A PHASE I OPEN-LABEL, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND ANTI TUMOR ACTIVITY OF PF-07799933 (ARRY-440) AS A SINGLE AGENT AND IN COMBINATION THERAPY IN PARTICIPANTS 16 YEARS AND OLDER WITH ADVANCED SOLID TUMORS WITH BRAF ALTERATIONS

Study Identifier:
C4761001
CT.gov Identifier:
NCT05355701
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
N/A
Study Contact Information:
N/A
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Study Summary

To Evaluate efficacy ,safety of PHARMACOKINETICS, AND ANTI TUMOR ACTIVITY OF PF-07799933 (ARRY-440) AS A SINGLE AGENT AND IN COMBINATION THERAPY IN PARTICIPANTS 16 YEARS AND OLDER WITH ADVANCED SOLID TUMORS WITH BRAF ALTERATIONS

To study the effect of PF-07799933 as monotherapy or in combination with binimetinib or cetuximab in participants with BRAF-altered advanced solid tumors.

To investigate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and potential clinical benefits of PF-07799933 administered as a single agent and in combination in participants with BRAF Class I, II and III mutated solid tumors with or without brain involvement.

The primary objective of Part 1 is to determine monotherapy MTD/RDE of PF-07799933.

The primary objective of Part 3 is efficacy in defined cohorts (total ~120 participants): Cohort 1-2: BRAF V600 mutant melanoma; Cohort 3: BRAF Class II altered melanoma; Cohorts 4-5: BRAF V600 and Class II altered CRC; Cohort 6: other BRAF V600, Class II/III altered solid tumor not qualifying for Cohorts 1-5.

To investigate PF-07799933 in pts with refractory BRAF-mutant solid tumors using a novel first-in-patient phase 1 design that enabled flexible, rapid dose escalation based on safety and pharmacokinetics (PK) assessments

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Melanoma
  • Non-Small Cell Lung Cancer
  • Thyroid
  • Glioma
  • Bowel (Colorectal)
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    16+ years
    Study Drug
  • Drug: Experimental: Monotherapy dose escalation (Part 1) Participants will receive PF-07799933 Drug: PF-07799933 Tablet Experimental: Combination dose escalation (Part 2) Participants will receive PF-07799933 in combination with binimetinib or cetuximab Drug: PF-07799933 Tablet Other Name: ARRY-440 Drug: binimetinib Tablet Other Name: Mektovi, PF-06811462, MEK162 Biological: cetuximab Injection for intravenous use Other Name: Erbitux Experimental: Dose expansion (Part 3) - Tumor and mutation specific Cohort 1 Participants will receive PF-07799933 Drug: PF-07799933 Tablet Experimental: Dose expansion (Part 3) - Tumor and mutation specific Cohort 2 Participants will receive PF-07799933 Drug: PF-07799933 Tablet Other Name: ARRY-440 Drug: binimetinib Tablet Other Name: Mektovi, PF-06811462, MEK162
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    Inclusion criteria
    • Diagnosis of advanced/metastatic solid tumor including primary brain tumor.Qualifying BRAF alteration (V600 or non-V600 Class II/Class III BRAF alteration), in tumor tissue and/or blood (ie circulating tumor deoxyribonucleic acid [DNA], or ctDNA).Disease progressed during/following last prior treatment and no satisfactory alternative treatment options (Part 1, Part 2 (doublet), and Part 3 (cohorts 2, 3, 6, 7)).Tumor specific cohorts (melanoma, colorectal cancer) must have received specific prior approved therapiesPart 3 (Cohort 1) (BRAF V600 mutant melanoma): Prior BRAF V600 inhibitor therapy required, prior MEK inhibitor therapy required, and immune checkpoint inhibitor therapy required.Part 3 (Cohort 4) (BRAF V600E CRC): Minimum of 2 cycles of prior 5-FU based chemotherapy required. No prior BRAF inhibitor/EGFR inhibitor allowed. Participants with MSI-H/dMMR mCRC should receive prior immune checkpoint inhibitor therapy.Part 3 (Cohort 5) (BRAF V600E CRC): No more than 2 cycles of prior 5-FU based chemotherapy allowed. No prior BRAF inhibitor/EGFR inhibitors allowed. Participants with MSI-H/dMMR mCRC should receive prior immune checkpoint inhibitor therapy.
    Exclusion criteria
    • Brain metastasis larger than 4 cm
    • Systemic anti-cancer therapy or small molecule therapeutics ongoing at the start of study treatment.
    • History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO; history of retinal degenerative disease.
    • Concurrent neuromuscular disorder associated with elevated creatine kinase (CK).

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START San Antonio
    San Antonio, TX, United States, 78229
    Investigator
    Kyriakos Papadopoulos
    Status
    Recruiting
    Condition(s) Treated at Site
    Melanoma
    Non-Small Cell Lung Cancer
    Thyroid
    Glioma
    Bowel (Colorectal)