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

Study on Treatments for Head and Neck Cancer

G
Greg Durm, MD

Primary Investigator

Recruiting
18 years - 100 years
All
Phase 2
2 participants needed
2 Locations

Brief description of study

The purpose of this research study is to evaluate the effectiveness of using a combination of pembrolizumab and olaparib when given before and after standard chemoradiation therapy in treating locally advanced head and neck squamous cell carcinoma. Pembrolizumab and olaparib are drugs that are approved for head and neck cancer treatment. However, FDA has not approved the use of these two drugs together in treating head and neck cancer.
 
Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office 
Phone: (317) 278-5632

Detailed description of study

Treatment outcomes are poor for patients with locally advance human papilloma virus (HPV) negative and high-risk HPV positive head and neck squamous cell carcinoma (HNSCC). One standard of care (SOC) for HNSCC is definitive chemoradiotherapy (CRT). This study will evaluate the safety and efficacy of the addition of pembrolizumab, an anti-programmed death-1 (PD1) inhibitor, and olaparib, a Polyadenosine 5'diphosphoribose polymerization (PARP) inhibitor, before and after SOC CRT, which will be delivered in 70 Gray in 35 fractions with concurrent weekly cisplatin 40 mg/m2 over 7 weeks.

Treatment will be offered in three sequential phases. In the induction phase, participants will receive one infusion of pembrolizumab and will take olaparib tablets for a total of 21 days. In the chemoradiation phase, radiation therapy will administered daily (excluding weekends) and cisplatin infusion will be given weekly. In the maintenance phase, pembrolizumab infusion will be done once every 6 weeks in additional to twice daily olaparib tablets for up to 8 treatment cycles that are 42-days per cycle.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Squamous Cell Carcinoma of Head and Neck, Cancer
  • Age: 18 years - 100 years
  • Gender: All

Inclusion Criteria:

  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

This study investigates the use of investigational medications in treating locally advanced head and neck squamous cell carcinoma. The purpose of this study is to see how effective a combination of two investigational medications, given before and after standard treatment, is in treating this type of cancer. Head and neck squamous cell carcinoma is a type of cancer that affects the cells lining the mouth, nose, and throat.

In the study, participants will go through three phases of treatment. First, they will receive an infusion of the investigational medication and take tablets of another investigational medication for 21 days. Then, they will undergo radiation therapy and receive a weekly infusion of a different medicine. Lastly, they will continue with the investigational medication infusion every six weeks and take tablets twice a day for up to eight cycles, each lasting 42 days.

  • Who can participate: Adults over 18 years old with certain types of head and neck cancer can join. Participants must have a biopsy-confirmed diagnosis and meet specific health criteria, including no prior treatment attempts for this cancer.
  • Study details: Participants will receive investigational medications through infusions and tablets at various stages of the study. They will also undergo standard radiation therapy and receive another medication weekly. Participants must have measurable lesions. A placebo is not used in this study.
Updated on 23 Sep 2025. Study ID: CTO-LCCC2047

Find a site

We have submitted the contact information you provided to the research team at {{SITE_NAME}}. A copy of the message has been sent to your email for your records.
Would you like to be notified about other trials? Sign up for Patient Notification Services.
Sign up

Send a message

Enter your contact details to connect with study team

Investigator Avatar

Primary Contact

First name*
Last name*
Email*
Phone number*
Other language

Interested in the study?

Select a study center that’s convenient for you, and get in touch with the study team.

Connect with the Study Team