Pembrolizumab + Olaparib for Head and Neck Cancer

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Siddharth Sheth, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: Glucocorticoids

Disqualifiers: Prior HNSCC, Severe comorbidity, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are taking systemic glucocorticoids (a type of steroid medication), you may need to stop unless they are used for specific symptoms related to the study.

What data supports the effectiveness of the drugs pembrolizumab and olaparib for head and neck cancer?

Research shows that pembrolizumab, an immune checkpoint inhibitor, has demonstrated antitumor activity in recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) and is approved for use in these cases. Additionally, combining pembrolizumab with chemoradiotherapy has been shown to be safe and feasible for locally advanced HNSCC, suggesting potential effectiveness in this context. ^{1 2 3 4 5}

Is the combination of pembrolizumab and olaparib safe for head and neck cancer treatment?

Pembrolizumab has been studied in combination with other treatments for head and neck cancer and is generally considered safe, though it can cause side effects like anemia (low red blood cell count), stomatitis (mouth sores), and neutropenia (low white blood cell count). No treatment-related deaths were reported in the studies reviewed. ^{1 2 5 6 7}

What makes the treatment with Pembrolizumab and Olaparib unique for head and neck cancer?

This treatment combines pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with olaparib, a drug that targets cancer cell DNA repair mechanisms. This combination is novel for head and neck cancer as it integrates immunotherapy with a targeted therapy, potentially enhancing the effectiveness of standard treatments like radiation and chemotherapy. ^{1 2 3 5 8}

Eligibility Criteria

This trial is for adults over 18 with certain types of head and neck squamous cell carcinoma (HNSCC) that haven't been treated yet. Participants need to be in good physical condition, able to follow the study plan, and have a tumor assessable by imaging. They can't join if they've had other cancer treatments recently, can't swallow pills, are ineligible for cisplatin therapy, or have severe medical issues.

Inclusion Criteria

I have advanced stage mouth or throat cancer, not caused by HPV unless I have a heavy smoking history.

I am fully active or can carry out light work.

I have at least one cancer lesion that can be monitored through scans.

Exclusion Criteria

I cannot swallow pills before starting the study treatment.

I am taking steroids only for immune-related symptoms, not for other reasons.

I have had cancer before, but it won't affect this study's treatment, except for head and neck cancer treated within the last 3 years.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive one infusion of pembrolizumab and take olaparib tablets for 21 days

3 weeks

Chemoradiation

Radiation therapy administered daily with weekly cisplatin infusion over 7 weeks

7 weeks

Maintenance

Pembrolizumab infusion every 6 weeks and olaparib tablets twice daily for up to 8 cycles

Up to 48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• Cisplatin (Chemotherapy)
• External Beam Radiotherapy (Radiation)
• IMRT (intensity modulated radiation therapy) (Radiation)
• Olaparib (PARP Inhibitor)
• Pembrolizumab (PD-1 Inhibitor)

Trial Overview The trial tests pembrolizumab plus olaparib before and after standard chemoradiation therapy for advanced HNSCC. These drugs are approved separately but not together; this study examines their combined effectiveness when paired with chemo and radiation.

Participant Groups

Group I: Single Arm Experimental Treatment 4 Interventions

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

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺 Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

🇺🇸 Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

🇨🇦 Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

🇯🇵 Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

UNC Lineberger Chapel Hill, NC

University of Louisville, Brown Cancer Center Louisville, KY

Medical University of South Carolina (MUSC) Charleston, SC

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center Lead Sponsor

Merck Sharp & Dohme LLC Industry Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. [2023] Although cisplatin plus radiotherapy is a standard treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC), cisplatin contraindication is common. Radiation elicits and promotes tumor-directed immune stimulation, which may potentiate anti-PD-1 therapy. We provide the first efficacy report of combined pembrolizumab and definitive radiotherapy in LA-HNSCC.

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019] Until recently, palliative options for the treatment of platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have been cytotoxic chemotherapy and EGFR inhibitors. These agents offer limited efficacy with substantial toxicity. The development of novel immune checkpoint inhibitors has challenged the standard treatment. Pembrolizumab is a potent and highly selective humanized monoclonal antibody that blocks the interaction between PD-1, an immune checkpoint receptor and its ligands PD-L1 and -2. In August 2016, the US FDA approved the use of pembrolizumab in R/M HNSCC following disease progression on or after platinum-containing chemotherapy. This review highlights the pharmacology, therapeutic efficacy and tolerability data relevant to the use of pembrolizumab for the treatment of R/M HNSCC. Readers will gain greater insight into the HNSCC tumor microenvironment, available biomarkers, and learn about important clinical considerations associated with the use of pembrolizumab and similar immune checkpoint inhibitors.

3. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. [2022] Pembrolizumab is a humanized monoclonal antibody that blocks interaction between programmed death receptor-1 (PD-1) and its ligands (PD-L1, PD-L2). Although pembrolizumab is approved for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), its role in the management of locally advanced (LA) disease is not defined. We report a phase IB study evaluating the safety and efficacy of adding pembrolizumab to cisplatin-based chemoradiotherapy in patients with LA HNSCC.

4. Greece pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. [2023] This study evaluated the efficacy of nivolumab and pembrolizumab in treating platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas (R/M-HNSCC).

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. [2021] Current treatment guidelines for patients with locally advanced head and neck squamous cell carcinoma (HNSCC) recommend multimodal treatment, including chemoradiation therapy (CRT) or surgery followed by radiation, with or without chemotherapy. The immune checkpoint inhibitor pembrolizumab has previously demonstrated antitumor activity in recurrent and/or metastatic HNSCC in large Phase III trials. For patients with locally advanced disease, Phase Ib data on the use of pembrolizumab in combination with chemoradiation have shown the approach to be safe and feasible. We describe here the design and rationale for KEYNOTE-412, a randomized, double-blind, Phase III trial investigating pembrolizumab or placebo administered concurrently with CRT and as maintenance treatment in patients with locally advanced HNSCC. Clinical Trial Registration: NCT03040999 (ClinicalTrials.gov).

6. China pubmed.ncbi.nlm.nih.gov

A pilot study of camrelizumab with docetaxel and cisplatin for the first line treatment in recurrent/metastatic oral squamous cell carcinoma. [2023] Pembrolizumab with cisplatin and 5-fluorouracil showed survival benefit but relatively high occurrence of treatment-related adverse events (TRAEs) for recurrent/metastatic oral squamous cell carcinoma (R/M OSCC). A more tolerable regime is needed. This trial enrolled 20 R/M OSCC patients with previously untreated and PD-L1 positive. Patients were administered camrelizumab with docetaxel and cisplatin every 3 weeks for six cycles, followed by camrelizumab monotherapy every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was occurrence of grade ≥ 3 TRAEs, secondary endpoints included overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). 45% patients experienced grade ≥ 3 TRAEs, which the most common were anemia (15%), stomatitis (15%), and neutropenia (10%). The most common potential immune-related adverse events were reactive cutaneous capillary endothelial proliferation (RCCEP; 60%), hypothyroidism (35%), and pneumonitis (15%). No treatment-related deaths occurred. The median OS, PFS, and ORR was 14.4 months, 5.35 months, and 40.0% respectively. The study also found RCCEP occurrence, lower FOXP3+ cells, and higher density of intratumor tertiary lymphoid structure were associated with improved efficacy. Our data suggest that camrelizumab with docetaxel/cisplatin as first-line therapy was well tolerable and had potentially favorite efficacy in PD-L1-positive patients with R/M OSCC.

7. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab with preoperative neoadjuvant chemotherapy in patients with resectable locally advanced head and neck squamous cell carcinomas. [2023] This study aimed to explore the efficacy and safety of pembrolizumab combined with chemotherapy as neoadjuvant therapy in patients with resectable locally advanced head and neck squamous cell carcinomas (LA-HNSCCs).

8. Switzerland pubmed.ncbi.nlm.nih.gov

Depth of response may predict clinical outcome in patients with recurrent/metastatic head and neck cancer treated with pembrolizumab-containing regimens. [2023] Pembrolizumab-containing regimens are standards of care for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). The depth of response (DpR) predicts the survival of patients with several types of solid cancers; however, its association with the survival outcomes of patients with R/M HNSCC treated with pembrolizumab-containing regimens remains unclear.