PF-07284892 in Participants With Advanced Solid Tumors

Pfizer

Status and phase: Terminated; Phase 1

Conditions: Solid Tumor

Treatments: Drug: encorafenib; Biological: cetuximab; Drug: PF-07284892; Drug: lorlatinib; Drug: binimetinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04800822

C4481001

2022-003166-21 (EudraCT Number)

2022-502431-18-00 (Registry Identifier)

SHP2 (Other Identifier)

Details and patient eligibility

About

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 as a single agent and in combination with lorlatinib, encorafenib and cetuximab, or binimetinib and evaluate the pharmacokinetics, safety, and preliminary clinical activity of single agent and each combination therapy.

Enrollment: 53 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age ≥18 years at the time of informed consent
• Histological or cytological diagnosis of ALK-positive advanced NSCLC, CRC with BRAF V600E mutation, or RAS- mutant, NF1-mutant or BRAF class 3 mutant solid tumor. Participants with ROS-positive NSCLC are also eligible for Part 1 and 2 (Other ROS1-positive solid tumors may be considered after discussion with the sponsor).
• Documentation evidence of biomarker mutation status
• Part 3:

ALK-positive NSCLC with prior lorlatinib and no prior platinum-based chemotherapy (Cohort 1); with prior lorlatinib and prior platinum-based chemotherapy (Cohort 2); or with no prior lorlatinib (Cohort 3).

BRAF V600E mutant CRC participants resistant to BRAFi plus EGFRi (Cohort 4 ); refractory to BRAFi plus EGFRi (Cohort 5); or BRAFi plus EGFRi naïve (Cohort 6).

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

Exclusion criteria

• Brain metastasis larger than 4 cm
• Active malignancy within 3 years
• Systemic anti-cancer therapy or small molecule therapeutics within 2 weeks prior to start of study treatment. Antibody based agents within 4 weeks prior to start of study treatment. Mitomycin C or nitrosoureas within 6 weeks prior to start of study treatment.
• For participants who may get lorlatinib or encorafenib on study, history of interstitial lung disease
• 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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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53 participants in 9 patient groups

PF-07284892 monotherapy

Experimental group

Description:

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

Treatment:

Drug: PF-07284892

PF-07284892 in combination with lorlatinib (Part 2)

Experimental group

Description:

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

Treatment:

Drug: lorlatinib

Drug: PF-07284892

Expansion Phase (Cohort 1)

Experimental group

Description:

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

Treatment:

Drug: lorlatinib

Drug: PF-07284892

Expansion Phase (Cohort 2)

Experimental group

Description:

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

Treatment:

Drug: lorlatinib

Drug: PF-07284892

Expansion Phase (Cohort 3)

Experimental group

Description:

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

Treatment:

Biological: cetuximab

Drug: PF-07284892

Drug: encorafenib

Expansion Phase (Cohort 4)

Experimental group

Description:

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

Treatment:

Biological: cetuximab

Drug: PF-07284892

Drug: encorafenib

Expansion Phase (Cohort 5)

Experimental group

Description:

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)

Treatment:

Drug: binimetinib

Drug: PF-07284892

PF-07284892 in combination with encorafenib and cetuximab (Part 2)

Experimental group

Description:

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

Treatment:

Biological: cetuximab

Drug: PF-07284892

Drug: encorafenib

PF-07284892 in combination with binimetinib (Part 2)

Experimental group

Description:

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

Treatment:

Drug: binimetinib

Drug: PF-07284892