What side effects are associated with this type of intervention?

Common treatments for solid tumors, including chemotherapy and targeted therapies like lorlatinib, encorafenib, cetuximab, and binimetinib, often have a range of side effects. Chemotherapy can cause neutropenia, fatigue, neuropathy, and gastrointestinal issues such as nausea and diarrhea. Targeted therapies may lead to specific toxicities like hypertension, hypothyroidism, and skin reactions. For example, cetuximab can cause acneiform rash and infusion reactions, while encorafenib and binimetinib may result in skin toxicity, diarrhea, and cardiovascular effects. It is important to discuss these potential side effects with a healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of solid tumors, particularly those targeting specific molecular pathways. Lorlatinib, an ALK inhibitor, is approved for ALK-positive non-small cell lung cancer. Encorafenib, a BRAF inhibitor, is approved in combination with binimetinib, a MEK inhibitor, for BRAF V600E or V600K mutation-positive melanoma. Cetuximab, an EGFR inhibitor, is approved for metastatic colorectal cancer and head and neck cancer. These drugs target specific genetic mutations or proteins involved in tumor growth and are often used in combination to enhance therapeutic efficacy.

What other types of research exist?

Promising alternatives to PF-07284892 for solid tumors include multitargeted kinase inhibitors like regorafenib, cabozantinib, sorafenib, and lenvatinib. These agents target VEGFR and other kinases and have shown some activity in advanced cancers. Additionally, immunotherapies such as pembrolizumab and atezolizumab, often used in combination with chemotherapy, are also viable options. Clinical trials for these agents are ongoing, and they represent novel approaches for treating solid tumors.

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PF-07284892 Combination Therapy for Solid Tumors

Phase 1

Waitlist Available

Research Sponsored by Pfizer

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age ≥18 years at the time of informed consent

RAS- mutant, NF1-mutant or BRAF class 3 mutant solid tumors who have received prior SOC (Cohort 7).

Must not have

For participants who may get binimetinib on study, history or current evidence of retinal vein occlusion (RVO) or concurrent neuromuscular disorder associated with elevated creatine kinase (CK)

Brain metastasis larger than 4 cm

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline to up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include risks associated with each drug: lung issues from lorlatinib or encorafenib; vision problems like retinal vein occlusion from binimetinib; general risks of fatigue, digestive discomfort, skin reactions, and increased infection risk.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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

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I have paperwork showing the genetic changes in my cancer.

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My colorectal cancer is BRAF V600E mutant and has not responded to or has not been treated with BRAFi and EGFRi.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I have a brain tumor larger than 4 cm.

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I have never had interstitial lung disease.

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I have had cancer within the last 3 years.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline to up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline to up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Part 1 and Part 2 - Number of dose interruptions, dose modifications, and discontinuations due to AEs

Part 1 and Part 2 - Number of participants with clinically significant change from baseline in laboratory abnormalities

Part 1 and Part 2- Number of participants with dose limiting toxicities (DLTs)

+2 more

Secondary study objectives

Part 1 and Part 2- Area under the plasma concentration-time curve from 0 to 24 (AUC24) or 48 hours (AUC48) of PF-07284892 and metabolite

Part 1 and Part 2- Area under the plasma concentration-time curve from time 0 to extrapolated to infinity (AUCinf) of PF-07284892 and metabolite

Part 1 and Part 2- Area under the plasma concentration-time curve from time 0 to the last time point of quantifiable concentration (AUClast) of PF-07284892 and metabolite

+5 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

9Treatment groups

Experimental Treatment

Group I: PF-07284892 monotherapyExperimental Treatment1 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 Treatment2 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 Treatment3 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 Treatment2 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 Treatment4 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 Treatment3 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 Treatment4 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 Treatment2 Interventions

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

Group IX: Expansion Phase (Cohort 1)Experimental Treatment2 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

binimetinib

2018

Completed Phase 2

~140

encorafenib

2019

Completed Phase 2

~160

lorlatinib

2023

N/A

~550

cetuximab

2000

Completed Phase 3

~7290

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for solid tumors often involve targeted therapies that interfere with specific molecular pathways critical for tumor growth and survival. Lorlatinib targets ALK and ROS1 gene rearrangements, inhibiting tumor cell proliferation. Encorafenib inhibits the BRAF V600E mutation, which is involved in cell growth signaling pathways. Cetuximab is an antibody that targets the EGFR receptor, blocking cell proliferation and survival signals. Binimetinib inhibits MEK1 and MEK2, which are part of the MAPK/ERK pathway involved in cell division. These targeted therapies are significant for solid tumor patients as they offer more precise treatment options, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.