Pembrolizumab + Olaparib/Pemetrexed for Non-Small Cell Lung Cancer

Not currently recruiting at 263 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Steroids, PARP inhibitors

Disqualifiers: Squamous NSCLC, CNS metastases, Autoimmune, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 35

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining pembrolizumab (an immunotherapy drug) with either olaparib (a targeted therapy) or pemetrexed (a chemotherapy drug) is more effective for treating non-small cell lung cancer (NSCLC) that isn't squamous cell type. Researchers seek to identify which combination extends patient survival and prevents cancer growth. Suitable participants have stage IV NSCLC, have not received prior treatment for advanced NSCLC, and have a type of the disease where specific therapies aren't recommended. As a Phase 3 trial, this study represents the final step before FDA approval, providing patients an opportunity to access potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should not have received prior systemic treatment for their advanced/metastatic NSCLC.

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

Research shows that combining pembrolizumab with olaparib does not harm overall quality of life, making the treatment generally easy to handle. Previous studies have not identified any major safety concerns with this combination.

For pembrolizumab with pemetrexed, studies consistently show it to be well-tolerated for non-small cell lung cancer. This combination already serves as a standard treatment for some lung cancer patients, indicating its safety.

Various studies have tested both combinations without major safety issues, suggesting promising tolerability. Participants considering this trial can feel reassured by the existing safety data for these treatment options. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for non-small cell lung cancer because they combine pembrolizumab, a type of immunotherapy, with other drugs like olaparib or pemetrexed. Pembrolizumab works by blocking a protein that prevents the immune system from attacking cancer cells, allowing the body to fight the cancer more effectively. When combined with olaparib, a PARP inhibitor, it may enhance cancer cell death, especially in cancers with specific genetic mutations. Meanwhile, combining pembrolizumab with pemetrexed and platinum chemotherapy could offer a more comprehensive attack on the cancer by using both the immune system and traditional chemotherapy. These combinations might lead to more effective treatments with the potential for longer-lasting results compared to standard therapies.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that using pembrolizumab with pemetrexed may help treat non-small cell lung cancer (NSCLC). One study found that patients receiving pembrolizumab with pemetrexed and platinum-based chemotherapy had a five-year survival rate of about 19.4%, indicating a lasting survival benefit compared to chemotherapy alone. In this trial, one arm will test the combination of pembrolizumab, pemetrexed, and platinum therapy, while another arm will include olaparib in the maintenance phase. Previous evidence suggests that adding olaparib to pembrolizumab did not improve progression-free survival or overall survival. The evidence supports pembrolizumab and pemetrexed as an effective treatment option for NSCLC. ^{1 3 4 6 7}

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 nonsquamous NSCLC who haven't had prior treatments. They must have a life expectancy of at least 3 months, be able to use contraception, and not be pregnant. Participants need good organ function and no severe allergies to the drugs being tested or their ingredients.

Inclusion Criteria

I haven't had systemic treatment for my advanced lung cancer.

My lung cancer is advanced (stage IV) and not squamous.

I have provided a biopsy sample of my tumor that has not been treated with radiation.

Exclusion Criteria

I have been treated for an autoimmune disease in the last 2 years.

You have had a serious allergic reaction (Grade 3 or higher) to pembrolizumab or any of its ingredients.

My lung cancer is mainly squamous cell type.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive pembrolizumab plus pemetrexed plus platinum chemotherapy for up to 4 cycles

12 weeks

4 visits (in-person)

Maintenance

Participants receive pembrolizumab plus maintenance olaparib or maintenance pemetrexed for up to 31 cycles

93 weeks

31 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Second Course (optional)

Eligible participants may receive a second course of pembrolizumab for up to 17 cycles

51 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib
• Pembrolizumab
• Pemetrexed

Trial Overview The study compares two treatments: pembrolizumab combined with olaparib versus pembrolizumab with pemetrexed after initial therapy. It aims to see which combination is better for extending patients' lives without cancer progression and overall survival.

How Is the Trial Designed?

Group I: Pembrolizumab + Pemetrexed + Platinum Therapy + Olaparib Experimental Treatment 5 Interventions

For the Induction Phase, participants receive 4 cycles (up to \~12 weeks \[cycle = 3 weeks\]): pembrolizumab 200 mg intravenous (IV) on Day 1 of each cycle (cycles 1 through 4) PLUS pemetrexed 500 mg/m\^2 IV on Day 1 of each cycle (cycles 1 through 4) PLUS platinum chemotherapy, investigator's choice: carboplatin area under the curve (AUC) 5 mg/mL/min IV on Day 1 of each cycle (Cycles 1 through 4) OR cisplatin 75 mg/m\^2 IV on Day 1 of each cycle (Cycles 1 through 4). If the participant has a complete/partial response or stable disease to induction therapy, the participant can enter the Maintenance Phase and receive pembrolizumab 200 mg IV on Day 1 of each 3-week cycle for up to 31 cycles PLUS maintenance oral olaparib 300 mg twice daily. The participant can continue to receive maintenance olaparib until progressive disease or toxicity. Across both phases, participants can receive pembrolizumab for a total treatment duration of up to \~35 cycles (up to \~2 years \[cycle = 3 weeks\]).

Group II: Pembrolizumab + Pemetrexed + Platinum Therapy + Pemetrexed Active Control 4 Interventions

For the Induction Phase, participants receive 4 cycles (up to \~12 weeks \[cycle = 3 weeks\]): pembrolizumab 200 mg IV on Day 1 of each cycle (cycles 1 through 4) PLUS pemetrexed 500 mg/m\^2 IV on Day 1 of each cycle (cycles 1 through 4) PLUS platinum chemotherapy, investigator's choice: carboplatin AUC 5 mg/mL/min IV on Day 1 of each cycle (Cycles 1 through 4) OR cisplatin 75 mg/m\^2 IV on Day 1 of each cycle (Cycles 1 through 4). If the participant has a complete/partial response or stable disease to induction therapy, the participant can enter the Maintenance Phase and receive pembrolizumab 200 mg IV on Day 1 of each 3-week cycle for up to 31 cycles PLUS maintenance pemetrexed 500 mg/m\^2 IV on Day 1 of each 3-week cycle. The participant can continue to receive maintenance pemetrexed until progressive disease or toxicity. Across both phases, participants can receive pembrolizumab for a total treatment duration of up to \~35 cycles (up to \~2 years \[cycle = 3 weeks\]).

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

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

In a study of 97 non-small cell lung cancer patients treated with pembrolizumab, 40% experienced treatment-related adverse events (trAEs), with common ones being rash, fatigue, and hypothyroidism.

Patients who experienced trAEs had significantly better clinical outcomes, including a higher objective response rate (38.5% vs. 8.9%), longer progression-free survival (248 days vs. 60 days), and longer overall survival (493 days vs. 144.5 days), suggesting that trAEs may be indicative of a positive response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-Related Adverse Events Predict Improved Clinical Outcome in NSCLC Patients on KEYNOTE-001 at a Single Center. Lisberg, A., Tucker, DA., Goldman, JW., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

In a study of 1,026 treatment-naïve patients with metastatic non-small-cell lung cancer (NSCLC) and PD-L1 expression of ≥50%, pembrolizumab showed an objective response rate of 44.5%, with median progression-free survival of 7.9 months and overall survival of 17.2 months.

Higher PD-L1 expression (≥90%) was linked to better treatment outcomes, while factors like poor performance status and the presence of bone or liver metastases were associated with worse clinical outcomes, indicating the importance of patient selection for pembrolizumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50. Cortellini, A., Tiseo, M., Banna, GL., et al.[2020]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

In a long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.

Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. Awad, MM., Gadgeel, SM., Borghaei, H., et al.[2021]

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

In the KEYNOTE-024 study involving 305 patients with untreated advanced non-small-cell lung cancer, pembrolizumab significantly improved overall survival (OS) compared to platinum-based chemotherapy, with a median OS of 30.0 months versus 14.2 months for chemotherapy.

Pembrolizumab also had a better safety profile, with fewer treatment-related severe adverse events (31.2% for pembrolizumab vs. 53.3% for chemotherapy), indicating it is a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Citations

1. 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.

2. 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

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 ... “These results are an important reminder of how challenging it may be to treat these patients with metastatic nonsquamous non-small cell lung ...

4. 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 ... Introduction: 1L pembro + chemo significantly improved OS vs chemo for metastatic sqNSCLC in the KEYNOTE-407 study.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1556086424024201

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.

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.

7. 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 ...