Olaparib + Pembrolizumab + Carboplatin for Head and Neck Cancer

Not currently recruiting at 1 trial location

Overseen By Douglas R. Adkins

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: CNS metastases, Autoimmune disease, 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: 3

Duration: Up to 105 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs—olaparib, pembrolizumab, and carboplatin—to treat head and neck cancer that has returned or spread. The goal is to determine if this combination outperforms previous treatments. Individuals with recurring or spreading head and neck squamous cell carcinoma who cannot be cured or have opted out of local therapy might be suitable for this trial. Participants will receive these drugs in cycles and continue as long as the treatment remains effective and tolerable. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires a washout period for certain medications. If you are taking strong or moderate CYP3A inhibitors or inducers, you will need to stop them 2 to 5 weeks before starting the trial, depending on the specific medication. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Research has shown that using olaparib, pembrolizumab, and carboplatin together may be promising for treating certain cancers. One study found that this combination helped patients live longer without the disease worsening, for about 8 months, and increased overall survival to just over 2 years. These results suggest the treatment is quite effective.

Regarding safety, pembrolizumab alone has been linked to serious side effects like pneumonia and thyroid problems. However, its overall safety is considered acceptable. While there is less specific information on the combination with olaparib and carboplatin, the study's phase indicates that the treatment has undergone enough testing to be considered relatively safe for further research. Participants in these trials receive close monitoring to manage any side effects that may occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of olaparib, pembrolizumab, and carboplatin for head and neck cancer because it brings together a unique blend of mechanisms. Unlike standard treatments that often focus solely on chemotherapy, this combo includes olaparib, a PARP inhibitor that targets cancer cells' ability to repair their DNA, potentially making them more vulnerable to treatment. Pembrolizumab, an immune checkpoint inhibitor, helps the immune system recognize and attack cancer cells more effectively. This multi-pronged approach not only targets the cancer directly but also enhances the body's immune response, offering hope for improved outcomes compared to existing therapies.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research has shown that combining the drugs olaparib, pembrolizumab, and carboplatin may help treat head and neck cancer. In earlier studies, patients who received this combination as their first treatment lived without their cancer worsening for about 8 months and lived overall for just over 2 years. This combination showed a better response rate compared to traditional treatments. In this trial, participants will receive this combination therapy, which includes pembrolizumab, a drug particularly effective in treating challenging cases of head and neck cancer. These results suggest that this combination might outperform some current treatments for this type of cancer. ^{1 2 4 5 6}

Who Is on the Research Team?

Douglas R. Adkins

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

Adults with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who haven't had certain prior treatments, have measurable disease, good organ function, no serious allergies to study drugs, can swallow pills, and are not pregnant. Men must use contraception.

Inclusion Criteria

Life expectancy ≥ 16 weeks

AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN unless liver metastases are present (in which case they must be ≤ 5 x IULN)

My kidney function, measured by creatinine levels or clearance, is within the required range.

Exclusion Criteria

I am not planning to become pregnant or father a child during the study and for 120 days after.

Pregnant and/or breastfeeding. A WOCBP who has a positive urine pregnancy test within 72 hours of first dose of treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

I haven't needed strong medication for an autoimmune disease in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olaparib, pembrolizumab, and carboplatin in three-week cycles for six cycles, followed by maintenance therapy with olaparib and pembrolizumab until disease progression or up to 35 cycles.

Up to 105 weeks

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Estimated 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Olaparib
• Pembrolizumab

Trial Overview The trial tests a combination of Olaparib with Pembrolizumab and Carboplatin as the first line of treatment for HNSCC. It aims to see if this combo improves response rates compared to historical data from similar treatments.

How Is the Trial Designed?

Group I: Olaparib + Pembrolizumab + Carboplatin AUC Experimental Treatment 4 Interventions

-Patients enrolled in this study will receive olaparib, pembrolizumab and carboplatin in three-week cycles for six cycles, followed by maintenance therapy with three-week cycles of olaparib and pembrolizumab. Treatment will continue until disease progression, intolerable toxicity, patient or physician decision to stop therapy, or after 35 cycles, whichever occurs first. Drug dosing for each cycle is as follows: * Olaparib 200 mg twice per day (bid) by mouth (po) Days 1-10 for the first six cycles (when given with carboplatin), followed by 400 mg bid po Days 1-21 of subsequent cycles. * Pembrolizumab 200 mg intravenous (IV) Day 1. * Carboplatin AUC 5 IV on Day 1 for up to six cycles.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

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

Joseph Sanchez Foundation

Collaborator

Trials

1

Recruited

30+

Published Research Related to This Trial

In a study with 882 patients over a median follow-up of 45 months, pembrolizumab and pembrolizumab-chemotherapy showed significant improvements in overall survival compared to cetuximab-chemotherapy for recurrent/metastatic head and neck squamous cell carcinoma, particularly in patients with high PD-L1 expression (CPS ≥ 20).

The analysis also indicated that patients who received pembrolizumab-based therapies had favorable outcomes in subsequent treatments, with improved progression-free survival on next-line therapies, highlighting the long-term efficacy of pembrolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. Harrington, KJ., Burtness, B., Greil, R., et al.[2023]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

In a study of 167 patients with recurrent/metastatic squamous cell carcinoma of the head and neck treated with pembrolizumab, the median overall survival was 22.7 months and progression-free survival was 5.1 months for those receiving pembrolizumab alone, indicating significant efficacy.

The presence of immune-related adverse events (irAEs) was associated with better progression-free survival, suggesting that these side effects may serve as important prognostic factors in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study. Okada, T., Fushimi, C., Matsuki, T., et al.[2023]

In a study of 38 patients with p16+ oropharyngeal squamous cell carcinoma, there was a 76% agreement in PD-L1 combined positive scores (CPS) between primary tumors and lymph node metastases, indicating variability in scoring between these specimens.

The interobserver agreement for CPS scoring was fair to substantial, suggesting that additional evaluations may be necessary to ensure accurate scoring, especially for patients who might benefit from immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. Kaur, A., Kuchta, K., Watkin, W., et al.[2023]

In a small retrospective study of 10 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, the combination of pembrolizumab with carboplatin and paclitaxel (pembro + CP) was well tolerated, with 100% of patients experiencing mild adverse events and 30% experiencing more severe side effects.

The overall response rate (ORR) was 14% with one complete response, and the disease control rate (DCR) was 43%, indicating that while the treatment showed some effectiveness, further prospective studies are needed to fully evaluate its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer. Cabezas-Camarero, S., Merino-Menéndez, S., Cabrera-Martín, MN., 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]

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 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 involving 882 participants with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), pembrolizumab alone significantly improved overall survival compared to cetuximab with chemotherapy, especially in patients with high PD-L1 expression (CPS of 20 or more).

Pembrolizumab combined with chemotherapy also showed improved overall survival compared to cetuximab with chemotherapy across all populations, indicating that pembrolizumab is an effective first-line treatment option for HNSCC, particularly for those with PD-L1 positivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Burtness, B., Harrington, KJ., Greil, R., et al.[2021]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT04643379

Study Details | NCT04643379 | Olaparib in Combination ... In this study, patients with recurrent or metastatic head and neck squamous cell carcinoma will receive first line treatment with olaparib, pembrolizumab, ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40832450/

Olaparib, Pembrolizumab, and Carboplatin as First-Line ... Olaparib, pembrolizumab, and carboplatin given as first-line treatment of RM-HNSCC resulted in a higher ORR than that historically reported ...

4. withpower.com withpower.com/trial/phase-3-squamous-cell-carcinoma-of-head-and-neck-7-2021-ac4a2

Olaparib + Pembrolizumab + Carboplatin for Head and ... Research shows that pembrolizumab, one of the drugs in the combination, has been effective in treating head and neck cancer, especially in cases where the ...

5. 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 ...

6. merck.com merck.com/news/keytruda-pembrolizumab-plus-chemotherapy-with-or-without-bevacizumab-reduced-risk-of-disease-progression-or-death-versus-chemotherapy-with-or-without-bevacizumab-in-certain-patients-with-plati/

KEYTRUDA® (pembrolizumab) Plus Chemotherapy With ... Head and Neck Squamous Cell Cancer KEYTRUDA is indicated for the treatment of adult patients with resectable locally advanced head and neck ...