velzatinib (GSK6042981) / EMD Serono, GSK - LARVOL DELTA

Velzatinib exhibits broad c-KIT mutation coverage in a novel panel of Ba/F3 mutant cell models representing the majority of secondary resistance mutations observed clinically in gastrointestinal stromal tumors (GIST) (ESMO 2026) - No abstract available

Clinical • Stroma • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT

Molecular Response (MR) in KIT circulating tumor DNA (ctDNA) from StrateGIST 1: A Phase 1/1b Study of Velzatinib (IDRX-42) in Patients (pts) With Advanced Gastrointestinal Stromal Tumors (GIST) (ESMO 2026) - No abstract available

Circulating tumor DNA • Clinical • Metastases • P1 data • Stroma • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

A Study of Velzatinib in Participants With Metastatic and/or Unresectable GIST After Imatinib, Sunitinib, Regorafenib, and Pimitespib (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: GlaxoSmithKline | Not yet recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

StrateGIST 1: A first-in-human (FIH), phase 1 study of IDRX-42 in patients with metastatic gastrointestinal stromal tumors resistant to prior treatment with tyrosine kinase inhibitors (TKIs). (ASCO 2024) - P1 | "We present data from the ongoing FIH phase (ph) 1 study evaluating IDRX-42 in patients (pts) with metastatic GIST in 2 nd or later lines of therapy after failure of imatinib and other drugs. IDRX-42 demonstrates promising clinical activity and a favorable safety profile in patients with advanced GIST following resistance to prior TKIs. Dose finding continues, and additional cohorts are ongoing."

Clinical • Metastases • P1 data • Stroma • Anemia • Fatigue • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Hematological Disorders • Oncology • Sarcoma

Velzatinib (IDRX-42) as 1L or 2L therapy for advanced gastrointestinal stromal tumors (GISTs) by KIT mutation status: A subset analysis of the phase 1/1b StrateGIST 1 study. (ASCO 2026) - P1 | "Funded by GSK Clinical Trial Registration Number: NCT05489237 Background: Most GISTs present with activating KIT mutations (exons 9/11) initially responsive to imatinib, but many progress due to diverse KIT resistance mutations (largely in exons 13/14/17/18). Velzatinib exhibited promising activity and tolerable safety as 1L and 2L therapy across clinically relevant KIT mutations for pts with advanced GIST. These data support further study of velzatinib, including in 1L pts, to address the need for therapeutic options with broad coverage of clinically relevant GIST mutations. This study (NCT05489237) is funded by GSK."

Metastases • P1 data • Stroma • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT

StrateGIST 3: A Study of IDRX-42 (GSK6042981) Versus (vs) Sunitinib in Participants With Gastrointestinal Stromal Tumors After Imatinib Therapy (clinicaltrials.gov) - P3 | N=450 | Recruiting | Sponsor: GlaxoSmithKline | Initiation date: Apr 2026 ➔ Dec 2025

Trial initiation date • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

Individual Patient Expanded Access for Velzatinib (GSK6042981) in Patients With Gastrointestinal Stromal Tumours With KIT Mutations (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: GlaxoSmithKline

New trial • Gastrointestinal Cancer • Oncology • Sarcoma • KIT

THE NOVEL KIT INHIBITOR IDRX-42 SHOWS PROMISING ACTIVITY IN 2ND AND LATER-LINE GASTROINTESTINAL STROMAL TUMORS: RESULTS FROM A PHASE 1 STUDY (STRATEGIST 1) (CTOS 2024) - No abstract available

P1 data • Stroma • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

Efficacy of velzatinib (IDRX-42) in patients with advanced/metastatic GIST by line of therapy and circulating tumor DNA response in the phase 1/1b StrateGIST 1 trial. (ASCO 2026) - P1 | "Velzatinib has broad activity against clinically relevant KIT mutations in pts with advanced and/or metastatic GIST and can substantially reduce ctDNA levels across a broad spectrum of clinically meaningful KIT mutation profiles. Baseline exon-level KIT mutation status and ctDNA detectability provide potentially useful prognostic and predictive data, justifying further study to discern the relationship between clinical benefit and molecular response. This study (NCT05489237) is funded by GSK."

Circulating tumor DNA • Clinical • Metastases • P1 data • Gastrointestinal Stromal Tumor • Oncology • PDGFRA

A Study to Investigate Velzatinib Compared With Imatinib in Adult Participants With Previously Untreated Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (StrateGIST Frontline) (clinicaltrials.gov) - P3 | N=800 | Recruiting | Sponsor: GlaxoSmithKline | Not yet recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

A Study of Velzatinib in Participants With Metastatic and/or Unresectable GIST After Imatinib, Sunitinib, Regorafenib, and Pimitespib (clinicaltrials.gov) - P2 | N=24 | Not yet recruiting | Sponsor: GlaxoSmithKline

New P2 trial • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

StrateGIST 1: First-in-human Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (clinicaltrials.gov) - P1 | N=276 | Active, not recruiting | Sponsor: IDRX, Inc., a wholly owned subsidiary of GSK, LLC | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2028 ➔ Mar 2027

Enrollment closed • First-in-human • Trial completion date • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

StrateGIST 3: A Study of IDRX-42 (GSK6042981) Versus (vs) Sunitinib in Participants With Gastrointestinal Stromal Tumors After Imatinib Therapy (clinicaltrials.gov) - P3 | N=450 | Sponsor: GlaxoSmithKline

Trial initiation date • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

StrateGIST 3: A randomized, phase 3 study of velzatinib (IDRX-42) versus sunitinib in patients with advanced gastrointestinal stromal tumors after imatinib therapy. (ASCO 2026) - P3 | "This trial is now recruiting. This study (NCT07218926) is funded by GSK."

Clinical • Metastases • P3 data • Stroma • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

First results for velzatinib in first-line (1L) advanced gastrointestinal stromal tumors (GIST) will show promising activity and tolerability across KIT mutations. These data have accelerated initiation of the StrateGIST Frontline phase III clinical trial given the need for therapies in 1L that broadly inhibit clinically relevant KIT variants, a key driver of relapse today. (GSK Press Release) - "Data for velzatinib across clinically relevant KIT mutations in all lines, including 1L and second-line (2L) advanced GIST, will show encouraging anti-tumor activity and tolerability supporting the potential for a differentiated clinical profile (ASCO oral presentation abstract #11501); Analyses of velzatinib will show broad activity and substantial circulating tumor DNA (ctDNA) clearance of clinically meaningful KIT mutations and inhibition of GIST tumor cells (ASCO rapid oral presentation abstract #11520)."

P1 data • Trial status • Gastrointestinal Stromal Tumor

Sylvester Comprehensive Cancer Center Unveils ASCO 2026 Highlights (Bioengineer.org) - "A prominent highlight is the phase 3 randomized MajesTEC-9 study, which evaluates teclistamab monotherapy against the investigator’s choice of pomalidomide, bortezomib, and dexamethasone or carfilzomib and dexamethasone in patients suffering from relapsed refractory multiple myeloma....In gastrointestinal oncology, Dr. Jonathan Trent and colleagues have co-authored significant phase 1/1b and phase 3 trials assessing bezuclastinib combined with sunitinib versus sunitinib monotherapy, as well as velzatinib’s efficacy based on KIT mutation status in gastrointestinal stromal tumors (GISTs)....Sarcoma research...includes a pivotal phase 3 investigation of catequentinib hydrochloride (AL3818) monotherapy in patients with advanced alveolar soft part sarcoma (ASPS), co-authored by Dr. Jonathan C. Trent."

P1 data • P3 data • Alveolar Soft Tissue Sarcoma • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Multiple Myeloma

A Study to Investigate Velzatinib Compared With Imatinib in Adult Participants With Previously Untreated Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (StrateGIST Frontline) (clinicaltrials.gov) - P3 | N=800 | Not yet recruiting | Sponsor: GlaxoSmithKline

New P3 trial • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

StrateGIST 1: First-in-human Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (clinicaltrials.gov) - P1 | N=278 | Recruiting | Sponsor: IDRX, Inc., a wholly owned subsidiary of GSK, LLC | Trial completion date: Nov 2027 ➔ Jun 2028 | Trial primary completion date: Nov 2027 ➔ Mar 2027

First-in-human • Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

In vitro profiling of IDRX-42 and NB003 against secondary and tertiary (AP/AL) mutations found in TKI-resistant GIST (AACR 2026) - "Approximately 70-75% of Gastrointestinal stromal tumor (GIST) harbor a KIT mutation and patients with KIT-mutant GIST have durable responses to front-line imatinib (IM)...For example, sunitinib (SU) is potent against AP mutations (V654A, T670I), but has minimal activity against AL mutations. Conversely, ripretinib (RIP) has minimal activity against AP mutations...Ideally, future development of these newer agents should focus on earlier lines of therapy, prior to the development of AP+ AL mutations. The pan-resistance of AP/AL mutations to existing TKIs indicates the need to develop new drugs to target these resistance mutations."

Preclinical • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT

A Study of IDRX-42 (GSK6042981) Versus (vs) Sunitinib in Participants With Gastrointestinal Stromal Tumors After Imatinib Therapy (clinicaltrials.gov) - P3 | N=450 | Recruiting | Sponsor: GlaxoSmithKline

Trial initiation date • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

300383: Phase 3 Study of IDRX-42 (GSK6042981) vs Sunitinib in Participants with Metastatic and/or Unresectable GIST after Imatinib (clinicaltrialsregister.eu) - P2/3 | N=148 | Not yet recruiting | Sponsor: Glaxosmithkline Research & Development Limited

New P2/3 trial • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

A Study of IDRX-42 (GSK6042981) Versus (vs) Sunitinib in Participants With Gastrointestinal Stromal Tumors After Imatinib Therapy (clinicaltrials.gov) - P3 | N=450 | Recruiting | Sponsor: GlaxoSmithKline | Not yet recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

UPDATED RESULTS FROM STRATEGIST 1: A PHASE 1/1B STUDY OF IDRX-42 (GSK6042981A) IN PATIENTS (PTS) WITH ADVANCED GASTROINTESTINAL STROMAL TUMORS (GIST) (CTOS 2025) - "IIDRX-42 exhibits promising activity and safety in previously treated GIST, warranting further study in early-line pts.Table 1: Clinical Activity per Modified RECIST v1.1"

Clinical • Metastases • P1 data • Stroma • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • PDGFRA

BIOCHEMICAL PROFILING OF IDRX-42 AND NB003 AGAINST KIT PRIMARY, SECONDARY, AND TERTIARY MUTATIONS (CTOS 2025) - No abstract available

Gastrointestinal Stromal Tumor • Oncology

StrateGIST 1: First-in-human Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (clinicaltrials.gov) - P1 | N=278 | Recruiting | Sponsor: IDRx Inc. - A GSK Company | Trial primary completion date: Mar 2027 ➔ Nov 2027

First-in-human • Trial primary completion date • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • PDGFRA