Pembrolizumab Plus Olaparib in LA-HNSCC

UNC Lineberger Comprehensive Cancer Center

Status and phase: Active, not recruiting; Phase 2

Conditions: Squamous Cell Carcinoma of Head and Neck

Treatments: Biological: Pembrolizumab; Drug: Cisplatin; Drug: Olaparib; Radiation: IMRT (intensity modulated radiation therapy)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05366166

LCCC2047

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 45 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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45 participants in 1 patient group

Single Arm

Experimental group

Description:

The participants will receive neoadjuvant and adjuvant pembrolizumab and olaparib combination plus standard of care (chemoradiation therapy) as defined in the protocol.

Treatment:

Radiation: IMRT (intensity modulated radiation therapy)

Drug: Olaparib

Drug: Cisplatin

Biological: Pembrolizumab