Olaparib in Combination With Pembrolizumab and Carboplatin as First-Line Treatment of Recurrent or Metastatic Head and Neck Squamous-Cell Carcinoma

NCT04643379 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 202104144
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, patients with recurrent or metastatic head and neck squamous cell carcinoma will receive first line treatment with olaparib, pembrolizumab, and carboplatin. The primary hypothesis is that olaparib, pembrolizumab and carboplatin will result in an overall response rate (ORR) higher than the historical ORR observed with pembrolizumab, platinum and 5-FU.

Conditions

Recurrent Head and Neck Squamous Cell Carcinoma; Metastatic Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) as assessed by iRECIST

  Through completion of treatment (estimated to be 2 years)

Secondary Outcomes (7)

• Duration of response (DOR)

  Through completion of treatment (estimated to be 2 years)

• Progression-free survival (PFS)

  Through completion of follow-up (estimated to be 3 years)

• Incidence of adverse events

  Through 28 day follow-up (estimated to be 25 months)

• Overall survival (OS)

  Through completion of follow-up (estimated to be 3 years)

• HR and PTEN gene status

  Through completion of follow-up (estimated to be 3 years)

Study Arms (1)

Olaparib + Pembrolizumab + Carboplatin AUC

EXPERIMENTAL

-Patients enrolled in this study will receive olaparib, pembrolizumab and carboplatin in three-week cycles for six cycles, followed by maintenance therapy with three-week cycles of olaparib and pembrolizumab. Treatment will continue until disease progression, intolerable toxicity, patient or physician decision to stop therapy, or after 35 cycles, whichever occurs first. Drug dosing for each cycle is as follows: * Olaparib 200 mg twice per day (bid) by mouth (po) Days 1-10 for the first six cycles (when given with carboplatin), followed by 400 mg bid po Days 1-21 of subsequent cycles. * Pembrolizumab 200 mg intravenous (IV) Day 1. * Carboplatin AUC 5 IV on Day 1 for up to six cycles.

Drug: Olaparib; Drug: Pembrolizumab; Drug: Carboplatin; Procedure: Peripheral blood draw

Interventions

Olaparib DRUG

Supplied by Merck \& Co.

Also known as: Lynparza

Olaparib + Pembrolizumab + Carboplatin AUC

Pembrolizumab DRUG

Supplied by Merck \& Co.

Also known as: Keytruda

Olaparib + Pembrolizumab + Carboplatin AUC

Carboplatin DRUG

Commercially available

Olaparib + Pembrolizumab + Carboplatin AUC

Peripheral blood draw PROCEDURE

Baseline (cycle 1 day 1), cycle 2 day 1, and at disease progression

Olaparib + Pembrolizumab + Carboplatin AUC

Eligibility Criteria

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

You may qualify if:

• Diagnosis of histologically or cytologically confirmed recurrent or metastatic HNSCC of the oral cavity, oropharynx, larynx, hypopharynx, or p16+ SCC of the neck (unknown primary).
• Measurable disease per RECIST. Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
• Incurable disease, or ineligible for (including patient declined) local therapy.
• At least 18 years of age.
• ECOG performance status ≤ 1
• Life expectancy ≥ 16 weeks.
• Normal bone marrow and organ function as defined below (specimens must be collected within 10 days prior to the start of study treatment):
• Hemoglobin ≥ 10.0 g/dL (criteria must be met without erythropoietin dependency and without packed red blood cell transfusion within the last 2 weeks)
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• INR or PT ≤ 1.5 x institutional upper limit of normal (IULN) and aPTT ≤ 1.5 x IULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
• Total bilirubin ≤ 1.5 x IULN
• AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN unless liver metastases are present (in which case they must be ≤ 5 x IULN)
• Serum creatinine \<1.5 x ULN or creatinine clearance ≥ 51 mL/min by Cockcroft-Gault or based on a 24-hour urine test
• Known p16 expression, if oropharyngeal primary.

You may not qualify if:

• Progression within 6 months of curatively intended systemic therapy given for locoregionally advanced disease.
• Investigational therapy within 28 days of treatment start.
• Prior systemic therapy for recurrent or metastatic disease.
• Known CNS metastases/leptomeningeal metastatic disease.
• Other malignancy unless curatively treated with no evidence of disease for ≥ 2 years except: adequately treated non-melanoma skin cancer, curative treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), stage 1 grade 1 endometrial carcinoma; or low risk-disease per discretion of the PI.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib, pembrolizumab, carboplatin, or other agents used in the study.
• Has received prior therapy with an anti-PD-1, andti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137).
• Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
• Concomitant use of known strong CYP3A inducers (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine, and St. John's wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
• Resting ECG indicating uncontrolled, potentially reversible cardiac conditions as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation \> 500 ms, electrolyte disturbances, etc.) or patients with congenital long QT syndrome.
• Diagnosis of myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
• Major surgery within 2 weeks of starting study treatment; must have recovered from any effects of major surgery.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic corticosteroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of treatment.
• Received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of pembrolizumab. Administration of killed vaccines is allowed. Examples of live vaccines is allowed. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist®) are live attenuated vaccines and are not allowed.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Merck Sharp & Dohme LLC: collaborator
• Joseph Sanchez Foundation: 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

Squamous Cell Carcinoma of Head and Neck

Interventions

olaparib; pembrolizumab; Carboplatin

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)

Coordination Complexes; Organic Chemicals

Study Officials

• Douglas Adkins, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 18, 2020
• First Posted: November 25, 2020
• Study Start: August 7, 2021
• Primary Completion: October 16, 2025
• Study Completion (Estimated): October 31, 2028
• Last Updated: October 22, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)