Valemetostat + Atezolizumab for Small Cell Lung Cancer

Recruiting at 6 trial locations

Overseen By Alissa Cooper, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Platinum doublet, Atezolizumab

Must not be taking: CYP3A inducers

Disqualifiers: Uncontrolled diseases, CNS metastases, 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: 10

24 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you should avoid certain herbs and fruits like St. John's wort and grapefruit, and you cannot take medications that strongly affect CYP3A enzymes within 14 days of starting the trial.

What data supports the effectiveness of the drug combination Valemetostat + Atezolizumab for treating small cell lung cancer?

Research shows that adding atezolizumab to chemotherapy improves survival in patients with extensive-stage small cell lung cancer compared to chemotherapy alone, suggesting it could be a promising treatment option. ^{1 2 3 4 5}

Is the combination of Valemetostat and Atezolizumab safe for humans?

Atezolizumab has been studied in patients with non-small cell lung cancer and is generally considered to have manageable safety, with serious treatment-related side effects occurring in a small percentage of patients. No new safety concerns were identified in these studies. ^{4 5 6 7 8}

How is the drug combination of Valemetostat and Atezolizumab unique for treating small cell lung cancer?

The combination of Valemetostat and Atezolizumab is unique because it pairs a novel drug, Valemetostat, with Atezolizumab, an immunotherapy that blocks PD-L1 (a protein that helps cancer cells evade the immune system), potentially offering a new approach to enhance the immune response against small cell lung cancer. ^{1 3 4 5 9}

Research Team

Charles Rudin, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with newly diagnosed extensive-stage small cell lung cancer who've had a good response to initial chemo and immunotherapy. They must be able to follow the study plan, have decent kidney and liver function, no major recent surgeries or uncontrolled diseases like heart problems or infections, not pregnant or breastfeeding, and without other cancers in the last 3 years.

Inclusion Criteria

Signed informed consent form (ICF)

Ability to comply with the study protocol as per the investigator's judgment

I am fully active or can carry out light work.

Exclusion Criteria

I haven't had major surgery or significant injury in the last 4 weeks.

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 prolonged QTc, then two additional ECGs will be obtained, resulting in three specimens taken after a space of 1 minute, and the mean of the 3 ECGs will be used to determine eligibility and for grading of TRAEs, Myocardial infarction within 6 months prior to screening, Uncontrolled angina pectoris within 6 months prior to screening, New York Heart Association (NYHA) Class 3 or 4 congestive heart failure, Uncontrolled hypertension (resting systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg), Have a known hypersensitivity to any of the components of or known hypersensitivity to either the study drug itself or any of the inactive ingredients in the study drug product, Known liver cirrhosis, Uncontrolled active infection requiring IV antibiotic, antiviral, or anti-fungal medications within 14 days prior to initiation of study treatment. Infections controlled on concurrent anti-microbial agents and anti-microbial prophylaxis per institutional guidelines are acceptable, Congenital or acquired immunodeficiency, including patients with known history or infection with human immunodeficiency virus (HIV). HIV-positive patients who are taking anti-retroviral therapy are still ineligible due to potential PK interactions with valemetostat, Active tuberculosis, Active hepatitis B virus (HBV) infection (chronic or acute), defined as having a positive hepatitis B surface antigen (HBsAg) test followed by a positive HBV RNA test within 28 days prior to the first dose of study drug. Hepatitis B testing (HBV surface antigen and core antibody) is required only if not done previously. Patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test at screening, are eligible for the study, Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test followed by a positive HCV RNA test within 28 days prior to the first dose of study drug. Hepatitis C testing (HCV antibody) is required only if not done previously. The HCV RNA test will be performed only for patients who have a positive HCV antibody test, Prior malignancy, active within the previous 3 years, except for locally curable cancer that is currently considered as cured or successfully resected, such as basal or squamous cell carcinoma, superficial bladder cancer, gastric cancer or carcinoma in situ of the prostate, cervix, or breast, Female patients who have a positive serum pregnancy test during screening or a positive urine pregnancy test on Day 1 before first dose of study drug, Female patients who are lactating and/or plan to breastfeed during the study treatment or at any point leading up to and including 6 months after the last study drug dose

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding

Researchers test different doses of valemetostat to find the highest dose that causes few or mild side effects

12 weeks

4 visits (in-person)

Expansion

Researchers test the determined dose in a new group of participants to learn more about the safety and effectiveness of the study treatment

24 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Atezolizumab
• Valemetostat

Trial Overview The trial is testing different doses of Valemetostat combined with Atezolizumab to find the highest dose that's safe with few mild side effects for treating extensive-stage small cell lung cancer. After finding this dose, it will be tested further for safety and effectiveness.

Participant Groups

Group I: Valemetostat in Combination With Atezolizumab Experimental Treatment 2 Interventions

This is a single institution phase 1 study to assess the safety of valemetostat when used in combination with atezolizumab for the treatment of extensive-stage SCLC patients. We will begin enrollment at a valemetostat dose of 150 mg once daily (dose level 1), with atezolizumab given per standard of care 1680 mg intravenously every four weeks. The study will have two phases, a dose finding phase and an expansion phase.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Daiichi Sankyo

Industry 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

Findings from Research

In a study of 99 previously untreated patients with extensive disease small cell lung cancer (ED-SCLC), adding atezolizumab to the standard carboplatin and etoposide regimen significantly improved overall survival, extending it to 20.8 months compared to 12.1 months for those receiving carboplatin and etoposide alone.

While there was no significant difference in progression-free survival between the two treatment groups, certain subgroups (such as older patients, males, and those with better health status) showed particularly enhanced survival benefits from the addition of atezolizumab, indicating its potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. Kubo, S., Kobayashi, N., Matsumoto, H., et al.[2023]

The combination of atezolizumab, a PD-L1 inhibitor, with platinum-based chemotherapy significantly improves overall survival in patients with extensive-stage small cell lung cancer compared to chemotherapy alone.

This research suggests that this combination therapy could become a new first-line treatment option for patients suffering from this aggressive form of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study: Atezolizumab Improves Survival in SCLC. [2019]

In a phase 1 study involving 17 patients with relapsed or refractory small-cell lung cancer (SCLC), atezolizumab was generally well tolerated, with 64.7% experiencing any-grade treatment-related adverse events, the most common being fatigue.

Atezolizumab showed some antitumor activity, with a partial response in 5.9% of patients and a median overall survival of 5.9 months, suggesting potential benefits for patients with high T-effector gene signature and PD-L1 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer. Chiang, AC., Sequist, LVD., Gilbert, J., et al.[2021]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

In a study of 47 patients with transformed small-cell lung cancer (T-SCLC), combining the PD-L1 inhibitor atezolizumab with chemotherapy resulted in a high objective response rate of 73% and significantly improved overall survival (20.2 months) compared to those who did not receive immunotherapy (7.9 months).

The combination therapy was well tolerated, showing a safety profile consistent with previous studies, suggesting it could be a promising treatment option for T-SCLC patients, particularly those with positive PD-L1 status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A potential treatment option for transformed small-cell lung cancer on PD-L1 inhibitor-based combination therapy improved survival. Zhang, CY., Sun, H., Su, JW., et al.[2023]

Atezolizumab therapy significantly improves overall survival (median OS of 11.2 months) in patients with previously treated advanced non-small cell lung cancer (NSCLC), demonstrating its efficacy in a diverse patient population.

The treatment has a manageable safety profile, with serious adverse events occurring in only 8.0% of patients and no new safety signals identified, indicating it is a viable option for patients often excluded from clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final results from TAIL: updated long-term efficacy of atezolizumab in a diverse population of patients with previously treated advanced non-small cell lung cancer. Ardizzoni, A., Azevedo, S., Rubio-Viqueira, B., et al.[2022]

Atezolizumab treatment in 615 patients with previously treated advanced non-small cell lung cancer showed a median overall survival of 11.1 months and a median progression-free survival of 2.7 months, indicating its efficacy in this population.

The safety profile was manageable, with treatment-related serious adverse events occurring in 7.8% of patients and immune-related adverse events in 8.3%, confirming that atezolizumab can be safely administered even to patients with severe renal impairment and other challenging conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary results from TAIL: a global single-arm safety study of atezolizumab monotherapy in a diverse population of patients with previously treated advanced non-small cell lung cancer. Ardizzoni, A., Azevedo, S., Rubio-Viqueira, B., et al.[2021]

In a phase 2 trial involving 287 patients with previously treated advanced non-small-cell lung cancer (NSCLC), atezolizumab significantly improved overall survival (12.6 months) compared to docetaxel (9.7 months), with a hazard ratio of 0.73, indicating a 27% reduction in the risk of death.

The efficacy of atezolizumab was found to correlate with PD-L1 expression levels on tumor cells and immune cells, suggesting that higher PD-L1 expression may predict better outcomes with this treatment, while atezolizumab also demonstrated a better safety profile with fewer severe adverse events compared to docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Fehrenbacher, L., Spira, A., Ballinger, M., et al.[2022]

The FDA approved atezolizumab, a PD-L1 inhibitor, in combination with carboplatin and etoposide as a first-line treatment for small cell lung cancer, highlighting its role in enhancing therapy options.

This approval was supported by the phase III IMpower133 trial, which demonstrated that the addition of atezolizumab significantly improved both overall survival and progression-free survival in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Atezolizumab OK'd for SCLC. [2020]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. [2023]

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

Study: Atezolizumab Improves Survival in SCLC. [2019]

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

Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer. [2021]

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

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. [2022]

5. Ireland pubmed.ncbi.nlm.nih.gov

A potential treatment option for transformed small-cell lung cancer on PD-L1 inhibitor-based combination therapy improved survival. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Final results from TAIL: updated long-term efficacy of atezolizumab in a diverse population of patients with previously treated advanced non-small cell lung cancer. [2022]

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

Primary results from TAIL: a global single-arm safety study of atezolizumab monotherapy in a diverse population of patients with previously treated advanced non-small cell lung cancer. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. [2022]

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

First-Line Atezolizumab OK'd for SCLC. [2020]