Personalized Immunotherapy in Patients With Recurrent /Metastatic SCCHN That Have Progressed on Prior Immunotherapy

NCT04326257 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: HCC 18-156
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

In this Phase II trial of personalized immunotherapy in R/M HNSCC, gene expression of LAG3 and CTLA4 by RNA seq will be determined to select the appropriate agent (Ipilimumab or Relatlimab) to add to Nivolumab in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M HNSCC) who have failed prior immunotherapy with anti-PD-1 or PD-L1 mAb therapy. The agent, either Ipilimumab or Relatlimab will be chosen based on the highest relevant immune gene expression (CTLA4 or LAG-3) as long as the minimum difference required is met.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Keywords

nivolumab; Relatlimab; Ipilimumab; immunotherapy; anti-PD-1; anti-PD-L1; RECIST 1.1; recurrent cancer; metastatic cancer; tumor microenvironment analysis; LAG-3; CTLA-4

Outcome Measures

Primary Outcomes (1)

• Probability of Objective Response (OR) - Selected Treatment

  The probability of response to therapy in patients who have progressed on prior immunotherapy. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Complete Response (CR) is disappearance of all target and non-target lesions; Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  From start of treatment, up to 36 months

Secondary Outcomes (6)

• Probability of Objective Response (OR) - Randomized Treatment

  From start of treatment, up to 36 months

• Disease Control Rate (DCR)

  From start of treatment, up to 36 months

• Progression-free Survival (PFS)

  From start of treatment up to 36 months

• Overall Survival (OS)

  From start of treatment, up to 36 months

• Duration of Disease Control

  From start of treatment, up to 36 months

Study Arms (2)

Nivolumab+Relatlimab

EXPERIMENTAL

Nivolumab will be dosed 480mg IV q 4 weeks and Relatlimab 160mg IV q 4 weeks One cycle is defined as 4 weeks of treatment and both drugs are given on the same day. Patients will receive the prescribed therapy continuously for up to 24 cycles until progression of disease or adverse event(s) requiring treatment discontinuation.

Drug: Nivolumab+Relatlimab

Nivolumab+Ipilimumab

EXPERIMENTAL

Nivolumab will be dosed at 3mg/kg IV q 2 weeks and Ipilimumab 1mg/kg IV q 6 weeks. Patients will receive four doses of Ipilimumab and the last dosage of Nivolumab 3mg/kg IV q 2 weeks will be given at the time of the 4th dose of Ipilimumab, followed 2 weeks later by Nivolumab 480 mg IV q 4 weeks. A cycle of therapy will be defined as 4 weeks of treatment. The patient will receive the prescribed therapy continuously for up to 24 cycles until progression of disease or adverse event(s) requiring treatment discontinuation.

Drug: Nivolumab+Ipilimumab

Interventions

Nivolumab+Relatlimab DRUG

IV administration of both Nivolumab and Relatlimab

Also known as: Nivolumab: OPDIVO/ BMS-936558/ MDX1106/ ONO-4538;, Relatlimab: BMS-986016

Nivolumab+Relatlimab

Nivolumab+Ipilimumab DRUG

IV administration of both Nivolumab and Ipilimumab

Also known as: Nivolumab: OPDIVO/ BMS-936558/ MDX1106/ ONO-4538, Ipilimumab: YERVOY/ BMS-734016/ MDX-010

Nivolumab+Ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Recurrent and/or Metastatic squamous cell carcinoma of the head and neck that is not amenable to therapy with curative intent. Patients who refuse salvage surgery or radiation for recurrence are potentially eligible.
• Failure of prior immunotherapy as defined as:
• Progression of disease on anti-PD-1 mAb or anti-PD-L1 mAb treatment in the R/M setting.
• Both patients that have received platinum based chemotherapy prior or have not yet received platinum based chemotherapy are eligible.
• Patients cannot have received more than 3 total lines of prior systemic therapy in the recurrent/metastatic setting.
• ECOG performance status of 0-1
• Have at least one measurable area of disease (Target Lesion) based on RECIST 1.1.
• Provide adequate tissue (core or incisional/excisional biopsy) prior to starting study for analysis for gene expression of LAG3 and CTLA4 per OmniSeq Immune Report Card. FNA is not adequate. Archival tissue can only be used if it was obtained in the recurrent/metastatic setting and there has been no subsequent cancer treatment after that tissue was obtained.
• Life expectancy of at least 12 weeks based on investigator estimate.
• Age ≥ 18 years old
• LVEF assessment with documented LVEF ≥50% by either TTE or MUGA (TTE preferred test) within 6 months from first study drug administration
• Patients must have normal organ and marrow function as defined below:
• absolute neutrophil count ≥1,500/mcL
• platelets ≥100,000/mcL
• total bilirubin ≤ institutional upper limit of normal (ULN)

You may not qualify if:

• SCC of salivary gland origin or cutaneous SCC of the head and neck. HNSCC of unknown origin ARE eligible.
• Patients who received Ipilimumab or Relatlimab in the recurrent/metastatic setting will be excluded.
• Is currently participating in or has participated in a study of an investigational agent or used an investigational device within 2 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (equivalent of \>10 mg of prednisone) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has had a prior monoclonal antibody, chemotherapy, or targeted small molecule therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier (alopecia is an exception). Note: Subjects with ≤ Grade 2 neuropathy, ototoxicity, hypothyroidism or hyperthyroidism, are an exception to this criterion and qualify for the study.
• History of other malignancy within 3 years with the exception of prior HNSCC, adequately treated basal cell or squamous cell skin cancer, or carcinoma of the cervix.
• Has an active autoimmune disease requiring systemic immunosuppressive treatment within the past 3 months. Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic therapy or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
• Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:
• Myocardial infarction (MI) or stroke/transient ischemic attack (TIA) within the 6 months prior to consent;
• Uncontrolled angina within the 3 months prior to consent;
• Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, torsades de pointes, or poorly controlled atrial fibrillation);
• QTc prolongation \> 480 msec;
• History of other clinically significant cardiovascular disease (i.e., cardiomyopathy, congestive heart failure with New York Heart Association \[NYHA\] functional classification III-IV, pericarditis, significant pericardial effusion, significant coronary stent occlusion, poorly controlled deep venous thrombosis, etc.);
• Cardiovascular disease-related requirement for daily supplemental oxygen
• History of two or more MIs OR two or more coronary revascularization procedures

Sponsors & Collaborators

• Dan Zandberg: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Recurrence; Neoplasm Metastasis; Diabetes Mellitus, Insulin-Dependent, 12

Interventions

Opdualag; Nivolumab; relatlimab; Ipilimumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Barbara Stadterman, MPH, CCRP
• Organization: UPMC

stadtermanbm@upmc.edu

7245532539

Study Officials

• Dan P Zandberg, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Head and Neck and Thyroid Cancer Disease Sections and Co-Director, UPMC Hillman Cancer Center Head and Neck Cancer Research Program

Model Details: In this open-label, 2 parallel arms trial, RNA seq analysis via the Omniseq immune report card will be used to determine which drug (Relatlimab or Ipilimumab) will be added to Nivolumab for treatment.

Study Record Dates

• First Submitted: March 25, 2020
• First Posted: March 30, 2020
• Study Start: May 14, 2020
• Primary Completion: August 12, 2023
• Study Completion: August 12, 2024
• Last Updated: January 8, 2026
• Results First Posted: January 8, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)