PF-06821497 for Small Cell Lung Cancer

Recruiting at106 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Pfizer

Must be taking: Abiraterone, Enzalutamide

Must not be taking: CYP3A4/5 inducers, inhibitors

Disqualifiers: Hypertension, Hypersensitivity, Gastrointestinal disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called PF-06821497 to see if it can help adults with certain hard-to-treat cancers. The drug is taken by mouth and is being studied alone or with other treatments to check its safety and effectiveness in stopping cancer growth.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use certain drugs that strongly affect liver enzymes (CYP3A4/5 inducers or inhibitors) within 10 days before starting the trial.

What makes the drug PF-06821497 unique for small cell lung cancer?

PF-06821497, also known as Mevrometostat, is a novel treatment option for small cell lung cancer, which is distinct from existing therapies like topotecan, the only FDA-approved second-line treatment. While traditional treatments focus on chemotherapy, PF-06821497 may offer a new mechanism of action, potentially targeting cancer cells differently, although specific details about its unique properties compared to other treatments are not provided in the available research. ^{1 2 3 4 5}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for adults with advanced lung cancer, prostate cancer resistant to hormone therapy, or follicular lymphoma. Participants must have a confirmed diagnosis, adequate organ function, and an ECOG Performance Status of 0 or 1 (fully active or restricted in physically strenuous activity but ambulatory). They should not be using certain foods/drugs that affect the study medication.

Inclusion Criteria

My cancer is advanced or has spread, and it's one of the specified types in the study.

My prostate cancer is resistant to hormonal therapy.

Patients with signs of disease on imaging tests.

Exclusion Criteria

Your heart's QTcF interval is longer than 480 milliseconds when measured during screening.

I have a history of serious stomach or bowel problems.

I am not using, nor do I need, any substances that could affect the trial medication.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive mevrometostat at escalating dose levels to determine the maximum tolerated dose (MTD)

Up to 90 days

Regular visits for dose adjustments and monitoring

Dose Expansion

Participants receive mevrometostat at the recommended phase 2 dose (RP2D) in combination with standard of care (SOC) to assess efficacy

Approximately 2 years

Baseline and every 21 days through study completion

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 2 years

Treatment Details

Interventions

• PF-06821497 (BCL-2 Inhibitor)

Trial Overview PF-06821497 is being tested in this Phase 1 trial to find out the best dose and its safety for treating relapsed/refractory small cell lung cancer (SCLC), castration-resistant prostate cancer (CRPC), and follicular lymphoma (FL). The study will gradually increase doses for new patients based on how earlier participants respond.

Participant Groups

Group I: Japan Cohort Experimental Treatment 1 Intervention

Participants with CRPC will receive mevrometostat at one or two doses

Group II: Dose Expansion (Part 2C) Experimental Treatment 2 Interventions

Participants with mCRPC will receive mevrometostat at a different dose/dosing regimen than that of Part 2B in combination with SOC

Group III: Dose Expansion (Part 2B) Experimental Treatment 2 Interventions

Participants with CRPC will receive mevrometostat in combination with SOC or SOC alone.

Group IV: Dose Escalation (Part 2A) Experimental Treatment 2 Interventions

Participants with mCRPC and SCLC will receive mevrometostat at escalating dose levels in combination with SOC.

Group V: Dose Escalation (Part 1C) Experimental Treatment 1 Intervention

Participants with mCRPC will receive PF-06821497 at escalating dose levels.

Group VI: Dose Escalation (Part 1B) Experimental Treatment 1 Intervention

Participants with FL will receive mevrometostat at escalating dose levels

Group VII: Dose Escalation (Part 1A) Experimental Treatment 1 Intervention

Participants with SCLC, CRPC and FL will receive mevrometostat at escalating dose levels

Group VIII: China cohort Experimental Treatment 1 Intervention

Participants will receive mevrometostat at one or two doses

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

Topotecan is currently the only FDA-approved second-line treatment for small-cell lung cancer, which is crucial since most patients relapse after initial therapy despite a high response rate of up to 90%.

While other agents like vinorelbine and irinotecan have shown modest efficacy, recent research has focused on optimizing topotecan dosing and exploring combination therapies, balancing increased activity with the need to manage toxicity and maintain quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-line treatment of small-cell lung cancer. MacCallum, C., Gillenwater, HH.[2019]

In a phase III study involving 144 non-progressing patients with extensive small-cell lung cancer, the addition of 3 months of oral etoposide after initial treatment significantly improved progression-free survival (PFS) from 6.5 months to 8.23 months.

While there was a trend towards improved overall survival with oral etoposide (12.2 months compared to 11.2 months), the results were not statistically significant, indicating potential benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance daily oral etoposide versus no further therapy following induction chemotherapy with etoposide plus ifosfamide plus cisplatin in extensive small-cell lung cancer: a Hoosier Oncology Group randomized study. Hanna, NH., Sandier, AB., Loehrer, PJ., et al.[2020]

In a study involving 87 patients with extensive small-cell lung cancer, temsirolimus did not significantly improve progression-free survival (PFS) compared to baseline, with median PFS of only 2.2 months overall.

While 42% of patients experienced grade 3 toxicities, including thrombocytopenia and fatigue, there were no lethal toxicities reported, indicating that temsirolimus was relatively safe despite its limited efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, phase II trial of two dose levels of temsirolimus (CCI-779) in patients with extensive-stage small-cell lung cancer who have responding or stable disease after induction chemotherapy: a trial of the Eastern Cooperative Oncology Group (E1500). Pandya, KJ., Dahlberg, S., Hidalgo, M., et al.[2018]

In a study of 120 patients with localized small cell lung cancer (SCLC), the VIP chemotherapy regimen (etoposide, ifosfamide, and cisplatin) showed a higher complete response rate (43.1%) compared to the EP regimen (25.0%), indicating superior efficacy for VIP as a first-line treatment.

The response rate for the VIP regimen was 89.6%, and it also proved effective as salvage therapy for patients who progressed after EP treatment, achieving a total response rate of 52.2% in that group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic efficacy of chemotherapy with VIP for small cell lung cancer]. Wu, C., Qi, H., Dai, Y., et al.[2011]

Current standard treatment for advanced non-small-cell lung cancer involves doublet chemotherapy, which has shown 1-year survival rates of approximately 35% and 2-year survival rates of about 15%.

Preliminary studies indicate that triplet therapy may enhance survival rates compared to double therapy, with toxicity rates being low enough to support the development of these three-drug combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triplet combination chemotherapy and targeted therapy regimens. Bunn, PA.[2005]

References

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

Second-line treatment of small-cell lung cancer. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Maintenance daily oral etoposide versus no further therapy following induction chemotherapy with etoposide plus ifosfamide plus cisplatin in extensive small-cell lung cancer: a Hoosier Oncology Group randomized study. [2020]

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

A randomized, phase II trial of two dose levels of temsirolimus (CCI-779) in patients with extensive-stage small-cell lung cancer who have responding or stable disease after induction chemotherapy: a trial of the Eastern Cooperative Oncology Group (E1500). [2018]

4. China pubmed.ncbi.nlm.nih.gov

[Therapeutic efficacy of chemotherapy with VIP for small cell lung cancer]. [2011]

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

Triplet combination chemotherapy and targeted therapy regimens. [2005]