Combining pembrolizumab and olaparib for advanced head and neck cancer treatment

A Phase II Trial of Induction and Maintenance Pembrolizumab and Olaparib in Locally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)

Phase 2 Interventional UNC Lineberger Comprehensive Cancer Center · NCT05366166

This study is testing if combining two drugs, pembrolizumab and olaparib, can help people with advanced head and neck cancer do better after standard treatment.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment45 (estimated)
Ages18 Years and up
SexAll
SponsorUNC Lineberger Comprehensive Cancer Center Academic / other
Drugs / interventionsradiation, pembrolizumab
Locations4 sites (Indianapolis, Indiana and 3 other locations)
Trial IDNCT05366166 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of pembrolizumab and olaparib in treating locally advanced head and neck squamous cell carcinoma (HNSCC) before and after standard chemoradiation therapy. Participants will undergo a three-phase treatment regimen, starting with pembrolizumab infusion and olaparib tablets, followed by chemoradiation with cisplatin, and concluding with maintenance therapy involving both drugs. The study aims to improve treatment outcomes for patients with HPV-negative and high-risk HPV-positive HNSCC, which currently have poor prognoses.

Who should consider this trial

Good fit: Ideal candidates include adults over 18 with biopsy-confirmed advanced stage head and neck squamous cell carcinoma, particularly those with HPV-negative tumors or specific HPV-associated cases.

Not a fit: Patients with early-stage head and neck cancer or those who do not meet the specific eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this combination therapy could significantly improve treatment outcomes for patients with advanced head and neck cancer.

How similar studies have performed: While the combination of pembrolizumab and olaparib has not been previously tested together in this context, both drugs have shown promise in treating head and neck cancer individually.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

In order to participate in this study, a subject must meet all of the eligibility criteria outlined below.

1. Age \>18 years on the day of signing the consent
2. Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
3. Subject is willing and able to comply with study procedures based on the judgment of the investigator or protocol designee. The subject must be willing to consent to a mandatory pre-study biopsy unless sufficient archival tissue is available.
4. Biopsy confirmed American Joint Committee on Cancer 8th Edition35 stage III-IV B oral cavity squamous cell carcinoma (SCC), p16-negative oropharyngeal SCC, stage III-IVB hypopharyngeal SCC, stage III-IVB laryngeal SCC -OR- HPV-associated oropharyngeal SCC (p16 positive or HPV-associated) T4 or N3 , T1-3 N2 or T3N0-1 with \>10 pack-year tobacco history
5. At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by imaging (CT/ PET) and is suitable for repeated assessment.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
7. No prior curative attempts for this cancer (i.e., surgery, radiation, systemic therapy) and not currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of the study intervention. No evidence of metastatic disease (M0)

Exclusion Criteria

1. Subjects with prior and concurrent malignancies of different tumor types whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the study drug are eligible with the following exception: Subjects with prior history of HNSCC treated \< 3 years to the date of consent.
2. Cisplatin-ineligible as defined in the protocol.
3. Severe, active medical comorbidity. Subjects are considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography scan or any psychiatric disorder that prohibits obtaining informed consent.
4. Subjects unable to swallow orally administered medication prior to initiation of study treatment.
5. Systemic glucocorticoids for any purpose other than to modulate symptoms from an event of clinical interest of suspected immunologic etiology

Where this trial is running

Indianapolis, Indiana and 3 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Squamous Cell Carcinoma of Head and Neckhead and necksquamous cell carcinomaHPV negativepembrolizumabolaparibPARP inhibitoranti-PD1 inhibitor
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.