PF-07284892 in Participants With Advanced Solid Tumors
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT04800822 |
Recruitment Status :
Active, not recruiting
First Posted : March 16, 2021
Last Update Posted : April 30, 2024
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Condition or disease | Intervention/treatment | Phase |
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Solid Tumor | Drug: PF-07284892 Drug: lorlatinib Drug: binimetinib Biological: cetuximab Drug: encorafenib | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 53 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A PHASE 1, OPEN-LABEL, MULTI-CENTER, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PRELIMINARY EVIDENCE OF ANTI-TUMOR ACTIVITY OF PF-07284892 (ARRY-558) AS A SINGLE AGENT AND IN COMBINATION THERAPY IN PARTICIPANTS WITH ADVANCED SOLID TUMORS |
Actual Study Start Date : | March 17, 2021 |
Estimated Primary Completion Date : | June 18, 2024 |
Estimated Study Completion Date : | November 29, 2025 |
Arm | Intervention/treatment |
---|---|
Experimental: PF-07284892 monotherapy
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
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Drug: PF-07284892
PF-07284892
Other Name: ARRY-558 |
Experimental: PF-07284892 in combination with lorlatinib (Part 2)
Combination dose escalation of PF-07284892 in combination with lorlatinib in participants with ALK- or ROS1-positive NSCLC
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Drug: PF-07284892
PF-07284892
Other Name: ARRY-558 Drug: lorlatinib lorlatinib
Other Name: Lorbrena; PF-06463922, Lorviqua |
Experimental: Expansion Phase (Cohort 1)
PF-07284892 + lorlatinib in participants with ALK+ NSCLC with prior lorlatinib
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Drug: PF-07284892
PF-07284892
Other Name: ARRY-558 Drug: lorlatinib lorlatinib
Other Name: Lorbrena; PF-06463922, Lorviqua |
Experimental: Expansion Phase (Cohort 2)
PF-07284892 + lorlatinib in participants with ALK+ NSCLC with no prior lorlatinib
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Drug: PF-07284892
PF-07284892
Other Name: ARRY-558 Drug: lorlatinib lorlatinib
Other Name: Lorbrena; PF-06463922, Lorviqua |
Experimental: Expansion Phase (Cohort 3)
PF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC with prior BRAF inhibitor (BRAFi) plus epidermal growth factor receptor inhibitor (EGFRi)
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Drug: PF-07284892
PF-07284892
Other Name: ARRY-558 Biological: cetuximab cetuximab
Other Name: Erbitux Drug: encorafenib encorafenib
Other Name: Braftovi, PF-07263896, LGX818 |
Experimental: Expansion Phase (Cohort 4)
PF-07284892 + encorafenib + cetuximab in participants with BRAF V600E mutant CRC with no prior BRAFi plus EGFRi
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Drug: PF-07284892
PF-07284892
Other Name: ARRY-558 Biological: cetuximab cetuximab
Other Name: Erbitux Drug: encorafenib encorafenib
Other Name: Braftovi, PF-07263896, LGX818 |
Experimental: Expansion Phase (Cohort 5)
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)
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Drug: PF-07284892
PF-07284892
Other Name: ARRY-558 Drug: binimetinib binimetinib
Other Name: Mektovi, PF-06811462, MEK162 |
Experimental: PF-07284892 in combination with encorafenib and cetuximab (Part 2)
Combination dose escalation of PF-07284892 in combination with encorafenib and cetuximab in participants with BRAF V600E mutant CRC
|
Drug: PF-07284892
PF-07284892
Other Name: ARRY-558 Biological: cetuximab cetuximab
Other Name: Erbitux Drug: encorafenib encorafenib
Other Name: Braftovi, PF-07263896, LGX818 |
Experimental: PF-07284892 in combination with binimetinib (Part 2)
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
|
Drug: PF-07284892
PF-07284892
Other Name: ARRY-558 Drug: binimetinib binimetinib
Other Name: Mektovi, PF-06811462, MEK162 |
- Part 1 and Part 2- Number of participants with dose limiting toxicities (DLTs) [ Time Frame: Cycle 1 (21 days) ]DLTs will be evaluated during the first cycle (21 days) as both a single agent or in combination with lorlatinib, encorafenib + cetuximab, or binimetinib. The number of DLTs will be used to determine the maximum tolerated dose (MTD)/recommended dose for further study
- Part 1 and Part 2- Number of participants with treatment-emergent adverse events (AEs) [ Time Frame: Baseline up to 30 days after last dose of study medication ]AEs as characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy
- Part 1 and Part 2 - Number of participants with clinically significant change from baseline in laboratory abnormalities [ Time Frame: Baseline up to 30 days after last dose of study treatment ]Laboratory abnormalities as characterized by type, frequency, severity, and timing
- Part 1 and Part 2 - Number of dose interruptions, dose modifications, and discontinuations due to AEs [ Time Frame: Baseline up to 30 days after the last dose of study medication ]Incidence of dose interruptions, dose modifications, and discontinuations due to AEs
- Part 3- Overall response [ Time Frame: Baseline to up to 2 years ]Response will be evaluated via radiographical tumor assessments by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
- Part 1 and Part 2- Maximum plasma concentration (Cmax) of PF-07284892 and metabolite [ Time Frame: 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); Cycle 2-6 Day 1 (predose and 2 hours postdose); Cycle 7-12 Day 1 predose; end of treatment (EOT) ]single dose (Cmax) and multiple dose (assuming steady state is achieved; Css,max) pharmacokinetic (PK) parameters
- Part 1 and Part 2- Time to reach maximum plasma concentration (Tmax) of PF-07284892 and metabolite [ Time Frame: 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); Cycle 2-6 Day 1 (predose and 2 hours postdose); Cycle 7-12 Day 1 predose; EOT ]Single dose (Tmax) and multiple dose (assuming steady state is achieved; Tss,max) pharmacokinetic parameters
- 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 [ Time Frame: 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); Cycle 2-6 Day 1 (predose and 2 hours postdose); Cycle 7-12 Day 1 predose; EOT ]Single dose PK parameter
- 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 [ Time Frame: 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); Cycle 2-6 Day 1 (predose and 2 hours postdose); Cycle 7-12 Day 1 predose; EOT ]Single dose and multiple dose (assuming steady state is achieved) PK parameter
- Part 1 and Part 2- Metabolite ratio of PF-07284892 and metabolite [ Time Frame: 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); Cycle 2-6 Day 1 (predose and 2 hours postdose); Cycle 7-12 Day 1 predose; EOT ]Single dose PK parameter
- 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 [ Time Frame: 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); Cycle 2-6 Day 1 (predose and 2 hours postdose); Cycle 7-12 Day 1 predose; EOT ]Multiple dose (assuming steady state is achieved) PK parameter
- Part 1 and Part 2- Overall response [ Time Frame: Baseline to up to 2 years ]Response will be evaluated via radiographical tumor assessments by RECIST v1.1
- Part 2- Duration of Response (DOR) [ Time Frame: Baseline to up to 2 years ]Time from the first documentation of objective response to the first documentation of objective progressive disease, relapse or to death due to any cause
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04800822
Study Director: | Pfizer CT.gov Call Center | Pfizer |
Responsible Party: | Pfizer |
ClinicalTrials.gov Identifier: | NCT04800822 |
Other Study ID Numbers: |
C4481001 2022-502431-18-00 ( Registry Identifier: CTIS (EU) ) 2022-003166-21 ( EudraCT Number ) SHP2 ( Other Identifier: Alias Study Number ) |
First Posted: | March 16, 2021 Key Record Dates |
Last Update Posted: | April 30, 2024 |
Last Verified: | April 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Plan Description: | Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests. |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
colorectal cancer non-small cell lung cancer B-type Raf proto-oncogene (BRAF) mutation Ras mutation |
anaplastic lymphoma kinase (ALK)-positive neurofibromatosis type 1 (NF1) ROS1 |
Neoplasms Cetuximab Antineoplastic Agents, Immunological Antineoplastic Agents |