Ramucirumab + Pembrolizumab in Patients With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

NCT03650764 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 201809094
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesize that inhibition of angiogenesis and PD-1 will be more effective than inhibition of PD-1 alone. The first step in pursuing proof of this hypothesis is to establish the safety and feasibility of combining ramucirumab with pembrolizumab, therefore the first part of this protocol is a de-escalation phase I trial of the combination of ramucirumab + pembrolizumab. The key objective of the phase I trial is to establish the safety and the recommended phase 2 dose (RP2D) of ramucirumab for this novel combination regimen in patients with recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC). The second step in pursuing proof of this hypothesis is to establish the efficacy of ramucirumab (using the RP2D) with pembrolizumab. The second part of this protocol is a single arm phase II trial combining ramucirumab + pembrolizumab. The primary objective of the phase II trial is to determine the tumor response rates (complete response (CR) and partial response (PR)) of the treatment combination given as first line therapy in patients with RM-HNSCC.

Conditions

Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Recommended phase 2 dose (RP2D) of ramucirumab combined with fixed dose pembrolizumab (Phase I patients only)

  -The RP2D of ramucirumab is defined as the highest dose level at which fewer than 2 patients of a cohort of three patients experience a dose-limiting toxicity (DLT) during the first cycle.

  Completion of first cycle of treatment for all patients enrolled in Phase I portion of study (estimated to be 2.5 months)

• Overall tumor response rate of ramucirumab and pembrolizumab (Phase II patients only)

  * Overall tumor response rate = number of participants with complete response + partial response * Complete response (CR)=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. * Partial response (PR)=At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  Through 28 days after completion of treatment (estimated to be 6 months)

Secondary Outcomes (6)

• Adverse event profile of the combination of ramucirumab and pembrolizumab (Phase I and II patients) as measured by the frequency of adverse events

  Through 28 days after completion of treatment (estimated to be 6 months)

• Duration of overall response (Phase II patients only)

  Through 28 days after completion of treatment (estimated to be 6 months)

• Progression-free survival (PFS) (Phase II patients only)

  Through 28 days after completion of treatment (estimated to be 6 months)

• Overall survival (OS) (Phase II patients only)

  Through 28 days after completion of treatment (estimated to be 6 months)

• Changes in quality of life as measured by FACT H&N (Phase II patients only)

  Baseline, start of cycle 2, and start of cycle 5 (estimated to be 12 weeks)

Study Arms (2)

Phase I: Ramucirumab + Pembrolizumab

EXPERIMENTAL

-Ramucirumab will be administered IV over 1 hour on Day 1 of each 21-day cycle. Pembrolizumab will be administered as per standard of care (IV at a dose of 200 mg over 30 minutes on Day 1 of each 21-day cycle). On Day 1, pembrolizumab will be given after ramucirumab.

Drug: Ramucirumab; Drug: Pembrolizumab; Procedure: Peripheral blood

Phase II: Ramucirumab + Pembrolizumab

EXPERIMENTAL

-Patients will be treated with ramucirumab at the RP2D on Day 1 and SOC pembrolizumab (200 mg IV over 30 minutes) on Day 1 of each 21-day cycle.

Drug: Ramucirumab; Drug: Pembrolizumab; Other: EORTC QLQ-30; Other: FACT H&N; Procedure: Peripheral blood

Interventions

Peripheral blood PROCEDURE

-Baseline

Phase I: Ramucirumab + Pembrolizumab; Phase II: Ramucirumab + Pembrolizumab

Ramucirumab DRUG

Ramucirumab is an investigational agent for this trial and will be supplied by Lilly Oncology, free of charge to the patient

Also known as: Cyramza

Phase I: Ramucirumab + Pembrolizumab; Phase II: Ramucirumab + Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab is commercially available

Also known as: Keytruda

Phase I: Ramucirumab + Pembrolizumab; Phase II: Ramucirumab + Pembrolizumab

EORTC QLQ-30 OTHER

-Screening, start of cycle 2, start of cycle 5

Phase II: Ramucirumab + Pembrolizumab

FACT H&N OTHER

-Screening, start of cycle 2, start of cycle 5

Phase II: Ramucirumab + Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Incurable HNSCC, defined as RM disease not amenable to cure by surgery and/or radiation therapy or patient with HNSCC declines or is ineligible for curative therapy
• In phase I, oral cavity, oropharynx, larynx, hypopharynx, nasopharynx, paranasal sinus, or salivary gland
• In phase II, oral cavity, oropharynx, larynx, or hypopharynx
• Disease Evaluation:
• In phase I, evaluable or measurable disease.
• In phase II, measurable disease per RECIST 1.1
• Prior Treatment:
• For phase I, any number of lines of prior therapy for RM-HNSCC.
• For phase II, no prior systemic therapy for RM-HNSCC.
• At least 18 years of age.
• Performance status 0-2 (ECOG).
• Adequate blood and organ function as defined:
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Hemoglobin ≥ 9.0 g/dL

You may not qualify if:

• Phase II: prior PD-1 inhibitor for treatment of incurable HNSCC. For phase I, prior PD-1 inhibitor therapy in the incurable setting is permitted.
• Radiation, chemotherapy, targeted or investigational therapy within 14 days of treatment start.
• Major surgery, presence of a non-healing, non-malignant ulcer within 14 days of treatment start; History of significant tumor site bleeding within 14 days of study consent.
• History of other malignancy ≤ 1 year previous with the exception of completely resected skin carcinoma or other cancers with a low risk of recurrence.
• 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).
• Receiving any other investigational agents.
• Ongoing toxicity attributed to prior anti-cancer therapy that is \> grade 1, except alopecia, anemia, fatigue or rash.
• Active central nervous system metastases: defined as currently receiving radiation therapy to metastatic CNS disease. Once radiation therapy is completed, patients with CNS disease are eligible if they meet all other criteria for enrollment.
• History of severe allergic reactions attributed to agents used in the study.
• Serious uncontrolled inter-current illness within the 3 months prior to study entry or psychiatric illness/social situations that would limit compliance with study requirements.
• Receiving systemic steroid therapy (in dosing exceeding 20 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab.
• Has an active autoimmune disease (i.e. rheumatoid arthritis, lupus, Sjogren's syndrome) that has required IV or subcutaneous systemic treatment in the past 6 months (excluding rituxin). Replacement therapy (i.e. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of system treatment.
• GI perforation or fistula within 6 months of first dose of protocol therapy
• History of GI issues such as inflammatory bowel disease, ulcerative colitis, or Crohn's disease.
• Poorly controlled hypertension (defined as high blood pressure measurements \[systolic blood pressures of ≥ 160 mmHg or diastolic blood pressures of \> 100 mmHg\] documented during the two-week interval prior to enrollment). Initiation or adjustment of antihypertensive medications to control blood pressure is permitted prior to study entry.

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 Publications (1)

• Adkins D, Ley JC, Liu J, Oppelt P. Ramucirumab in combination with pembrolizumab for recurrent or metastatic head and neck squamous cell carcinoma: a single-centre, phase 1/2 trial. Lancet Oncol. 2024 Jul;25(7):888-900. doi: 10.1016/S1470-2045(24)00204-3. Epub 2024 Jun 5.

  PMID: 38851207 DERIVED

Related Links

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

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Ramucirumab; pembrolizumab

Condition Hierarchy (Ancestors)

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

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 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2018
• First Posted: August 29, 2018
• Study Start: May 29, 2019
• Primary Completion: April 30, 2026
• Study Completion: April 30, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)