A Study of ALKS 4230 (Nemvaleukin Alfa) With Pembrolizumab in Head and Neck Cancer

Study Overview
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Brief Summary
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The primary objective of this study is to estimate the response rate to ALKS 4230 in combination with pembrolizumab in patients with HNSCC who have previously received anti-PD-(L)1 therapy but who have not achieved a CR.

Official Title
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A Phase 2 Study of ALKS 4230 in Combination With Anti-PD-1 (Pembrolizumab) in Patients With Advanced or Recurrent Head and Neck Squamous Cell Cancer Currently on Treatment With Anti-PD-(L)1 Without Having Achieved a Complete Remission

Conditions
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Non-cutaneous Squamous Cell Carcinoma of Head and Neck

Intervention / Treatment
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* Drug: ALKS 4230
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALKS 4230 + pembrolizumab<br> | Drug: ALKS 4230<br>* Intravenous (IV) infusion over 30 minutes given daily for 5 consecutive days followed by an off-treatment period<br>Drug: Pembrolizumab<br>* IV infusion over 30 minutes administered on Day 1 of each cycle<br>* Other names: Keytruda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with objective evidence of improvement to partial response among those patients who had stable disease at baseline on prior anti-PD-(L)1 therapy | Response will be based on investigator review of radiographic and/or photographic images and RECIST criteria v1.1 | From time of initiation of therapy until the date of first documented tumor progression, assessed up to 12 months | 
| Proportion of patients with objective evidence of improvement to complete response among those patients who had stable disease or partial response at baseline on prior anti-PD-(L)1 therapy | Response will be based on investigator review of radiographic and/or photographic images and RECIST criteria v1.1 | From time of initiation of therapy until the date of first documented tumor progression, assessed up to 12 months | 
| Proportion of patients with objective evidence of improvement to partial response among those patients who had disease progression at baseline on prior anti-PD-(L)1 therapy | Response will be based on investigator review of radiographic and/or photographic images and RECIST criteria v1.1 | From time of initiation of therapy until the date of first documented tumor progression, assessed up to 12 months | 
| Proportion of patients with objective evidence of improvement to complete response among those patients who had disease progression at baseline on prior anti-PD-(L)1 therapy | Response will be based on investigator review of radiographic and/or photographic images and RECIST criteria v1.1 | From time of initiation of therapy until the date of first documented tumor progression, assessed up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response in subjects with CR or PR |  | Time from the first documentation of complete response or partial response, measured approximately every 6 weeks, to the first documentation of objective tumor progression or death due to any cause (estimated up to 24 months) | 
| Progression-free survival (PFS) |  | Time from first dose of study drug to the time of first documentation of objective tumor progression or death due to any cause (estimated up to 24 months) | 
| Time to progression |  | Time from first dose of study drug to the time of first documentation of objective tumor progression or death due to disease progression (estimated up to 24 months) | 
| Rate of non-progression (ie, disease control rate) at 6 months |  | Assessed PFS at 6 months | 
| Overall survival |  | Time from first dose of study drug to the time of death (estimated up to 24 months) | 
| Incidence of drug-related AEs |  | Time from first dose of study drug to the end of study (up to 36 months) | 
| Incidence of drug-related SAEs |  | Time from first dose of study drug to the end of study (up to 36 months) | 
| Incidence of drug-related AEs leading to discontinuation |  | Time from first dose of study drug to the end of study (up to 36 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alkermes, IL-2, Interleukin-2, Oncology, Immuno-oncology, Cytokine Immunotherapy, ALKS 4230, Pembrolizumab, Keytruda, PD-L1, Solid Tumors