safusidenib (DS-1001) / Daiichi Sankyo, Nuvation Bio - LARVOL DELTA

Perioperative IDH inhibition in treatment-naive IDH-mutant glioma: a pilot trial. (PubMed, Nat Med) - P1 | "Here we conducted a single-arm, open-label feasibility perioperative trial in patients with mIDH1 low-grade glioma, treatment naive to radiation and chemotherapy, with safusidenib (AB-218/DS-1001b), an orally available small-molecule inhibitor of mIDH1...The study shows the safety and feasibility of this perioperative approach, which can be applied broadly in clinical trial design, serving as proof of concept for advancing drug development in glioma. ClinicalTrials.gov registration: NCT05577416 ."

Journal • Brain Cancer • Glioma • Oncology • Solid Tumor

AB-218-IIT-201: A Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: Melbourne Health | Trial completion date: Dec 2025 ➔ Mar 2025 | Trial primary completion date: Dec 2024 ➔ Mar 2025 | Recruiting ➔ Completed

Trial completion • Trial completion date • Trial primary completion date • Brain Cancer • Glioma • Oncology • Solid Tumor

Long-term administration of the mutant IDH inhibitor DS-1001b suppresses the growth of IDH1-mutant glioma in vitro and in mouse xenograft models and alters epigenetic profiles. (PubMed, Acta Neuropathol) - "Metabolomic analyses further demonstrated a significant reduction in asparagine in A1074, consistent with the activation of L-asparaginase-mediated pathways. Collectively, these findings indicate that sustained DS-1001b administration exerts antitumor effects in IDH1-mutant glioma mouse models and induces transcriptomic, epigenetic, and metabolic reprogramming."

Journal • Preclinical • Astrocytoma • Brain Cancer • CNS Tumor • Glioma • Oligodendroglioma • Oncology • Solid Tumor • IDH1

Nuvation Bio…announced finalization of a protocol amendment to the ongoing global SIGMA study (also known as G203; NCT05303519) of safusidenib that expands it to a Phase 3 trial (Businesswire) - "SIGMA is evaluating the efficacy and safety of safusidenib versus placebo for the maintenance treatment of patients with high-risk or high-grade IDH1-mutant astrocytoma following standard-of-care....To support regulatory submissions for patients with astrocytoma, the protocol amendment significantly increases trial enrollment from 100 to 300 patients in the U.S., Australia and China....The trial will now also enroll a non-pivotal single-arm cohort to examine the efficacy and safety of safusidenib in chemotherapy- and radiotherapy-naïve patients with grade 3 IDH1-mutant oligodendroglioma....'We expect initial data for the separate oligodendroglioma cohort in 2027'."

Clinical protocol • P3 data • Astrocytoma • Oligodendroglioma

Study of DS-1001b in Patients With Gene IDH1-Mutated Gliomas (clinicaltrials.gov) - P1 | N=47 | Active, not recruiting | Sponsor: Daiichi Sankyo | Phase classification: P=N/A ➔ P1

Phase classification • Brain Cancer • Glioma • Oncology • Solid Tumor • IDH1

SIGMA (Safusidenib in IDH1 Mutant Glioma Maintenance) (clinicaltrials.gov) - P3 | N=365 | Recruiting | Sponsor: Nuvation Bio Inc. | Phase classification: P2 ➔ P3 | N=125 ➔ 365 | Trial completion date: Mar 2028 ➔ Dec 2030 | Trial primary completion date: Dec 2027 ➔ Dec 2028

Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Oligodendroglioma • Oncology • Solid Tumor • ATRX • CDKN2A • CDKN2B • IDH1

A perioperative study of safusidenib in patients with IDH1 mutated glioma (ESMO 2024) - P1 | "Taken together, these results provide detailed understanding on mechanism of IDH inhibition for glioma, and a proof of concept of the perioperative approach to advance drug development in glioma."

Clinical • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • IDH1

Nuvation Bio is progressing the ongoing G203 study in high-grade IDH1-mutant gliomas, with a protocol amendment on track to finalize the study as a global Phase 3 to support potential regulatory approvals (Businesswire) - "The primary endpoint is PFS as assessed by Blinded Independent Central Review per Response Assessment in Neuro-Oncology 2.0, which the FDA agreed could support full approval in this setting. Secondary endpoints include overall survival, PFS as assessed by the investigator, ORR, and duration of response. Nuvation Bio is continuing to evaluate enrollment of grade 2 patients with high-risk features in G203, as these patients currently have very limited options. A trial in progress poster on G203 was presented at the 30th Annual Meeting of the Society for Neuro-Oncology..."

Clinical protocol • Trial status • Glioma

Long-term treatment with mutant IDH inhibitor DS-1001b suppresses tumor growth and induces epigenetic reprogramming in IDH1-mutant gliomas (SNO 2025) - "These findings demonstrated that sustained inhibition of mutant IDH1 with DS-1001b exerted antitumor effects in IDH1-mutant gliomas both in vitro and in vivo, accompanied by changes in transcriptomic and epigenetic profiles."

Astrocytoma • Brain Cancer • CNS Tumor • Glioma • Oligodendroglioma • Oncology • Solid Tumor • IDH1

Nuvation Bio Announces Publication of Positive Phase 2 Study Results for Safusidenib for the Treatment of Grade 2 IDH1-Mutant Glioma in Neuro-Oncology (Businesswire) - "The study met its primary endpoint, demonstrating an objective response rate (ORR) of 44.4%; median duration of response could not be estimated because no progression events had occurred. As of the data cut-off (March 10, 2023), median progression-free survival (PFS) was not yet reached, with a median follow-up time of 28 months, demonstrating the long-term potential of safusidenib to delay disease progression. At 24 months, 87.9% of patients were progression free....'We look forward to sharing longer-term follow-up data in the future'."

P2 data • Glioma

Phase 2, multicenter, randomized clinical study to evaluate the efficacy and safety of safusidenib in patients with high-grade isocitrate dehydrogenase 1 (IDH1)-mutant glioma (SNO 2025) - P=N/A, P2 | "Patients with World Health Organization (WHO) Grade 3 or Grade 4 IDH-mutant astrocytoma represent an unmet need because their disease inevitably progresses after current standard therapy (radiation or chemoradiation followed by adjuvant temozolomide), at which point salvage therapies provide nominal benefit. The primary endpoint for part 2 is progression-free survival by blinded independent central review using RANO 2.0 criteria. Secondary endpoints include objective response rate, duration of response, overall survival, time to next intervention, investigator-assessed progression-free survival, and safety/tolerability."

Clinical • P2 data • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Solid Tumor • IDH1

Long-term treatment with mutant IDH inhibitor DS-1001b suppresses tumor growth and induces epigenetic reprogramming in IDH1-mutant gliomas (WFNOS 2025) - "These findings demonstrated that sustained inhibition of mutant IDH1 with DS-1001b exerted antitumor effects in IDH1-mutant gliomas both in vitro and in vivo, accompanied by changes in transcriptomic and epigenetic profiles."

Astrocytoma • Brain Cancer • Oligodendroglioma • Oncology • Solid Tumor • IDH1

Phase 2, multicenter, randomized clinical study to evaluate the efficacy and safety of safusidenib in patients with high-grade isocitrate dehydrogenase 1 (IDH1)-mutant glioma (WFNOS 2025) - P=N/A, P2 | "Patients with World Health Organization (WHO) Grade 3 or Grade 4 IDH-mutant astrocytoma represent an unmet need because their disease inevitably progresses after current standard therapy (radiation or chemoradiation followed by adjuvant temozolomide), at which point salvage therapies provide nominal benefit. The primary endpoint for part 2 is progression-free survival by blinded independent central review using RANO 2.0 criteria. Secondary endpoints include objective response rate, duration of response, overall survival, time to next intervention, investigator-assessed progression-free survival, and safety/tolerability."

Clinical • P2 data • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Solid Tumor • IDH1

Characterizing Secondary-Site Mutations in Isocitrate-Dehydrogenase-1 (IDH1) (ASH 2024) - "The inhibitors investigated include ivosidenib (AG120), IDH889, IDH305, DS-1001b, GSK864, BAY1436032, olutasidenib (FT-2102), and vorasidenib (AG881), some of which either are in clinical trials or are FDA-approved. Conclusion Second-site mutants of mIDH1 exhibit different leukemogenic properties and differentiation potential in vivo, and show distinct patterns of resistance and sensitivity to ivosidenib, olutasidenib and other mIDH1 inhibitors. Our study provides a rationale to choose an IDH1 inhibitor in patients with secondary site IDH1 mutations."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • HOXA9 • IDH1 • ITGAM

Phase II study of safusidenib erbumine in patients with chemotherapy- and radiotherapy-naïve isocitrate dehydrogenase 1-mutated WHO grade 2 gliomas. (PubMed, Neuro Oncol) - P2 | "Safusidenib erbumine is a potential treatment option for patients with chemotherapy- and radiotherapy-naïve IDH1-mutated WHO grade 2 gliomas."

Journal • P2 data • Alopecia • Brain Cancer • Glioma • Immunology • Musculoskeletal Pain • Oncology • Solid Tumor • IDH1

Nuvation Bio Inc…announced enrollment of the first patient into part 2 of G203 (NCT05303519), a global, randomized study evaluating the efficacy and safety of safusidenib versus placebo for the maintenance treatment of patients with high-grade IDH1-mutant astrocytoma following standard-of-care radiation or chemoradiation and adjuvant temozolomide. (Businesswire) - "A protocol amendment is in progress to finalize G203 as a global Phase 3 study by increasing the study size to support potential regulatory approvals. Based on this amendment, which has been aligned on with the U.S. Food and Drug Administration (FDA), G203 part 2 is now enrolling approximately 300 patients with newly diagnosed IDH1-mutant astrocytoma—either grade 3 with high-risk features or grade 4—in the U.S., Australia, and China...Nuvation Bio will provide further updates on the progress of the safusidenib program in the upcoming earnings call on November 3, 2025."

Clinical protocol • Trial status • Astrocytoma

Targeting of Mutant Isocitrate Dehydrogenase in Glioma: A Systematic Review. (PubMed, Cancers (Basel)) - "The presence of contrast enhancement is consistently a negative predictor of response for ivosidenib and vorasidenib, although safusidenib and olutasidenib preliminarily may retain efficacy in these cases. Mutant IDH inhibition is a promising, well-tolerated, and evolving approach for many patients with IDH-mutant glioma. Ongoing research will clarify its optimal clinical utility and potentially expand its indication."

IO biomarker • Journal • Review • Brain Cancer • Glioma • Oncology • Solid Tumor

Second Quarter 2025 and Recent Corporate Highlights (Businesswire) - "Discussions with the FDA regarding registration-enabling trials of safusidenib are ongoing, and the Company plans to provide additional updates in the second half of 2025...The Company expects to provide an update from the Phase 1/2 dose escalation study of NUV-1511 in the second half of 2025....To date, our only source of product revenue has been from the U.S. sales of IBTROZI. We began shipping IBTROZI to our U.S. customers in June 2025. Product revenue, net from U.S. sales of IBTROZI was approximately $1.2 million for the three months ended June 30, 2025."

New trial • Sales • Trial status • Glioma • Non Small Cell Lung Cancer

Safusidenib Phase 2 Study in IDH1 Mutant Glioma (clinicaltrials.gov) - P2 | N=125 | Recruiting | Sponsor: Nuvation Bio Inc. | Active, not recruiting ➔ Recruiting

Enrollment open • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • IDH1

Establishment and characterization of TK-DDCS1: a novel IDH1 mutated dedifferentiated chondrosarcoma cell line. (PubMed, Hum Cell) - "The mutant IDH1 inhibitor, DS-1001b, inhibited the proliferation of TK-DDCS1 in a dose-dependent manner in both two-dimensional and spheroid cultures. The tumorigenicity of TK-DDCS1 was demonstrated through xenografting into EGFP-transgenic BALB/c Rag2-/-/Jak3-/- (EGFP-BRJ) mice, where the tumors exhibited undifferentiated phenotypes of DDCS in both morphological and immunohistochemical features. Thus, TK-DDCS1 serves as a valuable model for investigating the characteristics of DDCS and exploring molecular targeted therapies."

Journal • Preclinical • Oncology • Sarcoma • Solid Tumor • IDH1 • JAK3

Safusidenib Phase 2 Study in IDH1 Mutant Glioma (clinicaltrials.gov) - P2 | N=125 | Active, not recruiting | Sponsor: Nuvation Bio Inc. | N=95 ➔ 125 | Trial completion date: Jul 2027 ➔ Mar 2028 | Trial primary completion date: Mar 2027 ➔ Dec 2027

Enrollment change • Trial completion date • Trial primary completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • IDH1

Nuvation Bio Reports First Quarter 2025 Financial Results and Provides Business Update (Businesswire) - "Recent Pipeline Updates: (i) Taletrectinib, ROS1 inhibitor: Advanced ROS1+ NSCLC: The Priority Review of the Company’s NDA for taletrectinib for advanced ROS1+ NSCLC (line agnostic, full approval) is progressing on time with all planned inspections now completed. The PDUFA goal date of June 23, 2025, positions Nuvation Bio to commercialize taletrectinib in the U.S., if approved, in mid-2025...; (ii) Safusidenib, mIDH1 inhibitor: Diffuse IDH1-mutant glioma: The Company expects to provide an update on the pivotal study design for the safusidenib program in the second half of 2025; (iii) NUV-1511, drug-drug conjugate (DDC): Advanced solid tumors: The Company expects to provide an update from the Phase 1/2 dose escalation study of NUV-1511 in the second half of 2025."

Clinical protocol • Launch • P1/2 data • PDUFA • Glioma • Non Small Cell Lung Cancer

Study of DS-1001b in Patients With Gene IDH1-Mutated Gliomas (clinicaltrials.gov) - P=N/A | N=47 | Active, not recruiting | Sponsor: Daiichi Sankyo | Trial completion date: Mar 2026 ➔ Aug 2026

Trial completion date • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • IDH1

Perioperative clinical trial reveals decreased synaptic signaling and restoration of metabolism as mechanisms of mutant IDH inhibition (LCC 2025) - " In the first pre- and post-treatment perioperative trial in patients with mIDH1 low-grade glioma, we tested safusidenib (AB-218 / DS-1001b), an oral, blood brain barrier penetrant IDH1 R132X inhibitor, in a single-arm, open-label study... Taken together, these results provide detailed understanding on mechanism of mIDH inhibition for glioma, and a proof of concept of the perioperative approach to advance drug development in glioma."

Clinical • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • IDH1

Safusidenib Phase 2 Study in IDH1 Mutant Glioma (clinicaltrials.gov) - P2 | N=95 | Active, not recruiting | Sponsor: Nuvation Bio Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • IDH1