Ramucirumab and Pembrolizumab vs Pembrolizumab Monotherapy in PD-L1 Positive Head and Neck Squamous-Cell Carcinoma

NCT05980000 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 202308161
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 2 study investigating the efficacy of ramucirumab in combination with pembrolizumab compared to pembrolizumab monotherapy. Ramucirumab is a VEGFR-2 inhibitor believed to potentially enhance the efficacy of PD-1 inhibitors such as pembrolizumab.

Conditions

Recurrent Head and Neck Cancer; Recurrent Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Carcinoma; Metastatic Head-and-neck Squamous-cell Carcinoma; Metastatic Head and Neck Cancer; HNSCC

Keywords

PD-L1 positive RM-HNSCC; RM-HNSCC; oral cavity HNSCC; oropharynx HNSCC; larynx HNSCC; hypopharynx HNSCC

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as the number of patients with a complete response (CR) and a partial response (PR) by RECIST 1.1 criteria. A CR is defined as the disappearance of all target lesions, reduction in pathological lymph nodes to \<10 mm in short axis, and disappearance of all non-target lesions with normalization of tumor marker level. A PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  From start of study treatment through completion of treatment (estimated to be 24 months)

Secondary Outcomes (4)

• Duration of Response (DoR)

  From time criteria is met for CR or PR through completion of treatment (estimated to be 1 year and 40 weeks)

• Progression-Free Survival (PFS)

  From start of study treatment through 5 years

• Overall Survival (OS)

  From start of study treatment through 5 years

• Incidence rate, frequency, and severity of adverse events (AEs)

  From start of study treatment through 30 days after last dose (expected to be 2 years and 1 month)

Study Arms (2)

Arm 1: Ramucirumab and Pembrolizumab

EXPERIMENTAL

Patients receive ramucirumab IV and pembrolizumab IV every 3 weeks. Cycles are 21 days in length. Treatment will continue until progression or unacceptable toxicity for up to 35 cycles of treatment.

Drug: Ramucirumab; Drug: Pembrolizumab

Arm 2: Pembrolizumab monotherapy

ACTIVE COMPARATOR

Patients receive pembrolizumab IV every 3 weeks. Cycles are 21 days in length. Treatment will continue until progression or unacceptable toxicity for up to 35 cycles of treatment.

Drug: Pembrolizumab

Interventions

Ramucirumab DRUG

Ramucirumab is administered at a dose of 10 mg/kg over 60 minutes.

Also known as: Cyramza

Arm 1: Ramucirumab and Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab is administered at a flat dose of 200 mg over 30 minutes.

Also known as: MK-3475, Keytruda

Arm 1: Ramucirumab and Pembrolizumab; Arm 2: Pembrolizumab monotherapy

Eligibility Criteria

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

You may qualify if:

• Incurable RM-HNSCC, defined as RM disease or second or subsequent primary HNSCC not amenable to cure by surgery and/or radiation therapy or patient declines or is ineligible for curative therapy. Eligible primary tumor sub-sites include oral cavity, oropharynx, larynx and hypopharynx only.
• PD-L1 positive (CPS ≥1) disease, based on local IHC assay using 22C3 antibody.
• Measurable disease per RECIST 1.1.
• No prior systemic therapy for RM-HNSCC. RM disease developing within 6 months of completion of either a) systemic platinum or cetuximab therapy given as a component of a curative-intent multi-modality regimen or b) radiation therapy and/or surgery is eligible.
• At least 18 years of age.
• ECOG performance status 0-1.
• Normal bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1.5 K/cumm
• Platelets ≥ 100 K/cumm
• Hemoglobin ≥ 9.0 g/dL
• Total bilirubin ≤ 1.5 x IULN
• AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN. In the setting of liver metastases, AST(SGOT)/ALT(SGPT) ≤ 5.0 x IULN
• Creatinine ≤ 1.5 x ULN. If patient has creatinine \> 1.5 x ULN, then 24 hour urine collection must be performed and creatinine clearance must be ≥ 40 mL/min by Cockcroft-Gault
• Urine protein to creatinine ratio (UPC) ≤ 1; if UPC \> 1, then a 24-hour urine protein must be assessed and patient must have a 24-hour urine protein value \< 1 g to be eligible
• INR ≤ 1.5 (≤ 3.0 if on warfarin) and PTT ≤ 1.5 x ULN (Patients are allowed to be on anticoagulation)

You may not qualify if:

• PD-L1 negative (CPS 0) disease, based on local IHC assay using 22C3 antibody.
• Cutaneous or nasopharynx SCC.
• Major surgery within 28 days prior to C1D1, minor surgery or subcutaneous venous access device placement within 7 days prior to C1D1, history of significant tumor site bleeding within 14 days prior to C1D1, or elective or planned major surgery to be performed during the course of the clinical trial.
• Palliative radiation therapy within 2 weeks of C1D1.
• Serious or non-healing, non-malignant wound, ulcer, or bone fracture within 28 days prior to C1D1.
• A history of other malignancy ≤ 1 year previous with the exception of completely resected skin carcinoma or other cancers with a low risk (\<10%) of recurrence over the next 2 years.
• Cirrhosis at a level of Child-Pugh B (or worse). Cirrhosis of any degree with a history of hepatic encephalopathy or clinically meaningful ascites (from cirrhosis requiring diuretics or paracentesis).
• Currently receiving any other investigational agents.
• Ongoing toxicity attributed to prior anti-cancer therapy that is \> grade 1, except alopecia, anemia, lymphopenia, xerostomia, fatigue or rash.
• Active central nervous system metastases: defined as currently receiving radiation therapy to metastatic CNS disease. Once radiation therapy is completed and patient has completed a 2 week washout, patients with CNS disease are eligible if they meet all other criteria for enrollment.
• A history of severe allergic reactions attributed to compounds of similar chemical or biologic composition to Ramucirumab or other agents used in the study.
• Serious uncontrolled intercurrent illness within the 3 months prior to study entry including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, or cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements.
• Receiving systemic corticosteroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of intense immunosuppressive therapy within 7 days prior to C1D1.
• Active autoimmune disease (i.e. rheumatoid arthritis, lupus) that has required IV or subcutaneous systemic treatment in the past 6 months prior to C1D1 (excluding Rituxan). Replacement therapy (i.e. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• GI perforation or fistula within 6 months of C1D1. Malignant oral fistulas are not excluded.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Ramucirumab; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

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

Study Officials

• Douglas R Adkins, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be randomized on a 2:1 basis to Arm 1 or Arm 2.

Study Record Dates

• First Submitted: July 30, 2023
• First Posted: August 7, 2023
• Study Start: October 27, 2023
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2030
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)