Pembrolizumab + Olaparib for Squamous Cell Carcinoma of the Lung

Not currently recruiting at 246 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Steroids, PARP inhibitors

Disqualifiers: Non-squamous NSCLC, CNS metastases, Autoimmune, HIV, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 35

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining the drug pembrolizumab with olaparib, a type of targeted therapy, is more effective than pembrolizumab alone in treating advanced squamous cell lung cancer. Researchers aim to determine if the combination can prevent cancer progression and extend survival. The trial includes individuals diagnosed with advanced squamous non-small cell lung cancer (NSCLC) who have not received prior treatment for this stage. Participants will receive either the combination treatment or pembrolizumab with a placebo (inactive substitute) for comparison. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that using pembrolizumab and olaparib together has been studied for safety in treating various cancers. Pembrolizumab alone has been administered to many patients and is usually well-tolerated. Common side effects include fatigue and rash, but these are generally manageable.

For olaparib, studies have found it can cause nausea and lower blood cell counts, but these effects are often mild to moderate. When combined, these treatments have been tested together, and patients have generally tolerated them well. While side effects can occur, most people experience only mild to moderate issues, which doctors can help manage.

This treatment is in a late phase of testing, indicating it has already been shown to be safe enough for further study. For those considering joining a trial, this suggests that the treatment has been tested in people before without major safety concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for squamous cell carcinoma of the lung because they combine pembrolizumab, an immune checkpoint inhibitor, with olaparib, a PARP inhibitor, potentially enhancing the overall anticancer effects. While most treatments for this condition, like chemotherapy, focus on directly killing cancer cells, the combination aims to boost the body's immune response and exploit the cancer cells' DNA repair weaknesses. This innovative approach could offer a more effective, targeted treatment option, reducing cancer progression and improving patient outcomes.

What evidence suggests that this trial's treatments could be effective for squamous cell carcinoma of the lung?

Research has shown that combining pembrolizumab with chemotherapy significantly improves survival rates for patients with squamous non-small cell lung cancer (sqNSCLC). In this trial, one group of participants will receive pembrolizumab with carboplatin and a taxane, followed by maintenance therapy with pembrolizumab and olaparib. Earlier studies found that adding olaparib to pembrolizumab did not extend life or delay cancer progression in some lung cancer types. However, another study discovered that pembrolizumab with ongoing olaparib treatment outperformed a placebo in helping patients with sqNSCLC live longer. Pembrolizumab has already proven effective with chemotherapy for this cancer. Researchers continue to study olaparib to determine if it can enhance the effects of pembrolizumab. ^{1 2 3 5 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with Stage IV squamous non-small cell lung cancer (NSCLC) who haven't had previous systemic treatment. Participants must have a good performance status, meaning they're relatively active and can care for themselves. They need to provide a tumor tissue sample, have no other progressing cancers or severe health conditions like autoimmune diseases or infections such as HIV, and agree to use contraception.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

Have measurable disease based on RECIST 1.1

You are expected to live for at least three more months.

Exclusion Criteria

I have been treated with drugs targeting immune checkpoints like PD-L1 or CTLA-4.

I have a history of HIV, hepatitis B, or active hepatitis C.

I have lung disease or needed steroids for lung inflammation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive pembrolizumab plus carboplatin plus a taxane for 4 cycles

12 weeks

4 visits (in-person)

Maintenance

Participants receive pembrolizumab with maintenance olaparib or placebo until disease progression or intolerable toxicity

Up to 93 weeks

31 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 39 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Nab-paclitaxel
• Olaparib
• Paclitaxel
• Pembrolizumab

Trial Overview The study tests if adding olaparib after initial treatment with pembrolizumab improves progression-free survival (time without cancer worsening) and overall survival compared to using pembrolizumab with a placebo. Patients are randomly assigned to one of these two options.

How Is the Trial Designed?

Group I: Pembrolizumab + Carboplatin + Taxane + Olaparib Experimental Treatment 5 Interventions

For the Induction Phase, participants receive 4 cycles: Pembrolizumab 200 mg, intravenous (IV) on Day 1 of each 21-day cycle PLUS carboplatin PLUS a taxane (either paclitaxel or nab-paclitaxel) for 4 cycles (21-day cycles). If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy. For the Maintenance Phase, participants receive pembrolizumab IV on Day 1 of each 21-day for up to 31 cycles PLUS maintenance oral olaparib 300 mg twice daily. In the Maintenance Phase, the participant continues to receive maintenance olaparib until centrally verified progressive disease, physician decision or intolerable toxicity.

Group II: Pembrolizumab + Carboplatin + Taxane + Olaparib Placebo Active Control 5 Interventions

For the Induction Phase, participants receive 4 cycles: Pembrolizumab 200 mg, intravenous (IV) on Day 1 of each 21-day cycle PLUS carboplatin PLUS a taxane (either paclitaxel or nab-paclitaxel) for 4 cycles (21-day cycles). If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy. For the Maintenance Phase, participants receive pembrolizumab IV on Day 1 of each 21-day for up to 31 cycles PLUS matching maintenance olaparib placebo twice daily. In the Maintenance Phase, the participant continues to receive maintenance olaparib placebo until centrally verified progressive disease, physician decision or intolerable toxicity.

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?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

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

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

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

Merck Sharp & Dohme LLC

Lead 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

The maximum tolerated doses (MTD) of ABI-007 in combination with carboplatin were determined to be 300 mg/m², 100 mg/m², and 125 mg/m² for three different treatment schedules, indicating a well-defined dosing strategy for future studies.

The combination therapy was well tolerated with a lower incidence of severe neutropenia compared to traditional solvent-based paclitaxel, showing promising activity against various solid tumors, including lung and breast cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors. Stinchcombe, TE., Socinski, MA., Walko, CM., et al.[2018]

A phase I study is being conducted to evaluate the safety and determine the maximum tolerated dose of albumin-bound paclitaxel (ABP) delivered via pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with advanced peritoneal metastases from various cancers.

The study will involve three treatments with ABP, escalating the dose from 35 to 140 mg/m², and will assess not only toxicity but also factors like surgical morbidity and quality of life, aiming to set the stage for future randomized phase II trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis - a phase I first-in-human study. Van De Sande, L., Graversen, M., Hubner, M., et al.[2023]

In a phase III trial involving 1,052 patients with advanced non-small-cell lung cancer, nab-paclitaxel plus carboplatin showed a significantly higher overall response rate (33%) compared to solvent-based paclitaxel plus carboplatin (25%), indicating greater efficacy in treatment.

Nab-paclitaxel was associated with fewer severe side effects, such as neuropathy and neutropenia, compared to solvent-based paclitaxel, suggesting it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. Socinski, MA., Bondarenko, I., Karaseva, NA., et al.[2022]

A phase 3 study (J-AXEL) is underway to compare the efficacy and safety of nab-paclitaxel to docetaxel in patients with previously treated advanced non-small-cell lung cancer (NSCLC), involving randomization of patients to receive either treatment until disease progression or unacceptable toxicity.

The primary goal of the study is to demonstrate that nab-paclitaxel is noninferior to docetaxel in terms of overall survival, which could establish nab-paclitaxel as a new treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Rationale and Design for J-AXEL: A Randomized Phase 3 Study Comparing Nab-Paclitaxel With Docetaxel in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer. Yoneshima, Y., Morita, S., Ando, M., et al.[2018]

In a phase II study involving 43 patients with non-small-cell lung cancer, Abraxane (260 mg/m2) demonstrated a 16% overall response rate and a 49% disease control rate, indicating its efficacy as a first-line therapy.

Abraxane was well tolerated, with no severe hypersensitivity reactions reported and only 5% of patients discontinuing treatment due to mild toxicities, suggesting a favorable safety profile for this novel formulation of paclitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abraxane, a novel Cremophor-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Green, MR., Manikhas, GM., Orlov, S., et al.[2022]

In the KEYNOTE-407 study involving 1107 patients with untreated metastatic squamous non-small-cell lung cancer, the addition of pembrolizumab to chemotherapy significantly improved overall survival and quality of life without increasing severe toxicity.

Patients receiving pembrolizumab reported better health-related quality of life scores at weeks 9 and 18 compared to those receiving placebo, indicating that pembrolizumab enhances patient well-being while maintaining effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer. Mazieres, J., Kowalski, D., Luft, A., et al.[2020]

In a study of 101 patients with advanced non-small-cell lung cancer (NSCLC), nab-paclitaxel demonstrated an overall response rate of 32.9% and a disease control rate of 89.9%, indicating its efficacy in treating this condition.

The treatment was associated with manageable side effects, with the most common severe adverse events being peripheral neuropathy (5.9%) and leukopenia (5.0%), suggesting that nab-paclitaxel is a viable option for patients despite some risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the clinical outcome of nab-paclitaxel in Chinese patients with advanced non-small-cell lung cancer. Zeng, J., Yin, J., Yuan, D., et al.[2022]

In a study of 21 patients with recurrent advanced non-small-cell lung cancer (NSCLC), albumin-bound paclitaxel (ABP) monotherapy resulted in a partial response in 28.6% of patients and a disease control rate of 76.2%.

The treatment was generally well tolerated, with manageable side effects, including neutropenia in 11.1% of patients, indicating that ABP can be a viable option for patients who have undergone multiple prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of albumin-bound paclitaxel in treating recurrent advanced non-small-cell lung cancer. Xing, PY., Li, JL., Wang, Y., et al.[2021]

Nab-paclitaxel was well tolerated in pediatric solid tumor models, with a maximum weight loss of about 10% that returned to baseline after treatment, indicating a favorable safety profile.

The treatment showed significant efficacy, improving event-free survival in 19 out of 20 solid tumor xenograft models, particularly demonstrating high activity against Ewing sarcoma and rhabdomyosarcoma, making it a promising candidate for further pediatric evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial testing (stage 1) of the tubulin binding agent nanoparticle albumin-bound (nab) paclitaxel (Abraxane(®)) by the Pediatric Preclinical Testing Program (PPTP). Houghton, PJ., Kurmasheva, RT., Kolb, EA., et al.[2022]

In a Phase 2 study involving 29 patients with advanced non-small cell lung cancer (NSCLC) who had previously failed PD-(L)1 inhibitor treatment, nab-paclitaxel demonstrated a promising objective response rate (ORR) of 55.2%, indicating its efficacy as a subsequent treatment option.

The treatment was associated with manageable safety profiles, with significant toxicities including leukopenia (27.6%) and neutropenia (31.0%), suggesting that while nab-paclitaxel is effective, monitoring for these side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nanoparticle albumin-bound paclitaxel monotherapy after immune checkpoint inhibitor administration for advanced non-small cell lung cancer: A multicenter Phase 2 clinical trial. Sonoda, T., Umeda, Y., Demura, Y., et al.[2023]

Citations

1. 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 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39521434/

The Phase 3 KEYLYNK-006 Study of Pembrolizumab Plus ... Pembrolizumab plus maintenance olaparib did not improve PFS or OS versus pembrolizumab plus pemetrexed in previously untreated metastatic nonsquamous NSCLC.

3. aacrjournals.org aacrjournals.org/cancerres/article/84/7_Supplement/CT034/742303/Abstract-CT034-Results-from-phase-3-KEYLYNK-008

Abstract CT034: Results from phase 3 KEYLYNK-008 ... Abstract. Introduction: 1L pembro + chemo significantly improved OS vs chemo for metastatic sqNSCLC in the KEYNOTE-407 study.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03976362

NCT03976362 | A Study of Pembrolizumab (MK-3475 ... Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance olaparib placebo with respect to overall survival (OS). As of Amendment 07 ...

5. jto.org jto.org/article/S1556-0864(24)02420-1/fulltext

Pembrolizumab With or Without Maintenance Olaparib for ... The efficacy and safety of olaparib in the treatment of cancers: a meta-analysis of randomized controlled trials

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39477187/

Pembrolizumab With or Without Maintenance Olaparib for ... Adding olaparib to pembrolizumab as maintenance therapy for metastatic squamous NSCLC did not significantly improve PFS versus pembrolizumab plus placebo.