PF-07284892 Combination Therapy for Solid Tumors

No longer recruiting at 20 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pfizer

Must not be taking: Antibody agents, Mitomycin C

Disqualifiers: Brain metastasis, Active malignancy, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, PF-07284892, for various solid tumors. Researchers aim to determine the optimal dose and assess its safety and effectiveness when used alone or with other cancer drugs, such as lorlatinib, encorafenib, cetuximab, and binimetinib. The trial seeks participants with specific genetic mutations in their tumors, including ALK-positive non-small cell lung cancer (NSCLC), BRAF V600E mutant colorectal cancer (CRC), or RAS/NF1 mutant solid tumors, who have previously tried standard treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking any systemic anti-cancer therapy or small molecule therapeutics at least 2 weeks before starting the study treatment. If you are taking antibody-based agents, you need to stop them 4 weeks before, and for Mitomycin C or nitrosoureas, you need to stop 6 weeks before.

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

Research shows that PF-07284892 is being tested alone and with other drugs like lorlatinib, encorafenib, cetuximab, and binimetinib to determine the safest dose. This treatment is in the early stages of human testing, with the primary goal of assessing tolerance and potential side effects.

For PF-07284892 and its combinations, studies have not yet provided detailed safety information. The research focuses on identifying the highest safe dose, with close monitoring for safety. While detailed safety data is limited, early studies typically observe participants' reactions to new treatments carefully.

The drugs used with PF-07284892, such as lorlatinib, encorafenib, cetuximab, and binimetinib, have been used in other treatments. For instance, encorafenib and cetuximab are approved for certain types of colorectal cancer, suggesting they may be reasonably safe when combined with PF-07284892.

Overall, while detailed safety data is not yet available, this trial is designed to closely monitor any side effects to ensure participants' safety. Participants should discuss any specific concerns with the study team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about PF-07284892 because it offers a potentially more targeted approach for treating certain types of cancer. Unlike current treatments that broadly attack cancer cells, PF-07284892 specifically targets genetic mutations such as RAS, NF1, and BRAF class 3 mutations found in solid tumors. This precision could mean fewer side effects and more effective treatment outcomes. Additionally, the combination with drugs like lorlatinib, binimetinib, encorafenib, and cetuximab aims to enhance efficacy by tackling cancer through multiple pathways simultaneously, which could be a game-changer for difficult-to-treat mutations. This multi-pronged strategy is what sets these investigational treatments apart from existing options.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research has shown that using the drugs encorafenib and cetuximab together can extend the lives of patients with a specific type of colorectal cancer. Studies found that this combination reduces the risk of death by half compared to standard treatments. In this trial, PF-07284892 is being studied alongside encorafenib and cetuximab for participants with BRAF V600E mutant colorectal cancer.

Additionally, lorlatinib is being tested with PF-07284892 for participants with ALK-positive non-small cell lung cancer (NSCLC), providing a strong and lasting effect. Binimetinib, also tested with PF-07284892, targets specific gene changes in solid tumors to inhibit cancer cell growth. PF-07284892 is a new drug under investigation to assess its effectiveness with these treatments by targeting different gene changes that cause cancer. Early research in this trial aims to determine the optimal dose and evaluate its safety and effectiveness. ^{1 3 6 7 8}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

Adults with certain advanced solid tumors, including lung cancer (ALK-positive NSCLC), colorectal cancer with BRAF V600E mutation, or other specific mutations. Participants must have tried standard treatments and be free from large brain metastases and recent anti-cancer therapies.

Inclusion Criteria

My cancer is ALK-positive NSCLC, CRC with BRAF V600E, or has specific mutations.

My NSCLC is ALK-positive. I may or may not have had lorlatinib or platinum-based chemotherapy.

My tumor has specific genetic mutations and I've had standard treatment.

Exclusion Criteria

I do not have a history of retinal vein occlusion or muscle disorders with high CK levels.

I haven't taken any cancer drugs or had antibody treatments in the weeks before starting this study.

I have a brain tumor larger than 4 cm.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of PF-07284892 as a single agent or in combination to determine the maximum tolerated dose

21 days per cycle

Cycle 1 Day 1 (predose, 1, 2, 4, 6, 8 hours postdose); Cycle 1 Day 18 (predose, 1, 2, 4, 6, 8, 24, and 48 hours postdose)

Dose Expansion

Participants receive the recommended dose of PF-07284892 in combination with other therapies to evaluate safety and preliminary clinical activity

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days after last dose

What Are the Treatments Tested in This Trial?

Interventions

• PF-07284892

Trial Overview PF-07284892 is being tested alone and in combination with lorlatinib, encorafenib plus cetuximab, or binimetinib to find the safest dose for future studies. The trial will also assess how the body processes these drugs and their preliminary effects on tumors.

How Is the Trial Designed?

Group I: PF-07284892 monotherapy Experimental Treatment 1 Intervention

Monotherapy dose escalation of PF-07284892 in participants with ALK- or ROS1-positive non-small cell lung cancer (NSCLC), B-type Raf proto-oncogene V600E mutation colorectal cancer (CRC), or RAS- mutant, NF1-mutant or BRAF class 3-mutant solid tumors

Group II: PF-07284892 in combination with lorlatinib (Part 2) Experimental Treatment 2 Interventions

Combination dose escalation of PF-07284892 in combination with lorlatinib in participants with ALK- or ROS1-positive NSCLC

Group III: PF-07284892 in combination with encorafenib and cetuximab (Part 2) Experimental Treatment 3 Interventions

Combination dose escalation of PF-07284892 in combination with encorafenib and cetuximab in participants with BRAF V600E mutant CRC

Group IV: PF-07284892 in combination with binimetinib (Part 2) Experimental Treatment 2 Interventions

Combination dose escalation of PF-07284892 in combination with binimetinib in participants with Ras-mutant, NF-1 mutant or BRAF class 3 -mutant solid tumors

Group V: Expansion Phase (Cohort 5) Experimental Treatment 4 Interventions

PF-07284892 + binimetinib in participants with RAS- mutant, NF1-mutant or BRAF class 3 mutant solid tumors who have received prior standard of care (SOC)

Group VI: Expansion Phase (Cohort 4) Experimental Treatment 3 Interventions

PF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC with no prior BRAFi plus EGFRi

Group VII: Expansion Phase (Cohort 3) Experimental Treatment 4 Interventions

PF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC with prior BRAF inhibitor (BRAFi) plus epidermal growth factor receptor inhibitor (EGFRi)

Group VIII: Expansion Phase (Cohort 2) Experimental Treatment 2 Interventions

PF-07284892 + lorlatinib in participants with ALK+ NSCLC with no prior lorlatinib

Group IX: Expansion Phase (Cohort 1) Experimental Treatment 2 Interventions

PF-07284892 + lorlatinib in participants with ALK+ NSCLC with prior lorlatinib

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 of 16 patients with advanced biliary tract carcinoma, oral tegafur-uracil combined with leucovorin was found to be well tolerated, with only two patients experiencing significant toxicities (grade III/IV).

Despite its safety profile, the treatment showed no objective responses, with the majority of patients experiencing disease progression, indicating that it is ineffective for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of tegafur-uracil plus leucovorin (LV) in the treatment of advanced biliary tract carcinomas. Chen, JS., Yang, TS., Lin, YC., et al.[2019]

The maximum tolerated dose (MTD) of PF-04449913 was determined to be 320 mg once daily, with the drug generally well tolerated at doses between 80 to 320 mg, and only mild to moderate side effects reported.

PF-04449913 effectively modulated hedgehog signaling in patients, leading to stable disease in 34.8% of participants, indicating potential for further evaluation in treating advanced solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of PF-04449913, an oral hedgehog inhibitor, in patients with advanced solid tumors. Wagner, AJ., Messersmith, WA., Shaik, MN., et al.[2019]

In a real-world study involving 196 patients with metastatic colorectal cancer, the combination of bevacizumab and chemotherapy resulted in a median progression-free survival of 8.22 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally safe, with the most common adverse event being hypertension (28%), and only 15.2% of patients experiencing severe (Grade 3/4) adverse events, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Non-Interventional Multicenter Study of First-Line Bevacizumab in Combination with Chemotherapy in Patients with Metastatic Colorectal Cancer in Lebanon. Temraz, S., Nasr, F., Kattan, J., et al.[2022]

Immune checkpoint inhibitors like CTLA-4 and PD-1 have significantly changed the treatment landscape for solid tumors, including melanoma and lung cancer, by enhancing the body's immune response against cancer cells.

Combining checkpoint inhibitors with other therapies (like chemotherapy or cancer vaccines) aims to improve treatment effectiveness while reducing side effects, highlighting the need for reliable biomarkers to identify patients who will benefit the most.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitor combinations in solid tumors: opportunities and challenges. Kyi, C., Postow, MA.[2021]

The combination of lenvatinib, a multikinase inhibitor, and pembrolizumab, a PD-1 inhibitor, shows promising antitumor activity and durable responses in various solid tumors, as indicated by preliminary results from the LEAP clinical trial program.

This combination therapy has a manageable safety profile, suggesting it could be a valuable new treatment option for solid cancers that currently have limited therapeutic alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. Taylor, MH., Schmidt, EV., Dutcus, C., et al.[2021]

A systematic review of 32 clinical trials on novel-novel combination therapies for advanced solid tumors revealed that many trials (72%) lacked strong preclinical evidence supporting their combinations, highlighting a gap in the biological rationale for these therapies.

Most trials (69%) were conducted in biomarker-unselected populations, suggesting a need for better patient selection based on predictive biomarkers to enhance the efficacy and relevance of combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of combinations of targeted or immunotherapy in advanced solid tumors. Tan, AC., Bagley, SJ., Wen, PY., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04800822

PF-07284892 in Participants With Advanced Solid Tumors The purpose of this first-in-patient, open label study is to determine the maximum tolerated dose and/or recommended dose for further study of PF-07284892 ...

2. withpower.com withpower.com/trial/phase-1-neoplasms-2-2021-63a10

PF-07284892 Combination Therapy for Solid Tumors This trial is testing a new drug called PF-07284892 alone and with other drugs to find the best dose and see how safe and effective it is.

3. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04800822/

Clinical Trial: NCT04800822 PF-07284892 monotherapy, Experimental, Monotherapy dose escalation of PF-07284892 in participants with ALK- or ROS1-positive non-small cell lung ...

4. data.niaid.nih.gov data.niaid.nih.gov/resources?id=2370923

PF-07284892 in Participants With Advanced Solid Tumors The purpose of this first-in-patient, open label study is to determine the maximum tolerated dose and/or recommended dose for further study of PF-07284892 ...

5. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT04800822?keyword=%22NF1%22

PF-07284892 in Participants With Advanced Solid Tumors The purpose of this first-in-patient, open label study is to determine the maximum tolerated dose and/or recommended dose for further study of PF-07284892 ...

6. mayo.edu mayo.edu/research/clinical-trials/cls-20538910

PF-07284892 in Participants With Advanced Solid Tumors The purpose of this study is to determine the maximum tolerated dose and/or recommended dose for further study of PF-07284892 as a single agent and in ...

7. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.3020

A first-in-human, phase 1 study of the SHP2 inhibitor PF- ... Methods: Eligible pts with advanced solid tumors were enrolled into escalating dose cohorts of PF-07284892 monotherapy. ... solid tumors with BRAF ...

8. clinconnect.io clinconnect.io/trials/NCT04800822

PF-07284892 in Participants With Advanced Solid Tumors The purpose of this first-in-patient, open label study is to determine the maximum tolerated dose and/or recommended dose for further study of PF-07284892 ...