Valemetostat + Pembrolizumab for Lung Cancer

Recruiting at 66 trial locations

Overseen By Contact for Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Daiichi Sankyo

Must not be taking: Immunosuppressants, Steroids, Live vaccines

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

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

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

Compensation: Varies

Number of Visits: 3

137 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of combining Valemetostat Tosylate, a new potential drug, with Pembrolizumab, an immunotherapy drug, compared to using only Pembrolizumab for treating advanced non-small cell lung cancer (NSCLC) without certain genetic changes. The researchers seek to determine if the combination is more effective for individuals who have not yet received systemic treatment for their advanced lung cancer. The trial is recruiting participants with specific types of NSCLC that lack genetic changes such as EGFR, ALK, or ROS1, and whose tumors exhibit high levels of the protein PD-L1. Individuals with advanced or recurring lung cancer fitting this profile may find this trial suitable. As a Phase 1, Phase 2 trial, the research focuses on understanding the treatment's effects in people and assessing its effectiveness in an initial, smaller group.

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.

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

Research is examining the safety and effectiveness of using Valemetostat Tosylate with Pembrolizumab for lung cancer treatment. Earlier studies have shown that Valemetostat is generally safe when used alone for certain lung cancer types. However, specific safety information about its use with Pembrolizumab remains limited.

Pembrolizumab is a well-known cancer treatment and is usually well-tolerated. Common side effects include fatigue, rash, and diarrhea, but these are typically manageable.

As this combination treatment is still under study, researchers continue to gather safety information. Participation in this study will help researchers understand how patients handle the combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of valemetostat and pembrolizumab for lung cancer because it introduces a novel approach to treatment. Most current lung cancer treatments, like chemotherapy or traditional immunotherapies, target cancer cells directly or enhance the immune response. However, valemetostat is a dual EZH1/2 inhibitor, which means it targets specific enzymes that play a role in cancer cell growth and survival, potentially overcoming resistance seen with standard treatments. When combined with pembrolizumab, a well-known immunotherapy, this treatment aims to enhance the body's immune response against cancer cells more effectively. This unique mechanism could offer new hope for patients who don't respond well to existing treatment options.

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

Research has shown that pembrolizumab effectively treats lung cancer, particularly in patients with specific tumor types. In this trial, some participants will receive pembrolizumab alone, while others will receive it in combination with valemetostat tosylate. Researchers are testing valemetostat tosylate with pembrolizumab to determine if it enhances the treatment's effectiveness. Early results suggest that this combination might outperform pembrolizumab alone. In other cancers, such as head and neck cancer, pembrolizumab alone has not been as successful, highlighting the need for improved treatment combinations. The combination of valemetostat and pembrolizumab aims to address these challenges by targeting cancer cells more effectively. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Valemetostat Tosylate

Trial Overview 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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

Daiichi Sankyo

Lead Sponsor

Trials

443

Recruited

493,000+

Hiroyuki Okuzawa

Daiichi Sankyo

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Yuki Abe

Daiichi Sankyo

Chief Medical Officer since 2023

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

Published Research Related to This Trial

In a study of 100 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, further stratification of PD-L1 tumor proportion score (TPS) beyond 50% did not significantly affect progression-free survival (PFS).

Smoking status was associated with improved PFS, while prior radiotherapy was linked to decreased PFS, indicating that these factors, along with performance status, may serve as important biomarkers for predicting response to pembrolizumab treatment.

NCBI (Pubmed)

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. Mander, ES., Merrick, CB., Nicholson, HA., et al.[2023]

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 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 study of 550 patients with advanced non-small-cell lung cancer, pembrolizumab demonstrated a 41% objective response rate in treatment-naive patients and a 23% response rate in previously treated patients, indicating its efficacy as a treatment option.

The median overall survival was significantly longer for treatment-naive patients (22.3 months) compared to previously treated patients (10.5 months), with safety data showing that only 12% experienced grade 3-5 treatment-related adverse events, suggesting a tolerable safety profile.

NCBI (Pubmed)

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. Leighl, NB., Hellmann, MD., Hui, R., 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 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC) expressing PD-L1, pembrolizumab significantly improved median progression-free survival to 10.3 months compared to 6.0 months with chemotherapy, indicating its efficacy as a treatment option.

Patients receiving pembrolizumab also experienced fewer treatment-related adverse events (73.4% vs. 90.0% for chemotherapy), highlighting its safety profile alongside its effectiveness in prolonging survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

In a study involving 1033 patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved overall survival compared to docetaxel, with a hazard ratio of 0.66, indicating a 34% reduction in the risk of death.

The effectiveness of pembrolizumab was consistent across both archival and newly collected tumor samples, with better outcomes observed in patients with higher PD-L1 expression (TPS ≥50%), showing hazard ratios of 0.64 and 0.40 for overall survival, respectively.

NCBI (Pubmed)

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. Herbst, RS., Baas, P., Perez-Gracia, JL., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06644768

NCT06644768 | A Study of Valemetostat Tosylate Plus ... This trial will evaluate the safety and efficacy of valemetostat tosylate (DS-3201b) in combination with fixed-dose pembrolizumab versus pembrolizumab alone ...

2. datasourcebydaiichisankyo.com datasourcebydaiichisankyo.com/en/clinical-trials/-/view/study/NCT06644768

Clinical Trials A Study of Valemetostat Tosylate Plus Pembrolizumab Versus Pembrolizumab Alone in First-Line NSCLC Without Actionable Genomic Alterations.

3. datasourcebydaiichisankyo.com datasourcebydaiichisankyo.com/documents/d/datahub/jsmo-2025_val_yamamoto_poster_final

Valemetostat Plus Pembrolizumab in 1L NSCLC Without ... assessment of phase 1b data, including safety, efficacy, and available pharmacokinetic and biomarker data. – Preliminary clinical activity will also be assessed.

4. withpower.com withpower.com/trial/phase-2-carcinoma-non-small-cell-lung-10-2024-be5ce

Valemetostat + Pembrolizumab for Lung Cancer The effectiveness of pembrolizumab was consistent across both archival and newly collected tumor samples, with better outcomes observed in patients with higher ...

5. reporter.nih.gov reporter.nih.gov/search/13EBCA09468FC1D27598B8961CAA4A01A2FFCEB861BF/project-details/11188443

Valemetostat in combination with pembrolizumab in head ... Patients with R/M pembrolizumab-naïve HPV-negative HNSCC have a low 6-month progression-free survival (PFS) (28%) with pembrolizumab monotherapy, thus novel ...

6. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT06644768

A Study of Valemetostat Tosylate Plus Pembrolizumab Versus ... This study will compare Valemetostat Tosylate Plus Pembrolizumab vs Pembrolizumab Alone in First-line NSCLC Without Actionable Genomic Alterations.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11371507/

A phase I/II study of valemetostat (DS-3201b), an EZH1/2 ... Valemetostat, combined with agents without overlapping toxicity, warrants further investigation in SCLC. Keywords: Small cell lung cancer, SLFN11, irinotecan ...