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

Disentangling disease from drug: neurological adverse events with IDH inhibitors in glioma (EANO 2026) - "Extracted outcomes focused on the incidence, severity, and characterization of neurological adverse events, with particular attention to reporting methodology and attribution. Across phase I-III trials of IDH inhibitors—including vorasidenib, ivosidenib, olutasidenib, and safusidenib—neurological adverse events were commonly reported, with headache being the most frequent (approximately 13-46%). The interpretation of neurological adverse events in IDH-mutant gliomas is limited by significant methodological heterogeneity, lack of standardized symptom reporting, and confounding from tumor-related manifestations and prior therapies. Neurological adverse events in IDH inhibitor-treated glioma patients are common but undercharacterized. Available evidence suggests that some symptoms-particularly headache-may reflect the underlying disease rather than drug toxicity, at least in certain contexts."

Adverse events • Brain Cancer • Glioma • Oncology • Solid Tumor

SAFU-G3: Safusidenib for Patients With Newly Diagnosed IDH1-mutant CNS WHO Grade 3 Oligodendroglioma and Astrocytoma - a Single Arm Phase II Study (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: University of Zurich

New P2 trial • Astrocytoma • Brain Cancer • Glioma • Oligodendroglioma • Oncology • Solid Tumor • IDH1

SIGMA: A Phase 3 study evaluating maintenance safusidenib vs placebo following radiotherapy (RT) or chemoradiotherapy (CRT) and adjuvant temozolomide (TMZ) in patients with isocitrate dehydrogenase 1 (IDH1)-mutant astrocytoma with high-risk features (SNO 2026) - No abstract available

Clinical • P3 data • Astrocytoma • Brain Cancer • Oncology • Solid Tumor • IDH1

Open-label, single-arm, exploratory cohort evaluating safusidenib in chemotherapy (CT)- and radiotherapy (RT)-naïve patients with Grade 3 isocitrate dehydrogenase 1 (IDH1)-mutant oligodendroglioma (SNO 2026) - No abstract available

Clinical • Brain Cancer • Glioma • Oligodendroglioma • Solid Tumor • IDH1

Updated efficacy and safety results from a Phase 2 study of safusidenib in patients with chemotherapy- and radiotherapy-naïve Grade 2 isocitrate dehydrogenase 1 (IDH1)-mutant glioma (SNO 2026) - No abstract available

Clinical • P2 data • Brain Cancer • Glioma • Solid Tumor • IDH1

A Phase 2 study evaluating the efficacy and safety of safusidenib in Grade 2 or 3 isocitrate dehydrogenase 1 (IDH1)-mutant glioma after disease progression (PD) on vorasidenib (SNO 2026) - No abstract available

Clinical • P2 data • Brain Cancer • Glioma • Solid Tumor • 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

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

Nuvation Bio Granted FDA Fast Track Designation for Safusidenib for Treatment of IDH1-Mutant Glioma (PRNewswire) - "The designation was granted based on favorable data from the safusidenib clinical program to date....Pivotal Phase 3 SIGMA study enrollment underway."

Fast track • Trial status • Glioma

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

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

Expanding the safusidenib clinical development program (Investing News Network (INN)) - "G307: A Phase 3, randomized, placebo-controlled study that will enroll approximately 140 patients with newly diagnosed grade 2 IDH1-mutant glioma who have not yet received chemotherapy or radiation. The study will be conducted at sites outside the U.S. in regions where vorasidenib is not yet approved or accessible, providing this clinical trial as a critical option for patients in need in these regions. The primary endpoint is PFS as assessed by blinded independent central review (BICR). Secondary endpoints include ORR, time to next intervention, duration of response, and time to response....G209: A Phase 2, multicenter study that will enroll up to 40 patients in the U.S. with grade 2 or 3 IDH1-mutant glioma who have experienced disease progression after treatment with vorasidenib and who remain in need of another option to delay radiation or chemotherapy."

Trial status • Astrocytoma • Glioma • Oligodendroglioma

Updated long-term data highlights durable efficacy (Investing News Network (INN)) - "The updated results from the Phase 2 (J201) study, from 27 patients in Japan, further support this clinical expansion. Highlights of the findings, at a median of 38.8 months of follow-up, include the following: The centrally assessed confirmed overall response rate (ORR), per Response Assessment in Neuro-Oncology (RANO) for low grade gliomas (LGG) criteria, was 51.9%; Median progression-free survival (PFS) was not reached, and the 36-month PFS rate was 79.1%.; Responses were durable, with only one patient who had previously responded experiencing subsequent disease progression; No new safety signals were identified."

P2 data • Glioma

Safety and Efficacy Study of Safusidenib in Participants With Grade 2 IDH1-Mutant Glioma (clinicaltrials.gov) - P3 | N=140 | Not yet recruiting | Sponsor: Nuvation Bio Inc.

New P3 trial • Astrocytoma • Brain Cancer • Glioma • Oligodendroglioma • Oncology • Solid Tumor • IDH1

Safety and Efficacy Study of Safusidenib in Participants With IDH1-Mutant Glioma Who Discontinued Vorasidenib Treatment Due to Progressive Disease (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Nuvation Bio Inc.

New P2 trial • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioma • Oligodendroglioma • Oncology • Solid Tumor • IDH1

Nuvation Bio Announces Acquisition of Japan Rights to Safusidenib from Daiichi Sankyo (PRNewswire) - "Agreement provides Nuvation Bio ownership of global clinical development program, inclusive of clinical trials, past and current data generation, and future publications...The agreement, as amended, enables Nuvation Bio to expand its ongoing pivotal SIGMA study of safusidenib into Japan, and provides rights to all previously generated and future data to support further publication of safusidenib results in IDH1-mutant glioma...Nuvation Bio plans to present longer-term data from the Phase 2 study at a future medical meeting."

P2 data • Trial status • Glioma

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

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