PF-07284892 Combination Therapy for Solid Tumors

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

53 Participants Needed

Trial Summary

What is the purpose of this trial?

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. It targets patients who may not have responded well to other treatments. The goal is to understand how the drug works in the body and its potential benefits.

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.

What data supports the effectiveness of the drug PF-07284892 in combination therapy for solid tumors?

The research highlights that combining cancer drugs, like PD-1 checkpoint inhibitors, can potentially improve outcomes by increasing tumor-cell killing. This suggests that combination therapies, such as those involving PF-07284892, might be more effective than using a single drug alone. ^{1 2 3 4 5}

What safety data exists for PF-07284892 or similar treatments in humans?

Preliminary results from ongoing trials of lenvatinib plus pembrolizumab, a similar combination therapy for solid tumors, show a manageable safety profile, indicating it is generally safe for humans. ^{6 7 8 9 10}

What makes the drug PF-07284892 unique for treating solid tumors?

PF-07284892 is unique because it is part of a combination therapy that likely involves immune checkpoint inhibitors, which work by helping the immune system recognize and attack cancer cells more effectively. This approach aims to improve treatment response and reduce side effects compared to traditional therapies like chemotherapy or radiation. ^{3 11 12 13 14}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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.

I am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

SynergyFinder Plus: Toward Better Interpretation and Annotation of Drug Combination Screening Datasets. [2023]

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

Assessment of Clinical Activity of PD-1 Checkpoint Inhibitor Combination Therapies Reported in Clinical Trials. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitor combinations in solid tumors: opportunities and challenges. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

FOLFIRINOX is a cost-effective combination chemotherapy in first-line for advanced pancreatic Cancer. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Systematic review of combinations of targeted or immunotherapy in advanced solid tumors. [2022]

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

Continuous-infusion cisplatin, 5-fluorouracil, and leucovorin for advanced non-small cell lung cancer. [2019]

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

The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. [2021]

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

A phase I study of PF-04449913, an oral hedgehog inhibitor, in patients with advanced solid tumors. [2019]

9. England pubmed.ncbi.nlm.nih.gov

A phase II trial of tegafur-uracil plus leucovorin (LV) in the treatment of advanced biliary tract carcinomas. [2019]

10. New Zealand 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. [2022]

11. Japan pubmed.ncbi.nlm.nih.gov

[Antitumor effects of 5'-deoxy-5-fluorouridine (5'-DFUR) against various murine tumors in combination with recombinant interferon alpha or cytostatics]. [2015]

12. England pubmed.ncbi.nlm.nih.gov

Predicting tumor cell line response to drug pairs with deep learning. [2020]

13. England pubmed.ncbi.nlm.nih.gov

Effective drug combinations in breast, colon and pancreatic cancer cells. [2022]

14. Netherlands pubmed.ncbi.nlm.nih.gov

The application of prodrug-based nano-drug delivery strategy in cancer combination therapy. [2017]