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

September 24, 2024 updated by: Mural Oncology, Inc

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33136
        • Mural Oncology Investigational Site
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Mural Oncology Investigational Site
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Mural Oncology Investigational Site
    • New York
      • New York, New York, United States, 10016
        • Mural Oncology Investigational Site
      • New York, New York, United States, 10029
        • Mural Oncology Investigational Site
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Mural Oncology Investigational Site
    • Texas
      • Austin, Texas, United States, 78712
        • Mural Oncology Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group 1: Nemvaleukin 3 mcg/kg + Pembrolizumab 200 mg
Participants with current stable disease (SD) or partial response (PR) (Cohorts 1 and 2) who were not progressing or further demonstrating reductions in tumor size were to receive nemvaleukin alfa 3 microgram per kilogram (mcg/kg), intravenous (IV) infusion, daily from Days 1 to 5 of the first week of each 3-week treatment cycle in combination with pembrolizumab 200 milligram (mg), IV infusion, once, every three weeks (Q3W) on Day 1 of each 21-day cycle until confirmed progression, unacceptable toxicity or met other criteria for discontinuation.
Drug: Pembrolizumab
Pembrolizumab IV infusion.
Other Names:
  • Keytruda
Drug: Nemvaleukin Alfa
Nemvaleukin alfa IV infusion.
Experimental: Group 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Participants with progressive disease (PD) (Cohorts 3 and 4) 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.
Drug: Pembrolizumab
Pembrolizumab IV infusion.
Other Names:
  • Keytruda
Drug: Nemvaleukin Alfa
Nemvaleukin alfa IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR) Based on RECIST v1.1
Time Frame: 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.
From the first dose of study drug until first PD or death, whichever occurred first (up to 49 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Response (DOR) Based on RECIST v1.1
Time Frame: 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.
From first documented CR or PR until first documentation of PD (up to 49 weeks)
Progression-free Survival (PFS) Based on RECIST v1.1
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)
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.
From the first dose of study drug to date of PD, start of alternate therapy or death, whichever occurred first (up to 49 weeks)
Time to Progression (TTP) Based on RECIST v1.1
Time Frame: 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.
From first dose of study drug to the date of the first documentation of PD (up to 49 weeks)
Disease Control Rate (DCR) Based on RECIST v1.1
Time Frame: 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).
From first dose of study drug until PD or death, whichever occurred first (up to 49 weeks)
Overall Survival (OS)
Time Frame: 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.
From date of first dose of study drug up to death from any cause (up to 89 weeks)
Number of Participants With Drug-related Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: 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.
From the first dose of study drug through 90 days after the last dose of study drug (up to 62 weeks)
Number of Participants With Drug-related TEAEs Leading to Discontinuation of Treatment
Time Frame: 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.
From first dose of study drug through 90 days after the last dose of study drug (up to 62 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mural Oncology, Inc

Collaborators

Immune Oncology Network (ION)

Investigators

  • Study Director: Medical Director, Mural Oncology, Inc

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 5, 2020

Primary Completion (Actual)

October 8, 2021

Study Completion (Actual)

January 7, 2022

Study Registration Dates

First Submitted

October 24, 2019

First Submitted That Met QC Criteria

October 28, 2019

First Posted (Actual)

October 30, 2019

Study Record Updates

Last Update Posted (Actual)

October 16, 2024

Last Update Submitted That Met QC Criteria

September 24, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ION-01-ALKS 4230

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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