Pembrolizumab + Epigenetic Drugs for Lung Cancer

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Anti-PD1/PD-L1

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: EGFR/ALK mutations, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three drugs—pembrolizumab (an immunotherapy drug), guadecitabine, and mocetinostat—to determine their safety and effectiveness in treating advanced lung cancer. The goal is to understand how these drugs work together and identify potential side effects. It suits individuals with stage IIIb or IV non-small cell lung cancer who have previously tried treatments targeting PD-1 or PD-L1 proteins but experienced cancer progression. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have any systemic anti-cancer therapy within 3 weeks before starting the trial, and certain other treatments may also need to be paused. It's best to discuss your specific medications with the trial team.

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

Research shows that pembrolizumab, guadecitabine, and mocetinostat are being tested together to assess their safety in treating lung cancer. Pembrolizumab is already used for some cancers, providing extensive safety data. However, combining it with guadecitabine and mocetinostat is a new approach. Current studies focus on determining the best doses of guadecitabine and mocetinostat to ensure safe combination with pembrolizumab.

As this is an early-phase study, researchers primarily evaluate how well participants tolerate these drugs together. At this stage, common side effects are closely monitored to ensure they remain manageable. While detailed information on side effects is not yet available, the goal is to understand any reactions and adjust doses to minimize risks. Prospective participants should know that safety is a top priority, with potential side effects carefully tracked and managed. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab, guadecitabine, and mocetinostat for lung cancer because it introduces a novel approach by combining an immunotherapy with epigenetic drugs. Unlike standard treatments like chemotherapy, which directly target and kill cancer cells, this combination enhances the immune system's ability to recognize and attack cancer cells by altering gene expression. Pembrolizumab is an immune checkpoint inhibitor that unleashes the immune system, while guadecitabine and mocetinostat modify the cancer cells' genetic environment, potentially making them more susceptible to immune attacks. This multi-faceted approach could offer a more effective way to tackle lung cancer, especially in cases where traditional treatments fall short.

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

Research has shown that pembrolizumab effectively treats lung cancer by boosting the immune system to fight cancer cells. In this trial, participants will receive a combination of pembrolizumab, guadecitabine, and mocetinostat. Guadecitabine and mocetinostat may enhance pembrolizumab's effect by helping the immune system recognize cancer cells more clearly. Early results suggest that using these drugs together could improve outcomes for lung cancer patients. Although more research is needed, this combination appears promising in strengthening the body's fight against cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Kathryn Arbour, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with advanced stage IIIb or IV NSCLC who have previously been treated with anti-PD1/PD-L1 therapy and experienced disease progression. Participants must be able to undergo biopsies, have an ECOG performance status of 0-1, and adequate organ function. Women must test negative for pregnancy and use effective contraception.

Inclusion Criteria

My cancer tissue sample was taken through a core biopsy.

My lung cancer is at stage IIIb or IV.

I am able and willing to sign the consent form.

Exclusion Criteria

I am currently on medication for an infection.

Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment

You have a history of autoimmune disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab, guadecitabine, and mocetinostat to assess safety and efficacy

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Guadecitabine
• Mocetinostat
• Pembrolizumab

Trial Overview The trial is testing the safety of combining pembrolizumab (an immunotherapy drug) with guadecitabine and mocetinostat (epigenetic drugs). The goal is to determine the effects on lung cancer treatment and identify any side effects at various doses.

How Is the Trial Designed?

Group I: pembrolizumab plus guadecitabine and mocetinostat Experimental Treatment 3 Interventions

Pembrolizumab given IV; guadecitabine given SQ, mocetinostat given PO.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Mirati Therapeutics Inc.

Industry Sponsor

Trials

73

Recruited

8,900+

Dr. Charles M. Baum

Mirati Therapeutics Inc.

Chief Executive Officer since 2023

MD, PhD

Dr. Joseph Leveque

Mirati Therapeutics Inc.

Chief Medical Officer since 2021

MD

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

Stand Up To Cancer

Collaborator

Trials

53

Recruited

40,100+

Astex Pharmaceuticals, Inc.

Industry Sponsor

Trials

97

Recruited

7,400+

Dr. Harren Jhoti

Astex Pharmaceuticals, Inc.

Chief Executive Officer since 2007

PhD in Biochemistry from Birkbeck College, London

Dr. Harold N. Keer

Astex Pharmaceuticals, Inc.

Chief Medical Officer since 2020

MD

Van Andel Research Institute

Collaborator

Trials

28

Recruited

5,200+

Published Research Related to This Trial

In the phase Ib KEYNOTE-001 study, pembrolizumab monotherapy showed durable antitumor activity in advanced non-small-cell lung cancer (NSCLC), with a median overall survival (OS) of 22.3 months for treatment-naive patients and 10.5 months for previously treated patients, and 5-year OS rates of 23.2% and 15.5%, respectively.

Patients with a PD-L1 tumor proportion score of 50% or greater had even better outcomes, with 5-year OS rates of 29.6% for treatment-naive and 25.0% for previously treated patients, while the treatment maintained a favorable safety profile with minimal late-onset adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-Year Overall Survival for Patients With Advanced Non‒Small-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study. Garon, EB., Hellmann, MD., Rizvi, NA., et al.[2022]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

In a phase 2 trial involving 100 patients with advanced non-small cell lung cancer, combining pembrolizumab with CC-486 (oral azacitidine) did not show a significant improvement in progression-free survival compared to pembrolizumab with placebo, with median PFS of 2.9 months versus 4.0 months, respectively.

While the combination treatment did not enhance efficacy, it resulted in more treatment-emergent adverse events, particularly gastrointestinal issues, which may have limited the duration and feasibility of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised phase 2 study of pembrolizumab plus CC-486 versus pembrolizumab plus placebo in patients with previously treated advanced non-small cell lung cancer. Levy, BP., Giaccone, G., Besse, B., et al.[2020]

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 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]

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]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

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]

The combination of mocetinostat (70 mg TIW) and durvalumab was generally well tolerated in patients with advanced non-small cell lung cancer (NSCLC), with an objective response rate (ORR) of 11.5% across all phase II cohorts, indicating some effectiveness in this challenging population.

Notably, the treatment showed a higher ORR of 23.1% in patients whose disease was refractory to prior checkpoint inhibitor therapies, suggesting that mocetinostat may help overcome resistance to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mocetinostat in Combination With Durvalumab for Patients With Advanced NSCLC: Results From a Phase I/II Study. Johnson, ML., Strauss, J., Patel, MR., et al.[2023]

The KEYNOTE-001 trial demonstrated that pembrolizumab significantly improves clinical outcomes for patients with advanced non-small cell lung cancer, indicating its efficacy as a treatment option.

Patients whose tumors express PD-L1 in at least 50% of cells showed better responses to pembrolizumab, suggesting that PD-L1 expression is a key factor in predicting treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Shows Promise for NSCLC. [2015]

Citations

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NCT03220477 | Pembrolizumab (Immunotherapy Drug) in ... The purpose of this study is to test the safety of a combination of three drugs, pembrolizumab, guadecitabine and mocetinostat . Pembrolizumab is a drug ...

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Pembrolizumab, Guadecitabine, and Mocetinostat in ... Giving pembrolizumab, guadecitabine, and mocetinostat together may work in treating patients with non-small cell lung cancer. Eligibility Criteria ...

3. lung.org lung.org/research/clinical-trials/find-a-clinical-trial-1/listings/pembrolizumab-immunotherapy

Pembrolizumab (Immunotherapy Drug) in Combination ... The purpose of this study is to find the best dose of the investigational drugs guadecitabine and mocetinostat to be given safely and effectively with ...

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igniting new hope for lung cancer - PMC - PubMed Central - NIH In this review, we will discuss the anti-PD-(L)1 resistance mechanism landscape in NSCLC and four novel modalities of immunotherapy in detail, ...

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NCT03220477 | Pembrolizumab (Immunotherapy Drug) in ... The purpose of this study is to test the safety of a combination of three drugs, pembrolizumab, guadecitabine and mocetinostat. Pembrolizumab is a drug ...