Pembrolizumab + Olaparib for Squamous Cell Carcinoma of the Lung

Recruiting at 177 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

851 Participants Needed

Trial Summary

What is the purpose of this trial?

The current study will compare pembrolizumab (MK-3475) plus maintenance olaparib, vs. pembrolizumab plus maintenance olaparib placebo for the treatment of squamous NSCLC. The study's 2 primary hypotheses are: 1. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance olaparib placebo with respect to progression-free survival (PFS) per RECIST 1.1 by blinded independent clinical review (BICR). 2. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance olaparib placebo with respect to overall survival (OS). As of Amendment 07, there will be no further analyses for OS and patient-reported outcome assessments.

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.

What data supports the effectiveness of the drug combination of Pembrolizumab, Olaparib, and other components for treating Squamous Cell Carcinoma of the Lung?

Research shows that nab-paclitaxel combined with carboplatin is effective in treating non-small-cell lung cancer (NSCLC), which is a similar type of lung cancer. This combination has shown promising results in terms of response rates and safety in various studies. ^{1 2 3 4 5}

Is the combination of Pembrolizumab, Olaparib, and other drugs safe for humans?

Research shows that albumin-bound paclitaxel (nab-paclitaxel) combined with carboplatin has been studied for safety in treating various cancers, including lung cancer. It generally has a different and sometimes lower toxicity profile compared to other formulations, with a lower rate of severe neutropenia (a condition where there is a low count of a type of white blood cell). ^{1 4 6 7 8}

What makes the drug combination of Pembrolizumab and Olaparib unique for treating squamous cell carcinoma of the lung?

This treatment combines Pembrolizumab, an immunotherapy drug that helps the immune system attack cancer cells, with Olaparib, a drug that targets cancer cell DNA repair mechanisms. The use of albumin-bound paclitaxel (Abraxane) in this combination allows for higher drug concentration in tumors with potentially fewer side effects compared to traditional formulations. ^{2 4 9 10 11}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2022]

2. England 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. [2022]

3. United States 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. [2018]

4. Germany 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. [2018]

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

Nab-paclitaxel plus carboplatin as an effective and safe chemotherapy regimen for pulmonary carcinosarcoma with interstitial lung disease: A case report. [2020]

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

Efficacy and safety of albumin-bound paclitaxel in treating recurrent advanced non-small-cell lung cancer. [2021]

7. United States 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). [2022]

8. United States 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. [2023]

9. United States 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. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Assessing the clinical outcome of nab-paclitaxel in Chinese patients with advanced non-small-cell lung cancer. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis - a phase I first-in-human study. [2023]