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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating head and neck cancer by combining two drugs, pembrolizumab (an immunotherapy) and olaparib (a PARP inhibitor), with standard chemoradiation therapy. The researchers aim to determine if using these drugs together before and after the usual treatment enhances its effectiveness. This study targets individuals with advanced head and neck squamous cell carcinoma, particularly those who have not undergone surgery or other treatments for this cancer. Participants must have a specific cancer stage confirmed by a biopsy and a history of significant tobacco use. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking advancements in cancer therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that using pembrolizumab and olaparib together is generally safe for patients. Studies have found that these drugs can be safely combined to treat certain advanced cancers. Patients' conditions did not worsen for about eight months, indicating the treatment was well-tolerated during that time.

Both pembrolizumab and olaparib have FDA approval for treating head and neck cancer, but their combined use for this condition is new and still under investigation. While some safety information exists from their individual use, researchers are still learning about their combined effects.

Earlier studies revealed that patients with specific gene mutations responded well to the combination, and no major safety issues were reported. This suggests the treatment is generally well-tolerated, though individual experiences may differ. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for head and neck cancer, which typically involve chemotherapy and radiation, the combination of pembrolizumab and olaparib offers a novel approach by enhancing the body’s immune response and targeting cancer cells' DNA repair mechanisms. Pembrolizumab is an immunotherapy drug that helps the immune system detect and attack cancer cells more effectively. Meanwhile, olaparib is a PARP inhibitor that prevents cancer cells from repairing their DNA, leading to their death. Researchers are excited about this combination because it holds the potential to improve outcomes by not only attacking the cancer cells directly but also boosting the body's natural defenses against the disease.

What evidence suggests that the combination of pembrolizumab and olaparib could be effective for head and neck cancer?

Research shows that combining pembrolizumab and olaparib may help treat certain cancers. One study found that patients using this combination lived about 8 months without cancer progression and had a total survival time of just over 2 years. This combination proved especially effective in tumors with specific gene changes. While pembrolizumab alone has benefited head and neck cancer patients, researchers continue to study whether adding olaparib can enhance its effectiveness. In this trial, participants will receive both pembrolizumab and olaparib alongside standard treatments to determine if this combination can improve head and neck cancer treatment by enhancing the effects of standard therapies. ^{1 2 4 6 7}

Who Is on the Research Team?

Siddharth Sheth, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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 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]

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 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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/OA-25-00049

Olaparib, Pembrolizumab, and Carboplatin as First-Line ... Patients lived without disease progression for about 8 months and overall lived for just over 2 years. These results suggest that adding ...

2. onclive.com onclive.com/view/olaparib-plus-pembrolizumab-shows-efficacy-in-hrr-gene-mutated-advanced-tumors-with-without-hrd-positivity

Olaparib Plus Pembrolizumab Shows Efficacy in HRR ... Olaparib plus pembrolizumab was safe and effective in HRR gene–mutated and/or HRD-positive advanced tumors.

3. merck.com merck.com/news/merck-provides-update-on-phase-3-keylynk-006-trial-evaluating-keytruda-pembrolizumab-plus-maintenance-lynparza-olaparib-for-certain-patients-with-metastatic-nonsquamous-non-small-cell/

Merck Provides Update on Phase 3 KEYLYNK-006 Trial ... The safety profiles of KEYTRUDA and LYNPARZA in this trial were consistent with those observed in previously reported studies for the individual ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11694497/

Real-World Evidence on the Effectiveness of Pembrolizumab ... The study showed some beneficial effects of pembrolizumab monotherapy in recurrent/metastatic/unresectable HNSCC patients in real-world scenarios.

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCT05366166

Pembrolizumab in Combination with Olaparib before and ... This phase II trial tests whether pembrolizumab in combination with olaparib given before and after standard chemoradiation works to control cancer in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05366166

NCT05366166 | Pembrolizumab Plus Olaparib in LA-HNSCC Treatment outcomes are poor for patients with locally advance human papilloma virus (HPV) negative and high-risk HPV positive head and neck squamous cell ...

7. merck.com merck.com/news/merck-announces-keylynk-008-trial-evaluating-keytruda-pembrolizumab-plus-lynparza-olaparib-for-patients-with-metastatic-squamous-non-small-cell-lung-cancer-to-stop-for-futility/

Merck Announces KEYLYNK-008 Trial Evaluating ... KEYLYNK-008 is a randomized, triple-blind, Phase 3 trial (ClinicalTrials.gov, NCT03976362) evaluating KEYTRUDA in combination with chemotherapy ...