Squamous Cell Carcinoma of Head and Neck
Conditions
Keywords
Alkermes, IL-2, Interleukin-2, Oncology, Immuno-oncology, Cytokine Immunotherapy, ALKS 4230, Pembrolizumab, Keytruda, PD-L1, Solid Tumors
Brief summary
The primary objective of this study was to estimate the response rate to ALKS 4230 in combination with pembrolizumab in patients with HNSCC who had previously received anti-PD-(L)1 therapy but who had not achieved a CR.
Interventions
DRUGNemvaleukin Alfa
Nemvaleukin alfa IV infusion.
DRUGPembrolizumab
Pembrolizumab IV infusion.
Sponsors
Immune Oncology Network (ION)
Mural Oncology, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have histologically or cytopathologically confirmed diagnosis of non-cutaneous squamous cell carcinoma of the head and neck region that is locally advanced and/or recurrent and no longer amenable to local surgical or radiation therapy and/or with evidence of distant metastatic disease * Patients must have had anti-PD-(L)1 therapy as the most recent systemic therapy with either stable disease or partial response on prior anti-PD-(L)1 therapy, or progressive disease on prior anti-PD-(L)1 therapy * Patients must have disease that is measurable by RECIST v1.1 * Patients must be willing to provide tumor tissue biopsy * Patients must demonstrate adequate organ function * Female patients of childbearing potential should have a negative pregnancy test within 72 hours prior to receiving the first dose of study medication * Patients must agree to follow contraceptive requirements defined in the protocol * Additional criteria apply
Exclusion criteria
* Patient is pregnant or breastfeeding or expecting to conceive or father children * Patient has an active major infection requiring systemic therapy within 1 week of starting study drug * Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate, provided that they are stable, have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to study drug * Patient has hypersensitivity to pembrolizumab, ALKS 4230, or any of their excipients * Patient has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (inhaled or topical steroids and steroid replacement at physiologic doses are allowable) * Patient has prior Grade ≥3 immune-related toxicities requiring systemic immunosuppressant treatment that were attributable or possibly attributable to PD-1 immune checkpoint blockade * Patient has active tuberculosis or known active infection with hepatitis B or hepatitis C * Patient has known psychiatric or substance abuse disorders or a social situation that would interfere with cooperation with the requirements of the study * Additional criteria apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) Based on RECIST v1.1 | From the first dose of study drug until first PD or death, whichever occurred first (up to 49 weeks) | ORR was defined as percentage of participants with complete response (CR) or PR as assessed by investigator based on response evaluation criteria in solid tumors (RECIST) version (v) 1.1. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis less than (\<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) Based on RECIST v1.1 | From the first dose of study drug to date of PD, start of alternate therapy or death, whichever occurred first (up to 49 weeks) | PFS was defined as the time (in months) from the date of first dose of study drug to the date of first documentation of objective tumor progression, start of alternate therapy or death due to any cause, whichever occurred first, based on RECIST v1.1. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the baseline SOD of target lesions. |
| Time to Progression (TTP) Based on RECIST v1.1 | From first dose of study drug to the date of the first documentation of PD (up to 49 weeks) | TTP was defined as the time from the date of first dose of study drug to the date of first documentation of PD based on RECIST 1.1. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the baseline SOD of target lesions. |
| Disease Control Rate (DCR) Based on RECIST v1.1 | From first dose of study drug until PD or death, whichever occurred first (up to 49 weeks) | DCR was defined as percentage participants with a confirmed CR, PR, or SD as assessed by an investigator based on RECIST v1.1. CR: disappearance of all target lesions. All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to \<10 mm. PR: at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (this includes baseline sum if that is the smallest on study). |
| Duration of Response (DOR) Based on RECIST v1.1 | From first documented CR or PR until first documentation of PD (up to 49 weeks) | DOR was defined as time in months from the first documentation CR or PR until the first documentation of confirmed PD as assessed by investigator based on RECIST v1.1. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. |
| Number of Participants With Drug-related Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From the first dose of study drug through 90 days after the last dose of study drug (up to 62 weeks) | An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant who was administered a pharmaceutical product. A SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required participant's hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, led to a congenital anomaly/birth defect. TEAE included AE that occurred or worsen after the first dose of study drug. The assessment of the relationship of study drug to TEAEs and SAEs was done by the Investigator (or designated sub-Investigator) according to their best clinical judgment. |
| Number of Participants With Drug-related TEAEs Leading to Discontinuation of Treatment | From first dose of study drug through 90 days after the last dose of study drug (up to 62 weeks) | An AE was any untoward medical occurrence in a participant or clinical investigation participant who was administered a pharmaceutical product. TEAE included AE that occurred or worsen after the first dose of study drug. The assessment of the relationship of study drug to AEs was done by the Investigator (or designated sub-Investigator) according to their best clinical judgment. |
| Overall Survival (OS) | From date of first dose of study drug up to death from any cause (up to 89 weeks) | OS was defined as the time from the date of the first dose of study drug until the date of death due to any cause. Participants were followed for survival after the last dose of study drug. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 7 investigative sites in the United States.
Pre-assignment details
This study consisted of Group 1 (Cohorts 1 and 2) and Group 2 (Cohorts 3 and 4). Group 1 was closed due to lack of recruitment of eligible participants and therefore, no data for Group 1 (Cohorts 1 and 2) were collected, analyzed or reported. Data was collected and analyzed for Group 2 and is presented in this results report.
Participants by arm
| Arm | Count |
|---|---|
| Group 2, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg Participants with advanced, recurrent and/or metastatic squamous cell carcinoma of the HNSCC and with PD with no prior response to \>=8 weeks anti-PD-(L)1) therapy received nemvaleukin alfa 3 mcg/kg, IV infusion, daily from Days 1 to 5 of the first week of each 3-week treatment cycle in combination with pembrolizumab 200 mg, IV infusion, once, Q3W on Day 1 of each 21-day cycle until confirmed progression, unacceptable toxicity or met other criteria for discontinuation. | 8 |
| Group 2, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg Participants with advanced, recurrent and/or metastatic HNSCC and with current PD after prior achievement of best response SD or PR and after \>=8 on weeks on anti-PD-(L)1 therapy received nemvaleukin alfa 3 mcg/kg, IV infusion, daily from Days 1 to 5 of the first week of each 3-week treatment cycle in combination with pembrolizumab 200 mg, IV infusion, once, Q3W on Day 1 of each 21-day cycle until confirmed progression, unacceptable toxicity or met other criteria for discontinuation. | 6 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 6 | 3 |
| Overall Study | Other | 2 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | Group 2, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Total | Group 2, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg |
|---|---|---|---|
| Age, Continuous | 62.3 years STANDARD_DEVIATION 8.62 | 62.3 years STANDARD_DEVIATION 12.36 | 62.3 years STANDARD_DEVIATION 15.19 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 12 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 14 Participants | 8 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 5 Participants | 12 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 8 | 3 / 6 |
| other Total, other adverse events | 8 / 8 | 6 / 6 |
| serious Total, serious adverse events | 4 / 8 | 2 / 6 |
Outcome results
Primary
Overall Response Rate (ORR) Based on RECIST v1.1
ORR was defined as percentage of participants with complete response (CR) or PR as assessed by investigator based on response evaluation criteria in solid tumors (RECIST) version (v) 1.1. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis less than (\<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameter (SOD) of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Time frame: From the first dose of study drug until first PD or death, whichever occurred first (up to 49 weeks)
Population: Efficacy evaluable population included all participants who received at least one dose of both study drugs (nemvaleukin alfa or pembrolizumab) and had measurable disease at post-baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 2, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Overall Response Rate (ORR) Based on RECIST v1.1 | 0 percentage of participants |
| Group 2, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Overall Response Rate (ORR) Based on RECIST v1.1 | 16.7 percentage of participants |
Secondary
Disease Control Rate (DCR) Based on RECIST v1.1
DCR was defined as percentage participants with a confirmed CR, PR, or SD as assessed by an investigator based on RECIST v1.1. CR: disappearance of all target lesions. All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to \<10 mm. PR: at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (this includes baseline sum if that is the smallest on study).
Time frame: From first dose of study drug until PD or death, whichever occurred first (up to 49 weeks)
Population: Efficacy evaluable population included all participants who received at least one dose of both study drugs (nemvaleukin alfa or pembrolizumab) and had measurable disease at post-baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 2, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Disease Control Rate (DCR) Based on RECIST v1.1 | 12.5 percentage of participants |
| Group 2, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Disease Control Rate (DCR) Based on RECIST v1.1 | 83.3 percentage of participants |
Secondary
Duration of Response (DOR) Based on RECIST v1.1
DOR was defined as time in months from the first documentation CR or PR until the first documentation of confirmed PD as assessed by investigator based on RECIST v1.1. CR: disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis \<10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Time frame: From first documented CR or PR until first documentation of PD (up to 49 weeks)
Population: Efficacy evaluable population included all participants who received at least one dose of both study drugs (nemvaleukin alfa or pembrolizumab) and had measurable disease at post-baseline. Here, 'overall number of participants analyzed' signifies participants who had CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Duration of Response (DOR) Based on RECIST v1.1 | NA months |
Secondary
Number of Participants With Drug-related TEAEs Leading to Discontinuation of Treatment
An AE was any untoward medical occurrence in a participant or clinical investigation participant who was administered a pharmaceutical product. TEAE included AE that occurred or worsen after the first dose of study drug. The assessment of the relationship of study drug to AEs was done by the Investigator (or designated sub-Investigator) according to their best clinical judgment.
Time frame: From first dose of study drug through 90 days after the last dose of study drug (up to 62 weeks)
Population: Safety population included participants who received at least one dose of either study drug (nemvaleukin alfa or pembrolizumab).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 2, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Number of Participants With Drug-related TEAEs Leading to Discontinuation of Treatment | Participants With Drug-related TEAEs Leading to Discontinuation of Nemvaleukin Alfa | 3 Participants |
| Group 2, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Number of Participants With Drug-related TEAEs Leading to Discontinuation of Treatment | Participants With Drug-related TEAEs Leading to Discontinuation of Pembrolizumab | 3 Participants |
| Group 2, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Number of Participants With Drug-related TEAEs Leading to Discontinuation of Treatment | Participants With Drug-related TEAEs Leading to Discontinuation of Nemvaleukin Alfa | 0 Participants |
| Group 2, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Number of Participants With Drug-related TEAEs Leading to Discontinuation of Treatment | Participants With Drug-related TEAEs Leading to Discontinuation of Pembrolizumab | 0 Participants |
Secondary
Number of Participants With Drug-related Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant who was administered a pharmaceutical product. A SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required participant's hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, led to a congenital anomaly/birth defect. TEAE included AE that occurred or worsen after the first dose of study drug. The assessment of the relationship of study drug to TEAEs and SAEs was done by the Investigator (or designated sub-Investigator) according to their best clinical judgment.
Time frame: From the first dose of study drug through 90 days after the last dose of study drug (up to 62 weeks)
Population: Safety population included participants who received at least one dose of either study drug (nemvaleukin alfa or pembrolizumab).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 2, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Number of Participants With Drug-related Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Nemvaleukin Alfa Related TEAEs | 6 Participants |
| Group 2, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Number of Participants With Drug-related Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Pembrolizumab Related TEAEs | 4 Participants |
| Group 2, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Number of Participants With Drug-related Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Nemvaleukin Alfa Related SAEs | 0 Participants |
| Group 2, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Number of Participants With Drug-related Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Pembrolizumab Related SAEs | 0 Participants |
| Group 2, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Number of Participants With Drug-related Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Pembrolizumab Related SAEs | 1 Participants |
| Group 2, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Number of Participants With Drug-related Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Nemvaleukin Alfa Related TEAEs | 4 Participants |
| Group 2, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Number of Participants With Drug-related Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Nemvaleukin Alfa Related SAEs | 1 Participants |
| Group 2, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Number of Participants With Drug-related Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Pembrolizumab Related TEAEs | 4 Participants |
Secondary
Overall Survival (OS)
OS was defined as the time from the date of the first dose of study drug until the date of death due to any cause. Participants were followed for survival after the last dose of study drug.
Time frame: From date of first dose of study drug up to death from any cause (up to 89 weeks)
Population: Efficacy evaluable population included all participants who received at least one dose of both study drugs (nemvaleukin alfa or pembrolizumab) and had measurable disease at post-baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Overall Survival (OS) | 5.4 months |
| Group 2, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Overall Survival (OS) | NA months |
Secondary
Progression-free Survival (PFS) Based on RECIST v1.1
PFS was defined as the time (in months) from the date of first dose of study drug to the date of first documentation of objective tumor progression, start of alternate therapy or death due to any cause, whichever occurred first, based on RECIST v1.1. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the baseline SOD of target lesions.
Time frame: From the first dose of study drug to date of PD, start of alternate therapy or death, whichever occurred first (up to 49 weeks)
Population: Efficacy evaluable population included all participants who received at least one dose of both study drugs (nemvaleukin alfa or pembrolizumab) and had measurable disease at post-baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Progression-free Survival (PFS) Based on RECIST v1.1 | 1.3 months |
| Group 2, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Progression-free Survival (PFS) Based on RECIST v1.1 | NA months |
Secondary
Time to Progression (TTP) Based on RECIST v1.1
TTP was defined as the time from the date of first dose of study drug to the date of first documentation of PD based on RECIST 1.1. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the baseline SOD of target lesions.
Time frame: From first dose of study drug to the date of the first documentation of PD (up to 49 weeks)
Population: Efficacy evaluable population included all participants who received at least one dose of both study drugs (nemvaleukin alfa or pembrolizumab) and had measurable disease at post-baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 2, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Time to Progression (TTP) Based on RECIST v1.1 | 1.3 months |
| Group 2, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Time to Progression (TTP) Based on RECIST v1.1 | NA months |