Valemetostat + Pembrolizumab for Lung Cancer

Recruiting in Palo Alto (17 mi)

+40 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Daiichi Sankyo

Must not be taking: Immunosuppressants, Steroids, Live vaccines

Disqualifiers: Autoimmune disease, CNS metastases, Cardiovascular disease, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This study will compare Valemetostat Tosylate Plus Pembrolizumab vs Pembrolizumab Alone in First-line NSCLC Without Actionable Genomic Alterations

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or high-dose steroids, you may need to adjust your treatment. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Pembrolizumab for lung cancer?

Research shows that Pembrolizumab, a drug that helps the immune system fight cancer, has improved survival in patients with advanced non-small-cell lung cancer, especially when the cancer cells have a specific protein called PD-L1.

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Is the combination of Valemetostat and Pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been studied in various trials for lung cancer and other conditions, showing it is generally safe for humans. It is approved for treating certain types of lung cancer, and studies have shown it to be safe when used alone. However, specific safety data for the combination with Valemetostat is not provided in the available research.

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What makes the drug combination of Valemetostat and Pembrolizumab unique for lung cancer?

This drug combination is unique because it combines Pembrolizumab, an immune system booster that targets PD-1 proteins on cancer cells, with Valemetostat, which may inhibit cancer cell growth by targeting specific enzymes. This approach could offer a novel way to treat lung cancer by using both immune system activation and direct cancer cell inhibition.

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Eligibility Criteria

Adults diagnosed with advanced non-small cell lung cancer (NSCLC) without certain genetic changes, who haven't had systemic therapy for their condition. They must have a high PD-L1 expression and no history of smoking or be under 40 if they have squamous NSCLC. Participants need measurable disease on scans and must provide tissue samples unless prohibited by law.

Inclusion Criteria

I have signed the informed consent form.

I am at least 18 years old or meet the legal age for consent in my area.

I have not received any systemic therapy for my advanced or metastatic disease.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive pembrolizumab and valemetostat tosylate with dose escalation to determine the recommended phase 2 dose

3 weeks

Weekly visits for dose escalation monitoring

Dose Expansion

Participants receive pembrolizumab and valemetostat tosylate at the recommended phase 2 dose

Up to 31 months

Visits every 3 weeks for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Participant Groups

The trial is testing Valemetostat Tosylate combined with Pembrolizumab against Pembrolizumab alone in patients with first-line NSCLC that lacks specific genomic alterations. The goal is to see if adding Valemetostat improves treatment outcomes compared to just using Pembrolizumab.

Group I: Phase 2: Pembrolizumab + Valemetostat Tosylate Experimental Treatment 2 Interventions

Participants will be provided with pembrolizumab at standard dose of 200 mg IV Q3W, and valemetostat will be provided per recommended phase 2 dose (RP2D)

Group II: Phase 1b: Pembrolizumab + Valemetostat Tosylate Experimental Treatment 2 Interventions

Participants will be provided with pembrolizumab at standard dose of 200 mg intravenously (IV) Q3W, and valemetostat will be provided per a dose escalation schedule, with an initial starting dose of 150 mg by mouth once daily.

Group III: Phase 2: Pembrolizumab Active Control 1 Intervention

Participants will be provided with pembrolizumab at standard dose of 200 mg IV Q3W

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of California San Diego (Ucsd)-Moores Cancer Center La Jolla, CA

California Research Institute Los Angeles, CA

Valkyrie Clinical Trials Los Angeles, CA

Mayo Clinic Hospital Jacksonville, FL

More Trial Locations

Who Is Running the Clinical Trial?

Daiichi Sankyo Lead Sponsor

Merck Sharp & Dohme LLC Industry Sponsor

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022] A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.

2. United States pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022] Pembrolizumab is a programmed death receptor-1 masking antibody approved for metastatic non-small cell lung cancer. This Phase 2 study (NCT02818920) of neoadjuvant pembrolizumab in non-small cell lung cancer had a primary end point of safety and secondary end points of efficacy and correlative science.

3. England pubmed.ncbi.nlm.nih.gov

Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial. [2023] In KEYNOTE-010, pembrolizumab versus docetaxel improved overall survival (OS) in patients with programmed death-1 protein (PD)-L1-positive advanced non-small-cell lung cancer (NSCLC). A prespecified exploratory analysis compared outcomes in patients based on PD-L1 expression in archival versus newly collected tumor samples using recently updated survival data.

4. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017] New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.

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

Pembrolizumab in patients with advanced non-small-cell lung cancer (KEYNOTE-001): 3-year results from an open-label, phase 1 study. [2022] The anti-programmed death 1 monoclonal antibody pembrolizumab has shown antitumour activity and is a first-line and second-line treatment option for patients with programmed death ligand 1 (PD-L1)-expressing advanced non-small-cell lung cancer. We report updated 3-year safety and efficacy outcomes from the phase 1 study, KEYNOTE-001.

6. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017] Pembrolizumab, a humanized monoclonal antibody IgG4 anti-PD-1, having offered promising results in patients suffering from non-small cell lung cancer metastatic and heavily pretreated.

7. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020] The emergence of immune checkpoint inhibitors marked an important advancement in the development of cancer therapeutics. Pembrolizumab is a selective humanized IgG4 kappa monoclonal antibody that inhibits the programmed death-1 (PD-1) receptor, an integral component of immune checkpoint regulation in the tumor microenvironment. The drug is currently approved by the Food and Drug Administration for the treatment of advanced melanoma and metastatic squamous and nonsquamous non-small cell lung cancer (NSCLC). Several published studies demonstrate that single-agent pembrolizumab is safe and has efficacy in patients with NSCLC. Many ongoing protocols are investigating the role of pembrolizumab in combination with other agents in lung cancer and various other cancer types. We review the available data on pembrolizumab in NSCLC and examine the role of potential predictive biomarkers of response to therapy.

8. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. [2022] Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1).

9. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. [2023] Pembrolizumab is a programmed cell death protein-1 (PD-1) inhibitor used to treat advanced patients with non-small cell lung cancer (NSCLC) with a programmed cell death ligand-1 (PD-L1) tumour proportion score (TPS) ≥50. Further sub-division of TPS-based stratification has not been evaluated in the UK, although smoking-induced tumour mutational burden and the immunogenic effects of prior radiotherapy are suggested to improve response.

10. Germany pubmed.ncbi.nlm.nih.gov

Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50. [2020] Single-agent pembrolizumab represents the standard first-line option for metastatic non-small-cell lung cancer (NSCLC) patients with a PD-L1 (programmed death-ligand 1) expression of ≥ 50%.