GSK6042981 / EMD Serono, GSK - LARVOL DELTA

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

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

New P3 trial • Gastrointestinal Cancer • 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=269 | Recruiting | Sponsor: IDRx Inc. - A GSK Company | Trial completion date: Sep 2026 ➔ Nov 2027 | Trial primary completion date: Apr 2026 ➔ Mar 2027

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

Tyrosine Kinase Inhibitors for Gastrointestinal Stromal Tumor After Imatinib Resistance. (PubMed, Pharmaceutics) - "Sunitinib, regorafenib, and ripretinib are currently approved as standard second-, third-, and fourth-line therapies, each demonstrating efficacy against distinct mutational profiles. Avapritinib, notably effective against PDGFRA D842V mutations, represents a milestone for previously untreatable subgroups. Several alternative agents-such as nilotinib, masitinib, sorafenib, dovitinib, pazopanib, and ponatinib-have shown varying degrees of success in refractory cases or specific genotypes. Investigational compounds, including crenolanib, bezuclastinib, famitinib, motesanib, midostaurin, IDRX-42, and olverembatinib, are under development to address resistant or wild-type GISTs...Future strategies include precision medicine approaches such as ctDNA-guided therapy, rational drug combinations, and novel drug delivery systems to optimize bioavailability and reduce toxicity. Ongoing research will be crucial for refining treatment sequencing and expanding therapeutic options,..."

Journal • Review • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

Progress on 14 key opportunities expected to launch 2025-2031 each with PYS potential above £2 billion (GSK Press Release) - "Phase III development programme for depemokimab COPD started with launch of ENDURA studies; Pivotal/Phase III trial starts planned in H2 25 for: potential cancer treatments GSK'227 B7H3 ADC for ES-SCLC and GSK'981 IDRx-42 for 2L GIST; efimosfermin for treatment of MASH"

New P3 trial • Trial status • Chronic Obstructive Pulmonary Disease • Gastrointestinal Stromal Tumor • Metabolic Dysfunction-Associated Steatohepatitis • Small Cell Lung Cancer

In vitro profiling of IDRX-42 against secondary and tertiary mutations (AP/AL) found in TKI-resistant GIST. (ASCO 2025) - "Funded by No funding sources reported Background: The majority of Gastrointestinal Stromal Tumors (GIST) harbor a KIT mutation and respond to imatinib (IM), but over time clinical resistance emerges due to secondary mutations...For example, sunitinib is potent against AP mutations (V654A, T670I), but has minimal activity against AL mutations...We also profiled IM and ripretinib (RIP) in the same cell line models... IDRX-42 has superior biochemical potency against a panel of primary and secondary KIT mutations compared with IM or RIP. Additionally, IDRX-42 has activity against K9 or K11 + V654A, and K9 or K11 + AL; However, K9 or K11 with T670I mutant kinases were resistant. Notably, none of these three profiled drugs had activity against K9 or K11 + AP/AL mutations."

Preclinical • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • Solid Tumor

M4205 (IDRX-42) is a highly selective and potent inhibitor of relevant oncogenic driver and resistance variants of KIT in cancer. (PubMed, Mol Cancer Ther) - "Imatinib, a small molecule tyrosine kinase inhibitor, is used successfully as first-line therapy for unresectable metastatic or recurrent GIST patients, but secondary resistance mutations in the KIT kinase domains frequently occur. The kinase selectivity profile of M4205 is superior to registered standard of care and investigational agents. M4205, now IDRX-42, is currently being investigated in a Phase 1 first-in-human study in participants with GIST."

Journal • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

GSK completes acquisition of IDRx, Inc. (GSK Press Release) - "GSK plc...announced that it has completed the acquisition of IDRx, Inc. (IDRx), a Boston-based, clinical-stage biopharmaceutical company dedicated to developing precision therapeutics for the treatment of gastrointestinal stromal tumours (GIST). As announced previously, the acquisition includes lead molecule IDRX-42, an investigational, highly selective tyrosine kinase inhibitor (TKI) that is designed to improve outcomes for patients with GIST."

M&A • Gastrointestinal Stromal Tumor

Emerging treatments for sarcoma: from 2024 onward. (PubMed, Expert Opin Emerg Drugs) - "While these strategies have demonstrated some success, the overall improvements in survival have often been modest, irrespective of the therapeutic modality. This underscores critical concerns regarding the true cost-benefit balance and the potential for adverse effects, particularly when evaluated over extended follow-up periods."

Journal • Review • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

GSK Enters Agreement to Acquire IDRx, Inc. (Businesswire) - "GSK plc...and IDRx, Inc...today announced that they have entered into an agreement under which GSK will acquire IDRx, a Boston-based, clinical-stage biopharmaceutical company dedicated to developing precision therapeutics for the treatment of GIST. Under the agreement, GSK will pay $1 billion upfront, with potential for an additional $150 million success-based regulatory approval milestone payment. The acquisition includes lead molecule, IDRX-42, a highly selective KIT TKI being developed as a first- and second-line therapy for the treatment of GIST."

Licensing / partnership • Solid Tumor

GSK is said to be nearing $1B deal to acquire U.S. biotech IDRx (MSN News) - "British pharma giant GSK...is closing in on a $1B buyout deal to acquire IDRx, a U.S. biotech focused on developing drugs for rare gastrointestinal tumors, The Financial Times reported Wednesday."

M&A • Gastrointestinal Stromal Tumor • Oncology

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

IN VITRO PROFILING OF IDRX-42 AGAINST SECONDARY MUTATIONS FOUND IN TKI-RESISTANT GIST (CTOS 2024) - "Objective: 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)...Although additional TKI drugs has been approved for the second-line (2L, sunitinib), 3L (regorafenib), and 4L/4L+ (ripretinib, RIP), these agents lack activity against the entire spectrum of known resistance mutations... IDRX-42 has superior biochemical potency against a panel of primary and secondary KIT mutations compared with IM or RIP. Additionally, IDRX-42 has activity against all tested K11 + secondary/tertiary mutations with the exception of K14 T670I. It should be noted that T670I is an infrequently reported secondary mutation compared to V654A or AL secondary mutations, possibly due to diminished enzymatic activity compared with the parental K11 mutant kinase."

Preclinical • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

IDRx Announces Updated Phase 1 Data from Ongoing Phase 1/1b StrateGIST 1 Trial of IDRX-42 in Advanced Gastrointestinal Stromal Tumors (GIST) at CTOS 2024 (Businesswire) - P1/1b | N=240 | StrateGIST 1 (NCT05489237) | Sponsor: IDRx, Inc. | "'With FDA alignment now in place, we plan to conduct StrateGIST 3, a randomized, Phase 3 registrational trial which will evaluate the efficacy and safety of IDRX-42 as compared to sunitinib in second-line GIST patients.'...As of the data cut-off date of September 30, 2024, 89 patients have been treated with IDRX-42 in the Phase 1 portion of the ongoing StrateGIST 1 trial across dose cohorts ranging from 120 mg once daily (QD) to 1200 mg total daily dose (600 mg twice daily (BID))....The ORR by modified RECIST v1.1 in the total efficacy evaluable population was 29% (25/87) treated across all lines of therapy, including one complete response (CR) and 24 partial responses (PRs). Two of the PRs were awaiting confirmation at the time of the data cut: At the 400 mg capsule/300 mg tablet QD recommended Phase 1b dose (RP1bD), the ORR was 26% (10/38) in the total efficacy evaluable population."

New P3 trial • P1 data • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Solid Tumor

IDRx Announces $120 Million Series B Financing to Advance Potential Best-in-class New Treatment for Gastrointestinal Stromal Tumor (GIST) (Businesswire) - "IDRx, Inc...announced the completion of an oversubscribed $120 million Series B Preferred Stock financing....IDRx plans to use the proceeds from the financing to support the ongoing Phase 1/1b StrateGIST 1 study of its lead product candidate IDRX-42, a potent, oral, highly selective KIT inhibitor targeting all major categories of activating and resistance mutations in patients with KIT-mutant GIST. Additionally, proceeds will be used to fund the expected initiation of the first pivotal study for IDRX-42 in patients with second-line GIST....In addition, the U.S. Food and Drug Administration (FDA) has recently granted Fast Track designation to IDRX-42 for the treatment of GIST after disease progression on or intolerance to imatinib."

Fast track • Financing • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Solid Tumor

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

IDRx Reports Updated Preliminary Phase 1 Data from Ongoing Phase 1/1b StrateGIST 1 Trial Supporting Best-in-Class Potential for IDRX-42 in Patients with GIST (Businesswire) - P1 | N=240 | StrateGIST 1 (NCT05489237) | Sponsor: IDRx, Inc. | "IDRx, Inc...announced updated preliminary clinical data from the Phase 1 portion of the company’s ongoing StrateGIST 1 study of IDRX-42 in patients with advanced gastrointestinal stromal tumors (GIST)....The objective response rate (ORR) by modified RECIST v1.1 in the efficacy evaluable population was 23% (15/66) treated across all lines of therapy, of which all were partial responses (12 confirmed PRs, 3 pending confirmation). The ORR across second line patients was 43% (6/14; 4 confirmed PRs, 2 pending confirmation). In analyses of circulating tumor DNA (ctDNA), reductions in mutant allele fraction were observed consistently across KIT mutations detected in baseline samples. Reductions in mutant allele fraction, including to undetectable levels, as best response were observed in exon 9 and 11 activating mutations, and in resistance mutations exon 13, 14, and 17."

P1 data • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Solid Tumor

A First-in-human (FIH) Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) [Study ID: StrateGIST 1] (clinicaltrials.gov) - P1 | N=240 | Recruiting | Sponsor: IDRx, Inc. | N=143 ➔ 240

Enrollment change • Metastases • Stroma • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • PDGFRA

KIT/PDGFRA inhibitors for the treatment of gastrointestinal stromal tumors: getting to the gist of the problem. (PubMed, Expert Opin Investig Drugs) - "Despite the outstanding results of first-line imatinib in advanced GIST, resistance ultimately occurs mainly through secondary mutations in KIT/PDGFRA...However, it is now recognized that the situation is more intricate, with various factors interacting with KIT and PDGFRA, playing a crucial role in the response and resistance to treatments. Future strategies in the management of advanced GIST should integrate driver inhibition with the blockade of other molecules to enhance cell death and establish enduring responses in patients."

Journal • Stroma • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

PHASE 1 STUDY OF IDRX-42 IN PATIENTS WITH ADVANCED GASTROINTESTINAL STROMAL TUMORS RESISTANT TO PRIOR SYSTEMIC THERAPY: EARLY RESULTS (CTOS 2023) - "In xenograft models expressing secondary resistance mutations in KIT exon 13, IDRX-42 treatment resulted in potent and dose-dependent antitumor activity superior to the second-line standard of care agent, sunitinib (De Sutter 2023). IDRX-42 demonstrates promising antitumor activity and a favorable safety profile in a pre-treated group of pts with advanced/metastatic GISTs. IDRX-42 has a broad and potent KIT inhibitory profile including primary driver and resistance mutations. Phase 1b will evaluate IDRX-42 in pts after failure of first-line imatinib as well as after failure of later lines of therapy."

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

IDRx Presents Preliminary Clinical Data from Ongoing Phase 1 StrateGIST Study at CTOS 2023 Supporting Best-in-Class Potential of IDRX-42 in Patients with GIST (Businesswire) - P1 | N=143 | StrateGIST (NCT05489237) | Sponsor: IDRx, Inc. | "IDRx, Inc...today announced preliminary clinical data from the dose escalation portion of the company’s ongoing Phase 1 StrateGIST study....Confirmed partial responses (PRs)...in four patients (at 120 mg QD, 400 mg QD, and 600 mg QD [n=2]). Although an MTD has not yet been reached, a 68% (19/28 patients) clinical benefit rate (confirmed complete response/PR or stable disease ≥16 weeks) was observed across the initial doses studied to date. 4/28 patients are on study for <16 weeks and continuing on study drug. Tumor shrinkage and confirmed partial responses were observed across all major classes of KIT mutational variants, including both primary driver mutations in exons 9 and 11, and secondary resistance mutations in exons 13 and 17. Additionally, notable reductions in mutant allele fraction were observed in circulating tumor DNA across these classes of KIT variants."

P1 data • Gastrointestinal Stromal Tumor • Oncology • Solid Tumor

A First-in-human (FIH) Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (clinicaltrials.gov) - P1 | N=143 | Recruiting | Sponsor: IDRx, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • PDGFRA

Antitumor Efficacy of the Novel KIT Inhibitor IDRX-42 (Formerly M4205) in Patient- and Cell Line–Derived Xenograft Models of Gastrointestinal Stromal Tumor (GIST) (Clin Cancer Res) - "IDRX-42 (25 mg/kg) caused tumor volume shrinkage in UZLX-GIST25, GIST882, and UZLX-GIST2B, with a relative decrease to 45.6%, 57.3%, and 35.1% on the last day as compared with baseline, and tumor growth delay (160.9%) compared with control in UZLX-GIST9. Compared with controls, IDRX-42 (25 mg/kg) induced a significant decrease in mitosis."

Preclinical • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor