claturafenib (PF-07799933) / Pfizer - LARVOL DELTA

A next-generation BRAF inhibitor overcomes resistance to BRAF inhibition in patients with BRAF-mutant cancers using pharmacokinetics-informed dose escalation. (PubMed, Cancer Discov) - P1 | "We treated patients with treatment-refractory BRAF-mutant solid tumors in a first-in-human clinical trial (NCT05355701) that utilized a novel, flexible, pharmacokinetics-informed dose escalation design that allowed rapid achievement of PF-07799933 efficacious concentrations. PF-07799933 ± binimetinib was well-tolerated and resulted in multiple confirmed responses, systemically and in the brain, in BRAF-mutant cancer patients refractory to approved RAF inhibitors."

Journal • PK/PD data • Oncology • Solid Tumor

C4901001: A Study to Learn About the Study Medicine Called PF-07799544 as Monotherapy or in Combination in People With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=148 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2029 ➔ Aug 2027

Enrollment closed • Monotherapy • Trial completion date • Brain Cancer • Colorectal Cancer • Glioma • High Grade Glioma • Low Grade Glioma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF

Phase 1b study of a brain-penetrant MEK inhibitor, PF-07799544, plus next-generation BRAF dimer inhibitor, PF-07799933, in advanced BRAF-mutant melanoma. (ASCO 2026) - P1 | "PF-07799544 + PF-07799933 showed manageable safety and promising systemic and IC antitumor activity in heavily pretreated BRAF-mut advanced melanoma. Evaluation of dose expansion cohorts is ongoing."

IO biomarker • Metastases • P1 data • Endocrine Disorders • Melanoma • Nephrology • Renal Disease • Solid Tumor

A Study to Learn About the Study Medicine Called PF-07799544 in People With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=124 | Not yet recruiting | Sponsor: Pfizer

Combination therapy • New P1 trial • Brain Cancer • Colorectal Cancer • Endocrine Cancer • Gastrointestinal Cancer • Glioma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF

A Study to Learn About the Study Medicine Called PF-07799544 in People With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=124 | Not yet recruiting | Sponsor: Pfizer | Trial primary completion date: May 2026 ➔ Aug 2026

Combination therapy • Trial primary completion date • Brain Cancer • CNS Tumor • Colorectal Cancer • Endocrine Cancer • Gastrointestinal Cancer • Glioma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF

A Study to Learn About the Study Medicine Called PF-07799544 in People With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=124 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Brain Cancer • CNS Tumor • Colorectal Cancer • Endocrine Cancer • Gastrointestinal Cancer • Glioma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF

A Study to Learn About the Study Medicine Called PF-07799544 in People With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=124 | Recruiting | Sponsor: Pfizer | Trial completion date: Mar 2027 ➔ Sep 2028 | Trial primary completion date: Oct 2025 ➔ Mar 2027

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Colorectal Cancer • Endocrine Cancer • Gastrointestinal Cancer • Glioma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF

A Study to Learn About the Study Medicine Called PF-07799544 in People With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=124 | Recruiting | Sponsor: Pfizer | Trial completion date: Dec 2027 ➔ Jun 2027 | Trial primary completion date: Sep 2026 ➔ Jan 2026

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Colorectal Cancer • Endocrine Cancer • Gastrointestinal Cancer • Glioma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF

C4901001: A Study to Learn About the Study Medicine Called PF-07799544 in People With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=124 | Recruiting | Sponsor: Pfizer | Trial completion date: Apr 2029 ➔ Oct 2028 | Trial primary completion date: Oct 2027 ➔ Feb 2027

Trial completion date • Trial primary completion date • Brain Cancer • Colorectal Cancer • Glioma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF

C4901001: A Study to Learn About the Study Medicine Called PF-07799544 as Monotherapy or in Combination in People With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=124 | Recruiting | Sponsor: Pfizer | Trial completion date: Feb 2029 ➔ Jun 2029

Monotherapy • Trial completion date • Brain Cancer • Colorectal Cancer • Glioma • High Grade Glioma • Low Grade Glioma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF

C4901001: A Study to Learn About the Study Medicine Called PF-07799544 in People With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=124 | Recruiting | Sponsor: Pfizer | Trial completion date: Sep 2028 ➔ Aug 2029 | Trial primary completion date: Mar 2027 ➔ Feb 2028

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Colorectal Cancer • Endocrine Cancer • Glioma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF

Relative Bioavailability and Impact of Rabeprazole for PF-07799933, Food-Effect for PF-07799933 and PF-07799544 (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed

Trial completion

Relative Bioavailability and Impact of Rabeprazole for PF-07799933, Food-Effect for PF-07799933 and PF-07799544 (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting

Enrollment closed

A Study to Learn About the Study Medicine Called PF-07799933 in People With Advanced Solid Tumors With BRAF Alterations. (clinicaltrials.gov) - P1 | N=267 | Recruiting | Sponsor: Pfizer | Trial completion date: Aug 2030 ➔ Oct 2029 | Trial primary completion date: Feb 2029 ➔ Apr 2028

Trial completion date • Trial primary completion date • Brain Cancer • Colorectal Cancer • Glioma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF • CYP3A4 • MSI

Relative Bioavailability and Impact of Rabeprazole for PF-07799933, Food-Effect for PF-07799933 and PF-07799544 (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Pfizer

New P1 trial

A Study to Learn About the Study Medicine Called PF-07799933 in People With Advanced Solid Tumors With BRAF Alterations. (clinicaltrials.gov) - P1 | N=267 | Recruiting | Sponsor: Pfizer | Trial completion date: May 2030 ➔ Aug 2030 | Trial primary completion date: Nov 2028 ➔ Feb 2029

Trial completion date • Trial primary completion date • Brain Cancer • Colorectal Cancer • Glioma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF • CYP3A4 • MSI

Advancing next-generation pipeline of novel mechanisms and differentiated combinations across solid tumors (Businesswire) - "Updated Phase 2 data for PF‑08634404 (PF’4404), a novel bispecific antibody targeting PD-1 and VEGF, as monotherapy in first-line PD-L1-expressing NSCLC...Updated results from a Phase 1 study of sigvotatug vedotin (SV), a novel integrin β6 (IB6)–directed ADC, in combination with pembrolizumab in NSCLC...The first results from a Phase 2 study of neoadjuvant atirmociclib, a highly selective CDK4 inhibitor, in combination with letrozole versus letrozole alone in people with hormone receptor-positive (HR+), HER2- breast cancer....Findings from a Phase 1b study of a brain-penetrant MEK inhibitor, PF-07799544 (polfurmetinib), plus a next-generation BRAF inhibitor, PF-07799933 (claturafenib), in advanced BRAF-mutant melanoma."

P1 data • P2 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Melanoma • Non Small Cell Lung Cancer

Phase 1 trial of PF-07799933 (ARRY-440), a next-generation BRAF inhibitor, for BRAF-mutant cancers (AACR 2024) - P1 | "As of August 24, 2023 data cutoff, 30 pts with BRAF-mutant cancers started PF-07799933 treatment at 50 mg QD-450 mg BID as monotherapy (60%) or combination with binimetinib (27%) or cetuximab (all colorectal cancer [CRC]) (13%). A BRAF G466E+ (class III) adenoid cystic carcinoma pt had a molecular CR in ctDNA.CONCLUSION PF-07799933 treatment was associated with anti-tumor activity against BRAF V600- and non-V600-mutant cancers preclinically and in treatment-refractory pts. The novel, rapid PK-informed dose escalation design provides a new paradigm for accelerating testing of next-generation targeted therapies early in clinical development.TRIAL REGISTRATION NUMBER NCT05355701"

IO biomarker • P1 data • Adenoid Cystic Carcinoma • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Solid Tumor • ARAF

A Study to Learn About the Study Medicine Called PF-07799933 in People With Advanced Solid Tumors With BRAF Alterations. (clinicaltrials.gov) - P1 | N=267 | Recruiting | Sponsor: Pfizer | N=156 ➔ 267 | Trial completion date: Sep 2028 ➔ Apr 2030 | Trial primary completion date: Mar 2027 ➔ Oct 2028

Enrollment change • Trial completion date • Trial primary completion date • Brain Cancer • Colorectal Cancer • Glioma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF • CYP3A4

Synthesis of [ 11 C]PF-07799933 and evaluation of its whole-body distribution in NHP using PET (EANM 2025) - "The homogeneous brain uptake was measured and blocked with cold dosing. The effective dose was estimated to be 0.0042 mSv/MBq of injected activity, based on a dosimetry study in non-human primates, indicating that it is comparable to other C-11 PET radioligands."

CNS Disorders • CNS Tumor • BRAF

A Study to Learn About the Study Medicine Called PF-07799933 in People With Advanced Solid Tumors With BRAF Alterations. (clinicaltrials.gov) - P1 | N=156 | Recruiting | Sponsor: Pfizer | Trial completion date: Mar 2028 ➔ Aug 2028 | Trial primary completion date: Sep 2026 ➔ Feb 2027

Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Colorectal Cancer • Endocrine Cancer • Glioma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF

A Study to Learn About the Study Medicine Called PF-07799933 in People With Advanced Solid Tumors With BRAF Alterations. (clinicaltrials.gov) - P1 | N=156 | Recruiting | Sponsor: Pfizer | Trial completion date: Dec 2027 ➔ Mar 2028 | Trial primary completion date: Jun 2026 ➔ Sep 2026

Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Colorectal Cancer • Endocrine Cancer • Glioma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF

A Study to Learn About the Study Medicine Called PF-07799933 in People With Advanced Solid Tumors With BRAF Alterations. (clinicaltrials.gov) - P1 | N=156 | Recruiting | Sponsor: Pfizer | Trial completion date: Feb 2029 ➔ Nov 2027 | Trial primary completion date: Aug 2027 ➔ May 2026

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Colorectal Cancer • Endocrine Cancer • Gastrointestinal Cancer • Glioma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF

A new BRAF inhibitor breaks resistance barriers. (PubMed, Trends Cancer) - "In a recent Cancer Discovery paper, Yaeger et al. show that a next-generation BRAF inhibitor, PF-07799933, has widespread therapeutic activity in experimental models and patients who were refractory to treatment with approved BRAF inhibitors."

Journal • Oncology

A phase 1, open-label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of PF-07799544 (ARRY-134) as a single agent and in combination with PF-07799933 BRAF dimer inhibitor, in participants 16 years and older with advanced solid tumors. (ASCO 2024) - P1 | "Sub-study B: BRAFm melanoma (V600 and non-V600) will determine the MTDc/RDEc of the combination (Part 1 primary objective), followed by dose expansion cohorts (Part 2) (~80 participants): Cohort 1: BRAF V600 melanoma (asymptomatic and untreated bm permitted), Cohort 2: BRAF V600 melanoma (symptomatic bm), Cohort 3 BRAFm Class 2/3 melanoma (asymptomatic and untreated bm permitted); Sub-study C: BRAFm Class 2 or 3 advanced solid tumor Cohort 1 (asymptomatic and untreated bm permitted and Cohort 2 (symptomatic bm) (~20 each cohort). The main objectives of the dose expansion cohorts in all substudies, will be to evaluate anti-tumor activity, safety, PK and PD."

Clinical • Combination therapy • Metastases • P1 data • PK/PD data • Melanoma • Oncology • Solid Tumor