brimarefenib (BGB-3245) / MapKure, BeOne Medicines, EMD Serono - LARVOL DELTA

BGB-3245-EGFR-001: A Study to Investigate BGB-3245 (Brimarafenib) With Panitumumab in Participants With Advanced or Metastatic RAS Mutant Colorectal and Pancreatic Ductal Cancers (clinicaltrials.gov) - P1 | N=13 | Terminated | Sponsor: MapKure, LLC | N=64 ➔ 13 | Trial completion date: May 2027 ➔ Mar 2025 | Recruiting ➔ Terminated | Trial primary completion date: May 2027 ➔ Mar 2025; Funding terminated due to business reasons

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Colorectal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • BRAF

Mirdametinib + BGB-3245 in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=23 | Terminated | Sponsor: SpringWorks Therapeutics, Inc. | Trial completion date: Jun 2027 ➔ Jan 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Oct 2026 ➔ Jan 2025; Lack of tolerability of Brimarafenib when given in combination of Mirdametinib

Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • KRAS • NRAS

BGB-3245-AU-001: Study of Safety, Pharmacokinetics, and Antitumor Activity of BGB-3245 in Participants with Advanced or Refractory Tumors (clinicaltrials.gov) - P1 | N=110 | Active, not recruiting | Sponsor: MapKure, LLC | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2025 ➔ Nov 2025 | Trial primary completion date: Jun 2025 ➔ Nov 2025

Enrollment closed • Trial completion date • Trial primary completion date • Colorectal Cancer • Oncology • Solid Tumor • BRAF • KRAS • NRAS

SpringWorks Therapeutics Reports Preliminary Fourth Quarter and Full Year 2024 Financial Results and Provides Business Updates at 43rd Annual J.P. Morgan Healthcare Conference (GlobeNewswire) - "Emerging Pipeline: SpringWorks expects additional data to be presented by MapKure from the brimarafenib monotherapy trial in the second half of 2025. Continue enrolling patients in Phase 1 trial of SW-682 in Hippo-mutant solid tumors. File an Investigational New Drug (IND) application for SW-3431 by the end of 2025."

Enrollment status • IND • P1 data • Oncology • Solid Tumor

SpringWorks Therapeutics Reports Third Quarter 2024 Financial Results and Recent Business Highlights (GlobeNewswire) - "A Phase 1b trial evaluating brimarafenib (BGB-3245) in adult patients with RAF mutant solid tumors is ongoing; additional data from the dose expansion portion of the study is expected to be presented in the second half of 2025."

P1 data • Oncology • Solid Tumor

Mirdametinib + BGB-3245 in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=23 | Active, not recruiting | Sponsor: SpringWorks Therapeutics, Inc. | Recruiting ➔ Active, not recruiting | N=136 ➔ 23

Combination therapy • Enrollment change • Enrollment closed • Metastases • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • KRAS • NRAS

BGB-3245-AU-001: Study of Safety, Pharmacokinetics, and Antitumor Activity of BGB-3245 in Participants With Advanced or Refractory Tumors (clinicaltrials.gov) - P1 | N=114 | Recruiting | Sponsor: MapKure, LLC | Trial primary completion date: Aug 2024 ➔ Jun 2025

Metastases • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • KRAS • NRAS

SpringWorks Therapeutics Reports Second Quarter 2024 Financial Results and Recent Business Highlights (GlobeNewswire) - "The Company expects to complete the submission of an MAA for mirdametinib for the treatment of children and adults with NF1-PN in the European Union in the second half of 2024....SpringWorks expects to publish the ReNeu trial results in a peer-reviewed journal in the second half of 2024....A Phase 1b trial evaluating brimarafenib (BGB-3245) in adult patients with RAF mutant solid tumors is ongoing; additional data from the dose expansion portion of the study is expected to be presented in the first half of 2025. SpringWorks initiated a Phase 1a trial of SW-682, an investigational novel, oral, potent, and selective pan-TEAD inhibitor, in Hippo-mutant solid tumors in the second quarter of 2024."

EMA filing • P1 data • P2b data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Neurofibromatosis • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

SpringWorks Therapeutics Reports First Quarter 2024 Financial Results and Highlights Recent Business Updates (GlobeNewswire) - "Emerging Pipeline: (i) On track to present additional data from the dose expansion portion of the Phase 1b trial evaluating brimarafenib (BGB-3245) in adult patients with RAF mutant solid tumors in the second half of 2024...; (ii) On track to initiate a Phase 1a trial of SW-682, an investigational novel, oral, potent, and selective pan-TEAD inhibitor, in Hippo-mutant solid tumors in the second quarter of 2024."

New P1 trial • P1 data • Solid Tumor

A Study to Investigate BGB-3245 (Brimarafenib) With Panitumumab in Participants With Advanced or Metastatic RAS Mutant Colorectal and Pancreatic Ductal Cancers (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: MapKure, LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • BRAF

SpringWorks Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Highlights Recent Business Updates (GlobeNewswire) - "The FDA cleared the Investigational New Drug (IND) application submitted by MapKure for a combination study of brimarafenib with panitumumab, a monoclonal antibody targeting EGFR, in colorectal and pancreatic cancer patients with known MAPK pathway mutations. MapKure expects to initiate a Phase 1b trial in the first quarter of 2024....The FDA cleared the IND application for SW-682, a novel, oral, potent, and selective TEA Domain inhibitor designed to treat tumors driven by Hippo pathway mutations. SpringWorks plans to initiate a Phase 1a trial of SW-682 in Hippo mutant solid tumors in the first half of 2024."

IND • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

A Study to Investigate BGB-3245 (Brimarafenib) With Panitumumab in Participants With Advanced or Metastatic RAS Mutant Colorectal and Pancreatic Ductal Cancers (clinicaltrials.gov) - P1 | N=64 | Not yet recruiting | Sponsor: MapKure, LLC

Metastases • New P1 trial • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • BRAF

BGB-3245-AU-001: Study of Safety, Pharmacokinetics, and Antitumor Activity of BGB-3245 in Participants With Advanced or Refractory Tumors (clinicaltrials.gov) - P1 | N=114 | Recruiting | Sponsor: MapKure, LLC | Phase classification: P1a/1b ➔ P1

Phase classification • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • KRAS • NRAS

BGB-3245-AU-001: Study of Safety, Pharmacokinetics, and Antitumor Activity of BGB-3245 in Participants With Advanced or Refractory Tumors (clinicaltrials.gov) - P1a/1b | N=114 | Recruiting | Sponsor: MapKure, LLC | Trial completion date: Aug 2024 ➔ Jun 2025 | Trial primary completion date: May 2024 ➔ Aug 2024

Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • KRAS • NRAS

BGB-3245-AU-001: Study of Safety, Pharmacokinetics, and Antitumor Activity of BGB-3245 in Participants With Advanced or Refractory Tumors (clinicaltrials.gov) - P1a/1b | N=114 | Recruiting | Sponsor: MapKure, LLC | N=168 ➔ 114

Enrollment change • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • KRAS • NRAS

A first-in-human, phase 1a/1b, open-label, dose-escalation and expansion study to investigate the safety, pharmacokinetics, and antitumor activity of the RAF dimer inhibitor BGB-3245 in patients with advanced or refractory tumors (AACR 2023) - "BGB-3245 has a manageable safety profile and a generally dose-proportional PK. Antitumor activity was observed in pts with no approved targeted therapy options. The safety and early efficacy profile of BGB-3245 supports further investigation in selected MAPK-altered tumors."

Clinical • Metastases • P1 data • PK/PD data • Appendix Cancer • Biliary Cancer • Cholangiocarcinoma • Endometrial Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Solid Tumor • KRAS • NRAS • PIK3CA

MapKure, BeiGene and SpringWorks Present Clinical Data on BGB-3245, a Selective Next-Generation B-RAF Inhibitor, in Adult Patients with Advanced or Refractory Solid Tumors at the American Association for Cancer Research Annual Meeting 2023 (Businesswire) - P1 | N=168 | NCT04249843 | "MapKure...announced that they will present updated clinical data from the Phase 1a/1b study of BGB-3245, an investigational, selective RAF dimer inhibitor, in adult patients with advanced or refractory solid tumors harboring MAPK pathway aberrations. The data are being presented today in an oral presentation at the American Association for Cancer Research (AACR) Annual Meeting 2023, taking place in Orlando, Florida....The disease control rate was 79% and clinical benefit rate was 42%. Objective responders include patients with tumors harboring BRAF V600E that had progressed on prior BRAF/MEK inhibitors with or without checkpoint inhibitor treatment, BRAF Class II mutation, BRAF fusion, NRAS and KRAS mutations."

P1 data • Oncology • Solid Tumor

SpringWorks Therapeutics Highlights 2022 Accomplishments and Anticipated Milestones for 2023 at the 41st Annual J.P. Morgan Healthcare Conference (GlobeNewswire) - "Anticipated 2023 Key Milestones: Present additional data from BeiGene-sponsored Phase 1b/2 trial evaluating mirdametinib in combination with lifirafenib in adult patients with RAS/RAF mutant and other MAPK pathway aberrant solid tumors at a medical conference in the first half of 2023; Dose first patient in BGB-3245 + mirdametinib combination study in MAPK-mutant solid tumors in the first half of 2023; File Investigational New Drug Application for TEAD inhibitor SW-682."

IND • P1/2 data • Trial status • Oncology • Solid Tumor

SpringWorks Therapeutics Highlights 2022 Accomplishments and Anticipated Milestones for 2023 at the 41st Annual J.P. Morgan Healthcare Conference (GlobeNewswire) - "Anticipated 2023 Key Milestones: Continue enrollment in the Phase 2 trial of nirogacestat in patients with OvGCT; Expand data set with additional clinical data of nirogacestat in combination with BCMA-directed therapies and initiate additional planned Phase 1 collaborator studies; Present additional clinical data from the Phase 1 trial evaluating BGB-3245 in adult patients with RAF mutant solid tumors at a medical conference in the first half of 2023."

Clinical data • Enrollment status • New P1 trial • P1 data • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Mirdametinib + BGB-3245 in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=136 | Recruiting | Sponsor: SpringWorks Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • KRAS • NRAS

SpringWorks Therapeutics Reports Third Quarter 2022 Financial Results and Recent Business Highlights (GlobeNewswire) - "Biomarker-Defined Metastatic Solid Tumors: The BeiGene-sponsored Phase 1b/2 trial evaluating mirdametinib with BeiGene’s RAF dimer inhibitor, lifirafenib, in adult patients with RAS/RAF mutant and other MAPK pathway aberrant solid tumors is ongoing. SpringWorks expects data from this trial to be presented at a medical conference in the first half of 2023. The Phase 1 trial evaluating BGB-3245...in adult patients with RAF mutant solid tumors is ongoing. SpringWorks expects data from this trial to be presented at a medical conference in the first half of 2023. BGB-3245 monotherapy is advancing into cohort expansion studies and SpringWorks expects to begin dosing a Phase 1/2a combination study of BGB-3245 and mirdametinib in the first half of 2023."

P1 data • P1/2 data • Trial status • Oncology • Solid Tumor

Vertical inhibition of the MAPK pathway as potential treatment strategy in NRAS-mutant melanoma (AACR-NCI-EORTC 2022) - "Material and The combinatorial effects of mirdametinib with the pan-RAF dimer inhibitor lifirafenib or BGB-3245 were evaluated in a cohort of 14 primary and patient-derived melanoma cell lines harboring NRAS Q61 mutations. These data support the evaluation of MAPK pathway vertical inhibition through combination of MEK and panRAF inhibitors for treatment of patients with RAS mutations. Lastly, NRAS Q61 may serve as a prospective biomarker for patient stratification in trials assessing the combination of MEK and pan-RAF inhibitors in mutant melanoma."

Melanoma • Oncology • Solid Tumor • NRAS

BGB-3245-AU-001: Study of Safety, Pharmacokinetics, and Antitumor Activity of BGB-3245 in Participants With Advanced or Refractory Tumors (clinicaltrials.gov) - P1a/1b | N=168 | Recruiting | Sponsor: MapKure, LLC | Trial completion date: Jun 2023 ➔ Jun 2024 | Trial primary completion date: May 2023 ➔ May 2024

Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Solid Tumor • BRAF • KRAS • NRAS

Mirdametinib + BGB-3245 in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=136 | Not yet recruiting | Sponsor: SpringWorks Therapeutics, Inc.

Combination therapy • New P1/2 trial • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • KRAS • NRAS

SpringWorks Therapeutics Reports Second Quarter 2022 Financial Results and Recent Business Highlights (GlobeNewswire) - "BGB-3245 Monotherapy to Advance into Cohort Expansion Studies and Combination Study of BGB-3245 and Mirdametinib Planned to Initiate in 2H 2022....Initial clinical data from the BeiGene-sponsored Phase 1b/2 trial evaluating mirdametinib with BeiGene’s RAF dimer inhibitor, lifirafenib, in adult patients with RAS/RAF mutant and other MAPK pathway aberrant solid tumors...SpringWorks expects these data to be presented at a medical conference in the second half of 2022."

Enrollment status • P1/2 data • Oncology • Solid Tumor