Elevation Oncology is axing development of its Claudin 18.2 ADC EO-3021 in Phase 1

DEALS AND FINANCING

Genmab announced updated data from cohort B1 of the Phase 1/2 RAINFOL-01 study of rinatabart sesutecan (Rina-S), an investigational FRα-targeted, TOPO1 ADC that showed Rina-S 120 mg/m2 every 3 weeks (Q3W) resulted in a confirmed ORR of 55.6% (95% CI: 30.8-78.5) in heavily pre-treated ovarian cancer (OC) patients regardless of FRα expression levels. With a median on-study follow-up of 48 weeks, 1 out of 10 patients experienced disease progression and the median DOR was not reached (95% CI: 40.14-NR). The data are from the dose expansion cohort of the multi-part study evaluating the safety and efficacy of Rina-S as a single agent in solid tumors that are known to express FRα and were presented at the 2025 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer. In this Phase 1/2 study, common treatment-emergent adverse events included anemia, nausea, neutropenia, leukopenia, fatigue, thrombocytopenia, vomiting, diarrhea, alopecia, and hypokalemia. Dose reductions and treatment discontinuations were infrequent and no new safety signals were observed.

Sutro presented data from dose-optimization portion of REFRαME-O1 trial in ovarian cancer

Sutro announced expanded data in a late-breaking oral presentation from the dose-optimization portion of the REFRαME-O1 trial with luveltamab tazevibulin (luvelta) in patients with platinum resistant ovarian cancer (PROC) at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer. In this study, luvelta demonstrated encouraging antitumor activity in patients with late-stage ovarian cancer across all levels of FRα expression of 25% or greater, including an improved ORR, a low discontinuation rate, and a consistent safety profile across dose levels. Based on these findings, Sutro selected the optimized dose of luvelta: 5.2 mg/kg + G-CSF for two cycles then continued on 4.3 mg/kg. At the selected optimized dose (5.2 mg/kg), luvelta achieved an ORR of 32%1 and a DCR of 96% compared to an ORR of 13.8% and a DCR of 69% for the 4.3 mg/kg group. The demonstrated clinical activity in the 5.2 mg/kg group was consistent in patients across all levels of FRαexpression of 25% or greater, with an ORR of 30.8% and a DCR of 100% for positive staining (PS) 2+ ≥75% (eligible for approved FRα-targeting ADC) and an ORR of 33.3%1 and DCR of 91.7%1 for PS2+ < 75%.

Elevation Oncology to discontinue development of EO-3021 

Elevation Oncology announced that it has elected to discontinue development of EO-3021. EO-3021 is a Claudin 18.2 ADC, which Elevation was developing for the treatment of advanced, unresectable or metastatic gastric and gastroesophageal junction (GEJ) cancers. The decision to discontinue clinical development of EO-3021 was based on data from the dose escalation and expansion stages of Elevation Oncology's Phase 1 trial, in which treatment with EO-3021 as a monotherapy demonstrated an ORR of 22.2% (95% CI: 10, 39; 1 confirmed complete response and 7 confirmed partial responses) and a disease control rate (DCR) of 72.2% (95% CI: 55, 86) among 36 evaluable patients with gastric or GEJ cancer and Claudin 18.2 in ≥20% of tumor cells at IHC 2+/3+. In the safety analysis of all enrolled patients (n=85), treatment with EO-3021 was observed to be generally well-tolerated, with an adverse event profile consistent with previously reported data, including minimal hematological toxicity and hepatotoxicity, and no peripheral neuropathy/hypoesthesia.

MacroGenics axes its ADC following Phase 2 failure in prostate cancer

MacroGenics announced it will discontinue the development of one of its ADC after it flopped in a Phase 2 study in prostate cancer. Vobramitamab duocarmazine (vobra duo) is an ADC with a cleavable peptide linker designed to deliver a DNA-alkylating duocarmycin payload to solid tumors that express B7-H3. Results for the concluded TAMARACK Phase 2 study included, based on a February 21, 2025 data cut-off, mature median radiographic PFS of 9.5 months for the 2.0 mg/kg cohort (95% CI, 8.5-11.2) and 10.0 months for the 2.7 mg/kg cohort (95% CI, 7.4-11.4) in patients with mCRPC. Safety data from the study remained consistent with prior data disclosures. Based on its assessment of the vobra duo safety and efficacy profile and an internal resource and portfolio review, MacroGenics has decided not to pursue further internal development of vobra duo and will instead explore potential alternatives for partnering this program.