: Cycle 1-2 Birinapant 17 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 24 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) SG1 Dose Level Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). Cycle 1-2 Birinapant 24 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)
Dose Escalation STARTED	3	3	4	3
Dose Escalation COMPLETED	3	3	3	3
Dose Escalation NOT COMPLETED	0	0	1	0
Dose Expansion STARTED	0	0	0	0
Dose Expansion COMPLETED	0	0	0	0
Dose Expansion NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Birinapant 2.8 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) SG1 Dose Level -1 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL -1: Cycle 1-2 Birinapant 2.8 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 5.6 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) SG1 Dose Level 1 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL 1: Cycle 1-2 Birinapant 5.6 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 11 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) SG1 Dose Level 2 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL 2: Cycle 1-2 Birinapant 11 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 17 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) SG1 Dose Level 3 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL 3: Cycle 1-2 Birinapant 17 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 24 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) SG1 Dose Level Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). Cycle 1-2 Birinapant 24 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)
Dose Escalation Withdrawal by Subject	0	0	0	1	0

Baseline Characteristics

Birinapant and Intensity Modulated Re-Irradiation Therapy in Treating Patients With Locally Recurrent Head and Neck Squamous Cell Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Birinapant 5.6 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) n=3 Participants SG1 Dose Level 1 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL 1: Cycle 1-2 Birinapant 5.6 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 11 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) n=3 Participants SG1 Dose Level 2 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL 2: Cycle 1-2 Birinapant 11 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 17 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) n=4 Participants SG1 Dose Level 3 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL 3: Cycle 1-2 Birinapant 17 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 24 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) n=3 Participants SG1 Dose Level Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). Cycle 1-2 Birinapant 24 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Total n=13 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants	0 Participants n=28 Participants	0 Participants n=46 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	3 Participants n=20 Participants	3 Participants n=40 Participants	1 Participants n=28 Participants	10 Participants n=46 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=20 Participants	1 Participants n=40 Participants	2 Participants n=28 Participants	3 Participants n=46 Participants
Age, Continuous	51.33 years n=5 Participants	55.67 years n=20 Participants	63 years n=40 Participants	71 years n=28 Participants	60.46 years n=46 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants	1 Participants n=28 Participants	2 Participants n=46 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=20 Participants	4 Participants n=40 Participants	2 Participants n=28 Participants	11 Participants n=46 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=20 Participants	1 Participants n=40 Participants	0 Participants n=28 Participants	2 Participants n=46 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	1 Participants n=20 Participants	2 Participants n=40 Participants	3 Participants n=28 Participants	9 Participants n=46 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=20 Participants	1 Participants n=40 Participants	0 Participants n=28 Participants	2 Participants n=46 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants	0 Participants n=28 Participants	0 Participants n=46 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants	0 Participants n=28 Participants	0 Participants n=46 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=20 Participants	0 Participants n=40 Participants	0 Participants n=28 Participants	1 Participants n=46 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants	0 Participants n=28 Participants	1 Participants n=46 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	1 Participants n=20 Participants	3 Participants n=40 Participants	3 Participants n=28 Participants	9 Participants n=46 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants	0 Participants n=28 Participants	0 Participants n=46 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=20 Participants	1 Participants n=40 Participants	0 Participants n=28 Participants	2 Participants n=46 Participants
Region of Enrollment United States	3 participants n=5 Participants	3 participants n=20 Participants	4 participants n=40 Participants	3 participants n=28 Participants	13 participants n=46 Participants

PRIMARY outcome

Timeframe: Up to 42 days post-treatment

Outcome measures

Outcome measures
Measure	Birinapant 5.6 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) n=3 Participants SG1 Dose Level 1 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL 1: Cycle 1-2 Birinapant 5.6 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 11 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) n=3 Participants SG1 Dose Level 2 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL 2: Cycle 1-2 Birinapant 11 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 17 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) n=4 Participants SG1 Dose Level 3 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL 3: Cycle 1-2 Birinapant 17 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 24 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) n=3 Participants SG1 Dose Level Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). Cycle 1-2 Birinapant 24 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)
Incidence of Dose-limiting Toxicities (DLTs) and Grades 1-5 Serious and/or Non-serious Toxicities Related (Except for Unrelated and Unlikely) to Intervention Grades 1-5 Dose Limiting Toxicities	0 toxicities	0 toxicities	0 toxicities	0 toxicities
Incidence of Dose-limiting Toxicities (DLTs) and Grades 1-5 Serious and/or Non-serious Toxicities Related (Except for Unrelated and Unlikely) to Intervention All serious and non-serious Grades 1-5 related adverse events	66 toxicities	49 toxicities	26 toxicities	1 toxicities
Incidence of Dose-limiting Toxicities (DLTs) and Grades 1-5 Serious and/or Non-serious Toxicities Related (Except for Unrelated and Unlikely) to Intervention All serious Grades 1-5 related adverse events	2 toxicities	2 toxicities	0 toxicities	1 toxicities
Incidence of Dose-limiting Toxicities (DLTs) and Grades 1-5 Serious and/or Non-serious Toxicities Related (Except for Unrelated and Unlikely) to Intervention Grades 3-5 serious and non-serious related adverse events	8 toxicities	6 toxicities	3 toxicities	1 toxicities

PRIMARY outcome

Timeframe: Up to 42 days

MTD is defined as the dose level at which no more than 1 of up to 6 participants experience dose limiting- toxicity (DLT) during 42 days after the start of therapy, and the dose below that at which at least 2 (of =\< 6) participants have DLT as a result of the drug. A DLT is defined as any of the following adverse events possibly attributed to the combination of birinapant and radiotherapy that occur within 42 days after treatment. Any grade 5 toxicities. Any grade ≥ 4 hematologic toxicity except lymphopenia. Any grade ≥ 3 non-hematologic toxicity except for nausea or vomiting managed with supportive care over 2 weeks. ≥ grade 3 prolonged (\> 7 days) serum amylase or lipase elevation, aspartate aminotransferase elevation, and/or alanine aminotransferase elevation. Any grade toxicity that mandates discontinuation of birinapant treatment for more than 2 weeks. Adverse events were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Outcome measures

Outcome measures
Measure	Birinapant 5.6 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) n=13 Participants SG1 Dose Level 1 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL 1: Cycle 1-2 Birinapant 5.6 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 11 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) SG1 Dose Level 2 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL 2: Cycle 1-2 Birinapant 11 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 17 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) SG1 Dose Level 3 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL 3: Cycle 1-2 Birinapant 17 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 24 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) SG1 Dose Level Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). Cycle 1-2 Birinapant 24 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)
Maximum Tolerated Dose (MTD) of Birinapant	24 mg/m^2	—	—	—

SECONDARY outcome

Timeframe: From the start of the treatment until response assessment by positron emission tomography (PET)-computed tomography (CT), assessed at 3 months post-treatment

Overall response is the best response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Estimates of response rates will be determined at the maximum tolerated dose (MTD) level, including the expansion cohort and will be presented along with a 95% two-sided confidence interval. Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesion. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions; and the appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 24 months post-treatment

Estimates of local control will be determined at the maximum tolerated dose (MTD) level, including the expansion cohort and will be presented along with a 95% two-sided confidence interval.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From start of treatment to time of progression or death, whichever occurs first, assessed up to 24 months post-treatment

PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Estimates of PFS will be determined at the maximum tolerated dose (MTD) level, including the expansion cohort and will be presented along with a 95% two-sided confidence interval. Response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions; and the appearance of one or more new lesions.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 24 months post-treatment

OS is the time between the first day of treatment to the day of death. Estimates of OS will be determined at the maximum tolerated dose (MTD) level, including the expansion cohort, and will be presented along with a 95% two-sided confidence interval.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline

The association between FADD copy gain in tumor tissue and/or in blood will be evaluated for any association with response.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline

BIRC2 copy gain in tumor tissue and/or in blood will be evaluated for any association with response.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At baseline

Baculoviral inhibitor of apoptosis (IAP) Repeat containing 2 and Baculoviral IAP Repeat containing 2/3 (BIRC2/3) copy gain in tumor tissue and/or in blood.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to cycle 1, day 4

Will determine the feasibility of detecting effects of birinapant and re-irradiation on pilot pharmacodynamic markers in tumor tissue.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to cycle 1, day 4

Will determine the feasibility of detecting effects of birinapant and re-irradiation on pilot pharmacodynamic markers microwestern for decrease in drug targets IAP1/2.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to cycle 1, day 4

A change (i.e., increase) in apoptosis/necroptosis marker caspase 3 will be evaluated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to cycle 1, day 4

A change (i.e., increase) in apoptosis/necroptosis marker mixed lineage kinase domain-like (MLKL) levels will be evaluated.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: An average of 611 days.

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	Birinapant 5.6 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) n=3 Participants SG1 Dose Level 1 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL 1: Cycle 1-2 Birinapant 5.6 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 11 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) n=3 Participants SG1 Dose Level 2 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL 2: Cycle 1-2 Birinapant 11 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 17 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) n=4 Participants SG1 Dose Level 3 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL 3: Cycle 1-2 Birinapant 17 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 24 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) n=3 Participants SG1 Dose Level Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). Cycle 1-2 Birinapant 24 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	3 Participants	3 Participants	3 Participants	2 Participants

Adverse Events

Birinapant 5.6 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy)

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Birinapant 11 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy)

Serious events: 3 serious events

Other events: 3 other events

Deaths: 1 deaths

Birinapant 17 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy)

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Birinapant 24 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy)

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Vassiliki Saloura

National Cancer Institute

Phone: 240-760-6352

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Birinapant 5.6 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) n=3 participants at risk SG1 Dose Level 1 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL 1: Cycle 1-2 Birinapant 5.6 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 11 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) n=3 participants at risk SG1 Dose Level 2 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL 2: Cycle 1-2 Birinapant 11 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 17 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) n=4 participants at risk SG1 Dose Level 3 Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). LEVEL 3: Cycle 1-2 Birinapant 17 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)	Birinapant 24 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) n=3 participants at risk SG1 Dose Level Dose Escalation: Up to 24 participants with locally recurrent head and neck squamous cell carcinoma (HNSCC) to determine maximum tolerated dose (MTD) (dose escalation group). Cycle 1-2 Birinapant 24 mg/m\^2 intravenous (IV) days 2 \& 9; intensity modulated re-irradiation therapy (IMRRT) 2 Gray (Gy) Fx day(d)1-5 every week (QW) for 3 weeks (wk)
Cardiac disorders Aortic valve disease	0.00% 0/3 • An average of 611 days.	0.00% 0/3 • An average of 611 days.	25.0% 1/4 • Number of events 1 • An average of 611 days.	0.00% 0/3 • An average of 611 days.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/3 • An average of 611 days.	33.3% 1/3 • Number of events 1 • An average of 611 days.	0.00% 0/4 • An average of 611 days.	0.00% 0/3 • An average of 611 days.
Cardiac disorders Cardiac arrest	0.00% 0/3 • An average of 611 days.	33.3% 1/3 • Number of events 1 • An average of 611 days.	0.00% 0/4 • An average of 611 days.	0.00% 0/3 • An average of 611 days.
Metabolism and nutrition disorders Dehydration	33.3% 1/3 • Number of events 2 • An average of 611 days.	0.00% 0/3 • An average of 611 days.	0.00% 0/4 • An average of 611 days.	0.00% 0/3 • An average of 611 days.
Metabolism and nutrition disorders Hyponatremia	33.3% 1/3 • Number of events 1 • An average of 611 days.	0.00% 0/3 • An average of 611 days.	0.00% 0/4 • An average of 611 days.	0.00% 0/3 • An average of 611 days.
Vascular disorders Hypotension	33.3% 1/3 • Number of events 1 • An average of 611 days.	0.00% 0/3 • An average of 611 days.	0.00% 0/4 • An average of 611 days.	0.00% 0/3 • An average of 611 days.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, Iron deficiency anemia	0.00% 0/3 • An average of 611 days.	0.00% 0/3 • An average of 611 days.	0.00% 0/4 • An average of 611 days.	33.3% 1/3 • Number of events 1 • An average of 611 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Progressive disease	33.3% 1/3 • Number of events 1 • An average of 611 days.	0.00% 0/3 • An average of 611 days.	0.00% 0/4 • An average of 611 days.	0.00% 0/3 • An average of 611 days.
Gastrointestinal disorders Pharyngeal stenosis	0.00% 0/3 • An average of 611 days.	0.00% 0/3 • An average of 611 days.	0.00% 0/4 • An average of 611 days.	33.3% 1/3 • Number of events 1 • An average of 611 days.
Nervous system disorders Presyncope	33.3% 1/3 • Number of events 1 • An average of 611 days.	0.00% 0/3 • An average of 611 days.	0.00% 0/4 • An average of 611 days.	0.00% 0/3 • An average of 611 days.
Nervous system disorders Syncope	0.00% 0/3 • An average of 611 days.	33.3% 1/3 • Number of events 1 • An average of 611 days.	25.0% 1/4 • Number of events 1 • An average of 611 days.	0.00% 0/3 • An average of 611 days.
Musculoskeletal and connective tissue disorders Trismus	0.00% 0/3 • An average of 611 days.	33.3% 1/3 • Number of events 1 • An average of 611 days.	0.00% 0/4 • An average of 611 days.	0.00% 0/3 • An average of 611 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.00% 0/3 • An average of 611 days.	33.3% 1/3 • Number of events 2 • An average of 611 days.	0.00% 0/4 • An average of 611 days.	0.00% 0/3 • An average of 611 days.
Vascular disorders Vascular disorders - Other, Carotid Occlusion	0.00% 0/3 • An average of 611 days.	33.3% 1/3 • Number of events 1 • An average of 611 days.	0.00% 0/4 • An average of 611 days.	0.00% 0/3 • An average of 611 days.
Investigations Weight loss	33.3% 1/3 • Number of events 1 • An average of 611 days.	0.00% 0/3 • An average of 611 days.	0.00% 0/4 • An average of 611 days.	0.00% 0/3 • An average of 611 days.