NCT04326257

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

Completed Phase 2 Results posted Last updated 8 January 2026

What this trial tests

Phase 2 trial testing Nivolumab+Relatlimab in Squamous Cell Carcinoma of the Head and Neck in 20 participants. Completed in 12 August 2024.

Timeline

14 May 2020

Primary endpoint
12 August 2023

12 August 2024

Quick facts

Lead sponsor	Dan Zandberg
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	20
Start date	14 May 2020
Primary completion	12 August 2023
Estimated completion	12 August 2024
Sites	1 location across United States

Drugs / interventions tested

• Nivolumab+Relatlimab
• Nivolumab+Ipilimumab

Conditions studied

• Squamous Cell Carcinoma of the Head and Neck — all drugs for Squamous Cell Carcinoma of the Head and Neck →

Sponsor

Dan Zandberg — full company profile →

Who can join

18 and older, any sex, with Squamous Cell Carcinoma of the Head and Neck. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Probability of Objective Response (OR) - Selected Treatment Primary · From start of treatment, up to 36 months

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.

Group	Value	95% CI
Selected Treatment	0

Probability of Objective Response (OR) - Randomized Treatment Secondary · From start of treatment, up to 36 months

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.

Group	Value	95% CI
Randomized Treatment	0

Disease Control Rate (DCR) Secondary · From start of treatment, up to 36 months

The percent probability of not experiencing disease progression in patients regardless of selected/randomized treatment. 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; Stable Disease (SD) is neither sufficient decrease (target lesions) to qualify as a PR or sufficient increase to qualify as PD. Incomplete Response/Stable Disease (SD) is the persistence of one

Group	Value	95% CI
Selected Treatment	33.3	9.7 – 70.0
Randomized Treatment	25.0	8.9 – 53.2

Progression-free Survival (PFS) Secondary · From start of treatment up to 36 months

The length of time from the start of treatment that patients live with disease that does not progress per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) in patients who have progressed on prior immunotherapy. Per RECIST, Progressive Disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions compared to baseline sum of target lesions, or any new lesions.It also includes the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Group	Value	95% CI
Selected Treatment	52.00	31.60 – 72.40
Randomized Treatment	53.00	50.92 – 55.09

Overall Survival (OS) Secondary · From start of treatment, up to 36 months

The length of time from the start of treatment that patients remain alive, in patients who have progressed on prior immunotherapy.

Group	Value	95% CI
Selected Treatment	166.00	22.92 – 309.08
Randomized Treatment	164.00	0.00 – 379.60

Duration of Disease Control Secondary · From start of treatment, up to 36 months

Mean number of months that patients who had Stable Disease experienced disease control. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Stable Disease (SD) is neither sufficient decrease (target lesions) to qualify as a PR or sufficient increase to qualify as PD. Incomplete Response/Stable Disease (SD) is the persistence of one or more non-target lesions.

Group	Value	95% CI
Selected Treatment	133.50	± 122.33
Randomized Treatment	97.67	± 81.82

Adverse Events Per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Secondary · From start of treatment, up to 36 months

Adverse Events possibly, probably or definitely related to study treatment per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 experienced.

Alanine aminotransferase increased

Group	Value	95% CI
Nivolumab+Relatlimab	3
Nivolumab+Ipilimumab	1

Alkaline phosphatase increased

Group	Value	95% CI
Nivolumab+Relatlimab	2
Nivolumab+Ipilimumab	0

Anemia

Group	Value	95% CI
Nivolumab+Relatlimab	2
Nivolumab+Ipilimumab	2

Anorexia

Group	Value	95% CI
Nivolumab+Relatlimab	1
Nivolumab+Ipilimumab	0

Aspartate aminotransferase increased

Group	Value	95% CI
Nivolumab+Relatlimab	3
Nivolumab+Ipilimumab	1

PACs on EKG

Group	Value	95% CI
Nivolumab+Relatlimab	1
Nivolumab+Ipilimumab	0

Cough

Group	Value	95% CI
Nivolumab+Relatlimab	0
Nivolumab+Ipilimumab	1

Creatinine increased

Group	Value	95% CI
Nivolumab+Relatlimab	1
Nivolumab+Ipilimumab	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events data were collected for up to 36 months. All-Cause Mortality data was collected for up to 46 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Nivolumab+Relatlimab

Serious: 11/13 (85%)

Deaths: 12/13

Nivolumab+Ipilimumab

Serious: 6/7 (86%)

Deaths: 4/7

Serious adverse events (126 terms)

Reaction	System	Nivolumab+Relatlimab	Nivolumab+Ipilimumab
Anemia	Blood and lymphatic system disorders	—	—
Fatigue	General disorders	—	—
Hyponatremia	Metabolism and nutrition disorders	—	—
Hyperglycemia	Metabolism and nutrition disorders	—	—
Hypoalbuminemia	Metabolism and nutrition disorders	—	—
Hypothyroidism	Endocrine disorders	—	—
Lymphocyte count decreased	Investigations	—	—
Alanine aminotransferase increased	Investigations	—	—
Constipation	Gastrointestinal disorders	—	—
Hypertension	Vascular disorders	—	—
Hypomagnesemia	Metabolism and nutrition disorders	—	—
Hypophosphatemia	Metabolism and nutrition disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Alkaline phosphatase increased	Investigations	—	—
Aspartate aminotransferase increased	Investigations	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Creatinine increased	Investigations	—	—
Depression	Psychiatric disorders	—	—
Diarrhea	Gastrointestinal disorders	—	—
Dry mouth	Gastrointestinal disorders	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—
Gastroesophageal reflux disease	Gastrointestinal disorders	—	—
Oral pain	Gastrointestinal disorders	—	—
Platelet count decreased	Investigations	—	—
White blood cell decreased	Investigations	—	—

Other adverse events (130 terms — click to expand)

Reaction	System	Nivolumab+Relatlimab	Nivolumab+Ipilimumab
Anemia	Blood and lymphatic system disorders	—	—
Fatigue	General disorders	—	—
Hyponatremia	Metabolism and nutrition disorders	—	—
Hyperglycemia	Metabolism and nutrition disorders	—	—
Hypoalbuminemia	Metabolism and nutrition disorders	—	—
Hypothyroidism	Endocrine disorders	—	—
Lymphocyte count decreased	Investigations	—	—
Alanine aminotransferase increased	Investigations	—	—
Constipation	Gastrointestinal disorders	—	—
Hypertension	Vascular disorders	—	—
Hypomagnesemia	Metabolism and nutrition disorders	—	—
Hypophosphatemia	Metabolism and nutrition disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Alkaline phosphatase increased	Investigations	—	—
Aspartate aminotransferase increased	Investigations	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Creatinine increased	Investigations	—	—
Depression	Psychiatric disorders	—	—
Diarrhea	Gastrointestinal disorders	—	—
Dry mouth	Gastrointestinal disorders	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—
Gastroesophageal reflux disease	Gastrointestinal disorders	—	—
Oral pain	Gastrointestinal disorders	—	—
Platelet count decreased	Investigations	—	—
White blood cell decreased	Investigations	—	—
Anorexia	Metabolism and nutrition disorders	—	—
Anxiety	Psychiatric disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Dysgeusia	Nervous system disorders	—	—
Dysphagia	Gastrointestinal disorders	—	—
Facial pain	General disorders	—	—
Headache	Nervous system disorders	—	—
Hypercalcemia	Metabolism and nutrition disorders	—	—
INR increased	Investigations	—	—
Insomnia	Psychiatric disorders	—	—
Metabolism and nutrition disorders - Other, specifyType II Diabetes	Metabolism and nutrition disorders	—	—
Neck pain	Musculoskeletal and connective tissue disorders	—	—
Pain	General disorders	—	—
Peripheral sensory neuropathy	Nervous system disorders	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—

Most-reported serious reactions: Anemia, Fatigue, Hyponatremia, Hyperglycemia, Hypoalbuminemia, Hypothyroidism, Lymphocyte count decreased, Alanine aminotransferase increased.

Data from ClinicalTrials.gov NCT04326257 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Immune checkpoint modulators in cancer immunotherapy: recent advances and emerging concepts.
   Wang Y, Zhang H, Liu C, Wang Z, et al · · 2022 · cited 179× · PMID 35978433 · DOI 10.1186/s13045-022-01325-0
2. Understanding LAG-3 Signaling.
   Chocarro L, Blanco E, Zuazo M, Arasanz H, et al · · 2021 · cited 154× · PMID 34067904 · DOI 10.3390/ijms22105282
3. The promising immune checkpoint LAG-3 in cancer immunotherapy: from basic research to clinical application.
   Huo JL, Wang YT, Fu WJ, Lu N, et al · · 2022 · cited 124× · PMID 35958563 · DOI 10.3389/fimmu.2022.956090
4. Therapeutic approaches for the treatment of head and neck squamous cell carcinoma-An update on clinical trials.
   Goel B, Tiwari AK, Pandey RK, Singh AP, et al · · 2022 · cited 94× · PMID 35460943 · DOI 10.1016/j.tranon.2022.101426
5. Tumor hypoxia is associated with resistance to PD-1 blockade in squamous cell carcinoma of the head and neck.
   Zandberg DP, Menk AV, Velez M, Normolle D, et al · · 2021 · cited 94× · PMID 33986123 · DOI 10.1136/jitc-2020-002088
6. Clinical Insights Into Novel Immune Checkpoint Inhibitors.
   Lee JB, Ha SJ, Kim HR. · · 2021 · cited 81× · PMID 34025438 · DOI 10.3389/fphar.2021.681320
7. Blockade of novel immune checkpoints and new therapeutic combinations to boost antitumor immunity.
   Archilla-Ortega A, Domuro C, Martin-Liberal J, Muñoz P. · · 2022 · cited 61× · PMID 35164813 · DOI 10.1186/s13046-022-02264-x
8. LAG3 and its emerging role in cancer immunotherapy.
   Wang M, Du Q, Jin J, Wei Y, et al · · 2021 · cited 58× · PMID 33784013 · DOI 10.1002/ctm2.365