Pembrolizumab + Olaparib for Head and Neck Cancer

Recruiting at 3 trial locations

Overseen By Stephanie Corbett

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: Glucocorticoids

Disqualifiers: Prior HNSCC, Severe comorbidity, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

45 Participants Needed

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}

Research Team

Siddharth Sheth, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

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.

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
• External Beam Radiotherapy
• IMRT (intensity modulated radiation therapy)
• Olaparib
• Pembrolizumab

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

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In a phase II study involving 29 patients with locally advanced head and neck squamous cell carcinoma who were ineligible for cisplatin, the combination of pembrolizumab and radiotherapy showed promising efficacy, with a 24-month progression-free survival rate of 71%.

The treatment was generally well-tolerated, although a significant number of patients experienced grade 3/4 lymphopenia (58.6%), indicating the need for monitoring immune cell changes during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. Weiss, J., Sheth, S., Deal, AM., et al.[2023]

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the FDA for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), offering a new option with potentially improved efficacy compared to traditional chemotherapy and EGFR inhibitors.

This review discusses the pharmacology and tolerability of pembrolizumab, emphasizing its mechanism of action by blocking the PD-1 receptor, which may enhance the immune response against HNSCC tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. Sheth, S., Weiss, J.[2019]

In a phase IB study involving 59 patients with locally advanced head and neck squamous cell carcinoma, the combination of pembrolizumab with cisplatin-based chemoradiotherapy was found to be safe, with a high completion rate of treatment and only 8.8% of patients experiencing immune-related adverse events.

The treatment showed promising efficacy, with complete response rates of 85.3% for HPV-positive and 78.3% for HPV-negative patients, suggesting that this combination warrants further investigation.

NCBI (Pubmed)

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. Powell, SF., Gold, KA., Gitau, MM., et al.[2022]

In a study of platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas involving 36 patients, both nivolumab and pembrolizumab showed effectiveness, with median overall survival of 16.9 months for nivolumab and 19.2 months for pembrolizumab, indicating similar efficacy between the two treatments.

The median progression-free survival was 4.8 months for nivolumab and 9.3 months for pembrolizumab, with objective response rates of 38% and 47%, respectively, suggesting that both drugs are viable options for treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Yamashita, G., Okamoto, I., Ito, T., et al.[2023]

The Phase III trial KEYNOTE-412 is designed to evaluate the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, when used alongside chemoradiation therapy (CRT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Previous Phase Ib studies have indicated that combining pembrolizumab with CRT is safe and feasible, supporting its potential use in this larger trial to improve treatment outcomes for patients with locally advanced HNSCC.

NCBI (Pubmed)

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. Machiels, JP., Tao, Y., Burtness, B., et al.[2021]

In a trial involving 20 patients with recurrent/metastatic oral squamous cell carcinoma, the combination of camrelizumab with docetaxel and cisplatin showed a median overall survival of 14.4 months and an overall response rate of 40%, indicating promising efficacy.

The treatment was generally well tolerated, with 45% of patients experiencing grade ≥ 3 treatment-related adverse events, the most common being anemia and stomatitis, but no treatment-related deaths occurred.

NCBI (Pubmed)

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. Ju, H., Wei, D., Wu, Y., et al.[2023]

In a study of 22 patients with resectable locally advanced head and neck squamous cell carcinomas, the combination of pembrolizumab and chemotherapy resulted in a postoperative pathological complete response (pCR) rate of 36.4%, indicating significant efficacy as a neoadjuvant treatment.

The treatment did not adversely affect surgical safety, with a high rate of laryngeal function preservation at 90.9%, and no delays to surgery due to adverse drug reactions, although delayed wound healing was noted in 22.7% of patients.

NCBI (Pubmed)

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. Wang, K., Gui, L., Lu, H., et al.[2023]

In a study of 66 patients with recurrent and metastatic head and neck squamous cell carcinoma treated with pembrolizumab, the one-year overall survival rate was 69.4%, indicating the regimen's effectiveness as a first-line therapy.

The depth of response (DpR) was found to be a significant predictor of survival outcomes, with a greater tumor reduction (≥-45%) correlating with improved overall survival and progression-free survival rates.

NCBI (Pubmed)

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. Saijo, K., Imai, H., Ouchi, K., et al.[2023]

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]

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

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019]

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]

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]

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]

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]

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]

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]