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

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

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

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

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

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

A perioperative study of Safusidenib in Patients with IDH1 mutated glioma (SNO 2024) - "This innovative trial facilitates intra-patient comparisons and confirmation of the on-target effects of Safusidenib, enhancing understanding of the mechanisms of response and resistance. The approach serves as a proof of concept for advancing drug development in glioma through perioperative trials."

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

IDH1 Inhibitor AB-218 in Patients With Advanced IDH1 Mutant Cholangiocarcinoma and Other Solid Tumor (clinicaltrials.gov) - P1 | N=9 | Terminated | Sponsor: AnHeart Therapeutics Inc. | N=63 ➔ 9 | Trial completion date: May 2026 ➔ Aug 2024 | Recruiting ➔ Terminated | Trial primary completion date: Aug 2025 ➔ Aug 2024; Sponsor adjusted the study strategy

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • 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

A perioperative study of Safusidenib in patients with IDH1-mutated glioma. (PubMed, Future Oncol) - P1 | "This research will enable objective measurement of biological activity of safusidenib in patients with IDH1 mutated glioma. Anti-tumor activity will be assessed by progression free survival and time to next intervention.Clinical Trial Registration: NCT05577416 (ClinicalTrials.gov)."

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

AB-218-IIT-201: A Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma (clinicaltrials.gov) - P1 | N=15 | Recruiting | Sponsor: Melbourne Health | Active, not recruiting ➔ Recruiting | N=10 ➔ 15

Enrollment change • Enrollment open • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

First report of the chromosomal integration of carbapenemase gene blaIMP-19 in Acinetobacter baumannii AB322: the legacy of integron in phage-plasmid? (PubMed, Microbiol Spectr) - "Nanopore whole-genome sequencing platform was utilized for AB322 genome sequencing, and conjugation was further performed to investigate the transferability of blaIMP-19 to amikacin-resistant A. baumannii 218 (AB218) and Acinetobacter nosocomialis 254 (AN254). The results showed that AB322 was classified as multidrug-resistant A. baumannii but remained susceptible to ampicillin/sulbactam, colistin, and tigecycline...AB322 chromosome harbored numerous acquired antimicrobial resistance genes, including aph(3')-Ia, aadA1b, aadA1, aac(6')-Ib3, aac (3)-Ia, blaADC-25, blaOXA-69, blaIMP-19, catA1, sul1, and tet(A), conferring resistance to β-lactams, aminoglycosides, chloramphenicol, sulfamethoxazole, and tetracyclines...However, in this study, we first report the integration of the blaIMP-19 gene into the chromosome of A. baumannii, and such horizontal transfer may be associated with integron-phage elements. Additionally, it is possible that these DNA fragments..."

Journal

AB-218-IIT-201: A Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: Melbourne Health | Recruiting ➔ Active, not recruiting

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

Nuvation Bio to Acquire AnHeart Therapeutics in All-Stock Transaction (Businesswire) - "Acquisition adds taletrectinib, a next-generation, potentially best-in-class ROS1 inhibitor with Breakthrough Therapy Designations currently completing two pivotal studies for the treatment of patients with ROS1-positive non-small cell lung cancer (NSCLC); Acquisition also adds safusidenib, a potentially best-in-class mutant IDH1 inhibitor currently being evaluated in a global Phase 2 study of patients with grades 2 and 3 IDH1-mutant glioma...Nuvation Bio Inc...and AnHeart Therapeutics Ltd. (AnHeart)...announced that the companies have entered into a definitive agreement for Nuvation Bio to acquire AnHeart in an all-stock transaction (the Acquisition). Immediately following the closing of the Acquisition, the former shareholders of AnHeart will own approximately 33% and the current stockholders of Nuvation Bio will own approximately 67% of Nuvation Bio on a fully diluted basis....The Acquisition is expected to close in the second quarter of 2024."

M&A • Brain Cancer • CNS Tumor • Glioma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A 19-year longitudinal study to characterize carbapenem-nonsusceptible Acinetobacter isolated from patients with bloodstream infections and the contribution of conjugative plasmids to carbapenem resistance and virulence. (PubMed, J Microbiol Immunol Infect) - "Our 19-year longitudinal study revealed a stable increase in CNSA during 2005-2015. blaOXA-24-like, ISAba1-blaOXA-51-like, and ISAba1-blaOXA-23 were the major determinants of Acinetobacter carbapenem resistance. MBL-carrying plasmids contribute not only to the carbapenem resistance but also to A. baumannii virulence."

Journal • Observational data • Infectious Disease

A Study of DS-1001b in Patients With Chemotherapy- and Radiotherapy-Naive IDH1 Mutated WHO Grade II Glioma (clinicaltrials.gov) - P2 | N=25 | Active, not recruiting | Sponsor: Daiichi Sankyo Co., Ltd. | Trial primary completion date: Sep 2023 ➔ Mar 2023

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

IDH1 Inhibitor AB-218 in Patients With Advanced IDH1 Mutant Cholangiocarcinoma and Other Solid Tumor (clinicaltrials.gov) - P1 | N=63 | Recruiting | Sponsor: AnHeart Therapeutics Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • IDH1

AnHeart Therapeutics Announces Initiation of Global Phase 2 Trial Evaluating Safusidenib for IDH1-Mutant Glioma (Businesswire) - "AnHeart Therapeutics...today announced the first patient has been dosed in a Phase 2 clinical trial, G203, evaluating safusidenib in patients with Grades 2 or 3 recurrent or progressive mutant isocitrate dehydrogenase 1 (mIDH1) glioma, one of the most common types of adult primary brain cancer."

Trial status • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

A Study of DS-1001b in Patients With Chemotherapy- and Radiotherapy-Naive IDH1 Mutated WHO Grade II Glioma (clinicaltrials.gov) - P2 | N=25 | Active, not recruiting | Sponsor: Daiichi Sankyo Co., Ltd. | Trial primary completion date: Jun 2023 ➔ Sep 2023

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