Phase I Study of Valemetostat and Atezolizumab as Maintenance Therapy for Patients With Extensive-Stage Small Cell Lung Cancer

Plain English Summary

A Study of Valemetostat in Combination With Atezolizumab in People With Lung Cancer is a Phase 1 clinical trial sponsored by Memorial Sloan Kettering Cancer Center studying Extensive-stage Small-cell Lung Cancer. This trial is testing a combination of two drugs, valemetostat and atezolizumab, as a maintenance therapy for patients with extensive-stage small cell lung cancer. It is for adults (18+) with newly diagnosed extensive-stage small cell lung cancer who have responded to initial treatment. Participants will receive valemetostat at different doses and atezolizumab. The study aims to find the safest dose of valemetostat. Alternative treatments may include continued standard chemotherapy, immunotherapy, or other clinical trials. The trial aims to enroll 24 participants.

Official Summary

This study will test whether valemetostat in combination with atezolizumab is a safe treatment that causes few or mild side effects in people with extensive-stage small cell lung cancer (SCLC). The researchers will test different doses of valemetostat to find the highest dose that causes few or mild side effects in participants. After the dose is found, researchers will test it in a new group of participants to learn more about the safety of the study treatment and see if it is an effective treatment for extensive-stage SCLC.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are 18 or older, have a confirmed diagnosis of extensive-stage small cell lung cancer, and have stable disease or a response after 4 cycles of initial platinum doublet chemotherapy with atezolizumab. You cannot join if you have active, uncontrolled systemic diseases, symptomatic brain metastases, or have received certain other cancer treatments recently. Your blood counts, kidney, and liver function must be within specific limits. You must be able to start the study treatment within 4 weeks of finishing your initial therapy. This trial is studying Extensive-stage Small-cell Lung Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome is to find the highest dose of valemetostat that is safe and well-tolerated when given with atezolizumab, which helps researchers determine the best dose for future studies. The specific primary outcome measures are: Determine Phase II dose (RP2D) (1 year). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial addresses a need for new maintenance therapies in extensive-stage small cell lung cancer, aiming to improve outcomes after initial treatment. This research targets Extensive-stage Small-cell Lung Cancer, where improved treatment options are needed.

Investor Insight

This Phase I trial is an early step to evaluate a novel combination therapy, potentially expanding treatment options in a challenging cancer type. Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific doses of valemetostat being tested and how often you will need to take them. Understand that you will have regular blood tests and medical check-ups to monitor for side effects and assess your response to treatment. Be prepared for potential clinic visits for drug administration and monitoring. This trial is currently recruiting participants. The trial is being conducted at 7 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 24 participants

Interventions

• DRUG: Valemetostat — Dose level -1 100 mg po once daily Dose level 1 150 mg po once daily Dose level 2 200 mg po once daily
• DRUG: Atezolizumab — 1680 mg IV q4weeks

Primary Outcomes

• Determine Phase II dose (RP2D) (1 year)

Secondary Outcomes

• Progression-free survival (PFS) (1 year)

Full Eligibility Criteria

Inclusion Criteria:

* Signed informed consent form (ICF)
* Ability to comply with the study protocol as per the investigator's judgment
* Age ≥ 18 years at the time of signing the ICF
* Life expectancy ≥ 12 weeks
* ECOG performance status 0 or 1
* Pathologically confirmed diagnosis of newly diagnosed extensive-stage small cell lung cancer. Patients with a diagnosis of combined small cell lung cancer with other histologies may be considered for inclusion if the predominant histology is SCLC and only after discussion with the study PI.
* Radiographically documented RECIST version 1.1 stable disease, partial or complete response after initial treatment with a platinum doublet regimen in combination with atezolizumab for 4 cycles. It is acceptable to have no measurable disease at the start of this study.
* Must be able to begin therapy within 4 weeks of completing the fourth cycle of chemotherapy and immunotherapy.
* Adequate hematologic and end-organ function, as defined by the following laboratory test results obtained within 14 days prior to initiation of study treatment. Transfusion (red blood cell or platelet) or granulocyte-colony stimulating factor (G-CSF) administration is not allowed within 2 weeks prior to screening laboratory tests:

  o Adequate bone marrow function as defined by:
* Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (1500/µL)
* Hemoglobin ≥ 9 g/dL
* Platelets ≥ 100 x 10\^9/L o Adequate renal function as defined by:
* Creatinine clearance ≥ 30 mL/min as calculated using the Cockcroft-Gault equation

  o Adequate hepatic function as defined by:
* AST, ALT, and alkaline phosphatase (ALP) ≤ 3 x ULN with the following exception:
* Patients with documented liver metastases: AST, ALT and ALP ≤ 5 x ULN

Exclusion Criteria:

* Any active uncontrolled systemic diseases or other medical conditions considered to be poorly controlled by the investigator including but not limited to bleeding diatheses, that could in the investigator's opinion, potentially interfere with completion of study procedures or interpretation of study outcomes.
* Patients who receive consolidative chest radiation after completion of initial chemotherapy and immunotherapy.
* Symptomatic CNS metastases
* Patients with treated CNS metastases are allowed on the study if their clinical symptoms are adequately controlled and the daily dose of steroid use is equivalent to or less than 10 mg of prednisone.
* Receiving concomitant treatment with a moderate or strong inducer of CYP3A within 14 days of first receipt of valemetostat o Consumption of herbs/fruits that may have an influence on PK of valemetostat (strong CYP3A inhibitors or inducers) such as St. John's wort, star fruit, Seville orange or Seville orange-containing foods and beverages, grapefruit or grapefruit-containing food or beverages should be avoided from 14 days prior to the start of the study and throughout the entire study.

Prior exposure to valemetostat or other inhibitors of enhancer of zeste homologue-2 (EZH2)

* Refractory nausea and vomiting, malabsorption, biliary shunt, significant bowel resection, or any other condition that significantly affects gut motility or absorption and would preclude adequate absorption of valemetostat in the opinion of the treating physician and/or PI.
* Currently receiving radiation therapy, or who have received radiation within 2 weeks prior to the initiation of study treatment, or who plan to receive radiation therapy within the safety evaluation period for dose-limiting toxicity during Cycle 1.
* Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE version 5.0, Grade ≤ 1 or baseline.

  o NOTE: Participants may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to Grade \>2 for at least 3 months prior to enrollment and managed with standard of care treatment) that the investigator deems related to previous anticancer therapy, comprised of the following:
* Chemotherapy-induced neuropathy
* Residual toxicities from prior IO treatment: Grade 1 or Grade 2 endocrinopathies which may include:
* Hypothyroidism/ hyperthyroidism
* Type I diabetes
* Hyperglycemia
* Adrenal insufficiency
* Adrenalitis
* Skin hypopigmentation (vitiligo)
* Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia).

  o NOTE: Procedures such as a percutaneous biopsy, pleural catheter insertion, placement of a central venous catheter or other minor procedures are permitted.
* Uncontrolled or significant cardiovascular disease, including the following:
* Evidence of prolongation of QT/QTc interval (e.g., repeated episodes of QT corrected for heart rate using Fridericia's method \[QTcF\] \>470 ms). Electrocardiogram must be registered at rest. For any ECG assessment, if the initial ECG shows a

Trial Locations

• Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities), Basking Ridge, New Jersey, United States
• Memorial Sloan Kettering Monmouth (Limited Protocol Activities), Middletown, New Jersey, United States
• Memorial Sloan Kettering Bergen (Limited Protocol Activities), Montvale, New Jersey, United States
• Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities), Commack, New York, United States
• Memorial Sloan Kettering Westchester, Harrison, New York, United States
• Memorial Sloan Kettering Cancer Center, New York, New York, United States
• Memorial Sloan Kettering Nassau (Limited Protocol Activities), Uniondale, New York, United States

Frequently Asked Questions

Related Conditions

• Small Cell Lung Cancer
• Extensive-Stage Lung Cancer
• Lung Cancer
• Oncology
• Cancer Immunotherapy
• Maintenance Therapy
• Chemotherapy
• Targeted Therapy
• Clinical Trials
• Drug Development

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