PF-06821497 for Small Cell Lung Cancer

Recruiting at 144 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pfizer

Must be taking: Abiraterone, Enzalutamide

Must not be taking: CYP3A4/5 inducers, inhibitors

Disqualifiers: Hypertension, Hypersensitivity, Gastrointestinal disease, others

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

Compensation: Varies

Number of Visits: 21

433 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called PF-06821497 (Mevrometostat) for individuals with specific cancers, such as small cell lung cancer and castration-resistant prostate cancer, that have recurred or not responded to previous treatments. The goal is to determine the optimal dose that is both safe and effective. The trial includes different groups to test various doses and combinations with other treatments. It may suit someone with castration-resistant prostate cancer who has tried treatments like abiraterone and whose cancer shows signs of progression. As an early-phase trial, it primarily aims to establish the right dose and assess safety. Being a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that PF-06821497 is likely to be safe for humans?

Research has shown that PF-06821497, also known as Mevrometostat, is still undergoing testing to determine its safety for people. Researchers are studying this drug for use in certain cancers, such as small cell lung cancer, prostate cancer, and follicular lymphoma. Since the treatment is in the early stages of testing, researchers are carefully monitoring its safety. These early tests focus on understanding possible side effects and how well people can tolerate different doses. Although all safety details are not yet available, this phase is crucial for identifying the best and safest way to use this treatment in the future. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for small cell lung cancer (SCLC) focus on chemotherapy and radiation. But PF-06821497 works differently. Researchers are excited about this drug because it targets specific enzymes involved in cancer cell growth and survival, potentially offering a more precise approach than traditional chemotherapy. This could mean fewer side effects and better effectiveness for patients. By disrupting the cancer cell's ability to thrive, PF-06821497 may change the game for those with SCLC.

What evidence suggests that this trial's treatments could be effective for small cell lung cancer, castration-resistant prostate cancer, and follicular lymphoma?

Research has shown that Mevrometostat, also known as PF-06821497, is under investigation in this trial for its potential to treat challenging cancers like small cell lung cancer (SCLC) and castration-resistant prostate cancer (CRPC). Participants in different trial arms will receive Mevrometostat at varying doses and combinations. Early studies suggest that Mevrometostat targets a specific process in cancer cells, potentially slowing their growth. Although detailed information from human studies remains limited, initial results are promising in controlling cancer progression. The treatment aims to help patients whose cancer has returned or resisted other treatments. However, researchers are still studying its safety and full effectiveness. ^{1 2 5 6 7}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• PF-06821497

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.

How Is the Trial Designed?

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: DDI Substudy Experimental Treatment 2 Interventions

In the assessment phase, each enrolled participant will receive a combination of mevrometostat, enzalutamide, and itraconazole based on preset schedule. In the maintenance phase, each participant will receive mevrometostat 2 times a day and enzalutamide 1 time a day.

Group IX: China cohort Experimental Treatment 1 Intervention

Participants will receive mevrometostat at one or two doses

Group X: BE Substudy Experimental Treatment 2 Interventions

In the assessment phase, each enrolled participant will receive single doses of the 2 different mevrometostat formulations in 3 periods with alternating dosing and washout between each dose. In the maintenance phase, each participant will receive mevrometostat 2 times a day and enzalutamide 1 time a day.

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

Published Research Related to This Trial

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 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]

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]

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]

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]

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Study Details | NCT03460977 | Mevrometostat Treatment ...

A Phase 1 Dose Escalation and Expanded Cohort Study Of PF-06821497 (Mevrometostat) in Adult Patients With Relapsed/Refractory Small Cell Lung Cancer (SCLC), ...

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The study aims to evaluate the safety and efficacy of Mevrometostat in treating these challenging cancer types, highlighting its potential ...

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Mevrometostat (PF-06821497) is an investigational compound. Its safety and efficacy have not been established.

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Clinical Trial: NCT03460977

This is an open label, multi center, Phase 1 dose escalation study of PF 06821497 administered orally as a single agent BID to patients with SCLC, CRPC, DLBCL ...

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488P Phase I trial of PF-06821497, a potent and selective ...

A potent and selective inhibitor of enhancer of zeste homolog 2 (EZH2), in follicular lymphoma (FL), small cell lung cancer (SCLC) and castration-resistant ...

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Mevrometostat Treatment of Relapsed/Refractory SCLC, ...

This is an open label, multi center, Phase 1 dose escalation and dose expansion study of mevrometostat (PF-06821497) administered orally BID as ...