Squamous Cell Carcinoma of Head and NeckPhase 2NCT04144517
A Study of ALKS 4230 (Nemvaleukin Alfa) With Pembrolizumab in Head and Neck Cancer
A Phase 2 study testing Nemvaleukin Alfa and Pembrolizumab in people with Squamous Cell Carcinoma of Head and Neck, run by Mural Oncology, Inc at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma of Head and Neck
- What is being tested?
- Nemvaleukin Alfa and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 7 sitesUnited States
- Study dates
- 5 Feb 2020to 7 Jan 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Mural Oncology Investigational Site
Atlanta, Georgia, 30308
Mural Oncology Investigational Site
Austin, Texas, 78712
Mural Oncology Investigational Site
Cleveland, Ohio, 44195
Mural Oncology Investigational Site
Miami, Florida, 33136
Mural Oncology Investigational Site
Minneapolis, Minnesota, 55455
Mural Oncology Investigational Site
New York, New York, 10016
Mural Oncology Investigational Site
New York, New York, 10029
About this study
Official title: 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.
- Conditions
- Squamous Cell Carcinoma of Head and Neck
- Being tested
- Nemvaleukin Alfa, Pembrolizumab
- Keywords
- Alkermes, IL-2, Interleukin-2, Oncology, Immuno-oncology, Cytokine Immunotherapy, ALKS 4230, Pembrolizumab, Keytruda, PD-L1, Solid Tumors
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nemvaleukin AlfaDrug
Nemvaleukin alfa IV infusion.
PembrolizumabDrug
Also called Keytruda
Pembrolizumab IV infusion.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Nemvaleukin 3 mcg/kg + Pembrolizumab 200 mg | Experimental | 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. Receives: Drug: Nemvaleukin Alfa; Drug: Pembrolizumab |
| Group 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Experimental | 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. Receives: Drug: Nemvaleukin Alfa; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From the first dose of study drug until first PD or death, whichever occurred first (up to 49 weeks)
Secondary outcomes (7)
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.
Measured: From first documented CR or PR until first documentation of PD (up to 49 weeks)
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.
Measured: 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
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.
Measured: 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
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).
Measured: From first dose of study drug until PD or death, whichever occurred first (up to 49 weeks)
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.
Measured: 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)
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.
Measured: 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
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.
Measured: From first dose of study drug through 90 days after the last dose of study drug (up to 62 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2019
- Study start5 Feb 2020
- Primary completion8 Oct 2021
- Study completion7 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Squamous Cell Carcinoma of Head and NeckStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mural Oncology, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Immune Oncology Network (ION)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Mural Oncology, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04144517
- Sponsor's protocol ID
- ION-01-ALKS 4230
- Status last verified
- Sep 2024
- First submitted
- 24 Oct 2019
- Last updated
- 16 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04144517
- Acronym / sponsor ID
- ION-01-ALKS 4230
- Conditions
- Squamous Cell Carcinoma of Head and Neck
- Keywords
- Alkermes, IL-2, Interleukin-2, Oncology, Immuno-oncology, Cytokine Immunotherapy, ALKS 4230, Pembrolizumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Mural Oncology, IncIndustry (pharma, biotech, devices)
- Collaborators
- Immune Oncology Network (ION)
- Study start
- 5 Feb 2020 (actual)
- Primary completion
- 8 Oct 2021 (actual)
- Study completion
- 7 Jan 2022 (actual)
- First posted
- 30 Oct 2019 (actual)
- Results
- Posted 16 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1: Nemvaleukin 3 mcg/kg + Pembrolizumab 200 mg | Experimental | Drug: Nemvaleukin Alfa, Drug: PembrolizumabParticipants 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. |
| Group 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg | Experimental | Drug: Nemvaleukin Alfa, Drug: PembrolizumabParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nemvaleukin AlfaNemvaleukin alfa IV infusion. | Drug | Group 1: Nemvaleukin 3 mcg/kg + Pembrolizumab 200 mg, Group 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg |
| PembrolizumabAlso: KeytrudaPembrolizumab IV infusion. | Drug | Group 1: Nemvaleukin 3 mcg/kg + Pembrolizumab 200 mg, Group 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg |
Primary outcome
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.
7 secondary outcomes
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)
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)
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)
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)
Overall Survival (OS)
Time frame: 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)
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Mural Oncology, Inc
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nemvaleukin Alfa and Pembrolizumab in people with Squamous Cell Carcinoma of Head and Neck, run by Mural Oncology, Inc at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2024.