VLS-1488 / Volastra Therap - LARVOL DELTA

Preliminary results from a first-in-human, phase I/II study of VLS-1488, an oral KIF18A inhibitor, in patients with advanced solid tumors. (ASCO 2025) - P1/2 | "VLS-1488 was found to be safe and tolerable, with encouraging anti-tumor activity observed in heavily treated HGSOC pts. VLS-1488 will be evaluated further in the Dose Expansion phase of the study. Clinical trial information: NCT05902988."

Clinical • Metastases • P1/2 data • Carcinosarcoma • Fatigue • Oncology • Sarcoma • Solid Tumor • Triple Negative Breast Cancer • KIF18A

Combination of VLS-1488 and taxanes induces anti-tumor synergistic effect in cancer cells (AACR 2026) - "In vivo, xenograft studies using ovarian cancer cells resistant to VLS-1488 and paclitaxel single agent treatment, demonstrated that combination treatment of VLS-1488 and paclitaxel results in a synergistic anti-tumor activity, total prevention of tumor growth, and no significant loss in body weight. We hypothesize that combination treatment of VLS-1488 and taxanes in cancer cells prolongs mitotic arrest and prevents mitotic slippage to an extent that induces cell death. Overall, our findings presented suggest that combination treatment of VLS-1488 and taxanes may offer benefit to patients with limited or no response to VLS-1488 monotherapy and/or taxanes."

Breast Cancer • High Grade Serous Ovarian Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • KIF18A

AACR Poster Highlights Clear Synergy with Taxanes and Other Microtubule-Targeting Agents (PharmiWeb) - "The presentation will highlight preclinical combination data showing clear synergistic activity between KIF18A inhibition and taxanes and other microtubule-targeting agents. These findings support a development strategy that could extend KIF18A inhibitors into earlier lines of therapy, including combination approaches in frontline settings."

Preclinical • Solid Tumor

Volastra Therapeutics Announces Biomarker and Combination Data around AACR 2026 Defining an Rb Pathway-Driven Pan-Cancer Development Strategy for KIF18A Inhibitors (PharmiWeb) - "The study includes clinical data from a substantial cohort of 79 heavily pretreated patients with high-grade serous ovarian cancer treated with either of two distinct KIF18A inhibitors, sovilnesib and VLS-1488. The concordance of the biomarker-defined signal across both agents is particularly compelling and argues against a drug-specific observation. Biomarker-positive tumors were distinguished by marked enrichment for objective responses, durable disease control, and longer progression-free survival, yielding a sharp clinical separation from biomarker-negative disease and strongly supporting both the biomarker strategy and prospective clinical development."

Biomarker • Clinical data • High Grade Serous Ovarian Cancer

KIF18A inhibition and its rising role in cancer therapy trials: from bench to bedside. (PubMed, Expert Opin Investig Drugs) - "We summarize the development of small-molecule inhibitors, from early compounds like BTB-1 to second-generation agents including Sovilnesib and VLS-1488, the latter currently in Phase I/II trials...New entrants like ATX-295 and GH2616 further expand the landscape...As clinical trials progress, optimizing patient stratification and exploring synergistic combinations will be crucial. Broadening the range of druggable sites on KIF18A, especially beyond the motor domain, could mitigate resistance and help expand therapeutic potential."

Journal • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • KIF18A

A Phase I/II Study of VLS-1488 in Subjects With Advanced Cancer (clinicaltrials.gov) - P1/2 | N=200 | Recruiting | Sponsor: Volastra Therapeutics, Inc. | N=120 ➔ 200

Enrollment change • Breast Cancer • Carcinosarcoma • Endometrial Cancer • Endometrial Serous Adenocarcinoma • Head and Neck Cancer • High Grade Serous Ovarian Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Uterine Cancer • CTCs

A Phase I/II Study of VLS-1488 in Subjects With Advanced Cancer (clinicaltrials.gov) - P1/2 | N=120 | Recruiting | Sponsor: Volastra Therapeutics, Inc. | Trial completion date: Jun 2026 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Breast Cancer • Carcinosarcoma • Endometrial Cancer • Endometrial Serous Adenocarcinoma • Head and Neck Cancer • High Grade Serous Ovarian Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Uterine Cancer • CTCs

Volastra Announces Initial Data from First-in-Human Phase I/II Trial of Novel KIF18A Inhibitor VLS-1488 to be Presented at 2025 ASCO Annual Meeting (Businesswire) - P1/2 | N=120 | NCT05902988 | Sponsor: Volastra Therapeutics, Inc. | "As of the January 10, 2025 data cutoff, 52 patients with advanced solid tumors were enrolled to the dose escalation portion of the trial across dose levels ranging from 50 mg to 800 mg. Drug exposures exceeded preclinically-defined efficacious thresholds for anti-tumor activity. No dose limiting toxicities were observed and a maximum tolerated dose was not reached. Less than 45% of patients experienced treatment-related adverse events (TRAEs) of any grade and less than 16% of all patients experienced G3 TRAEs. No patients experienced >G3 TRAEs. Of the 20 patients with advanced high grade serous ovarian cancer, the majority were platinum resistant and heavily pretreated with a median of 5 prior lines of therapy."

P1/2 data • Platinum resistant • High Grade Serous Ovarian Cancer

Volastra Therapeutics Granted FDA Fast Track Designation for Novel KIF18A Inhibitor in Ovarian Cancer (Businesswire) - "Volastra Therapeutics...announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to VLS-1488, the company’s internally discovered KIF18A inhibitor. The designation has been granted for the treatment of patients with platinum-resistant high-grade serous ovarian cancer (HGSOC)....The Phase I/II trial for VLS-1488 is evaluating safety, tolerability and preliminary efficacy in patients with advanced tumors, including HGSOC."

Fast track • Ovarian Cancer

A phase I/II, first-in-human study of VLS-1488, an oral KIF18A inhibitor, in patients with advanced cancer. (ASCO 2024) - P1/2 | "Subjects enrolled to specific tumor type cohorts may be randomized to DLs of interest. Enrollment to Dose Escalation began in September 2023 and is ongoing."

Clinical • Metastases • P1/2 data • Bladder Cancer • Breast Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Endometrial Serous Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • Uterine Cancer • KIF18A

A Phase I/II Study of VLS-1488 in Subjects With Advanced Cancer (clinicaltrials.gov) - P1/2 | N=120 | Recruiting | Sponsor: Volastra Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Bladder Cancer • Breast Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Endometrial Cancer • Endometrial Serous Adenocarcinoma • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • Uterine Cancer • CTCs • MUC16

Volastra Therapeutics Announces First Patient Dosed in Phase I/II Clinical Trial of VLS-1488, One in a Portfolio of Novel and Differentiated KIF18A Inhibitors (Businesswire) - "Volastra Therapeutics...announced the dosing of the first patient in a Phase I/II clinical trial evaluating VLS-1488. VLS-1488 and sovilnesib (formally AMG650) make up Volastra’s innovative clinical portfolio of differentiated KIF18A inhibitors specifically designed for the treatment of solid tumors characterized by high levels of chromosomal instability (CIN). The Phase I/II trial (NCT05902988) evaluates safety, tolerability and preliminary efficacy of VLS-1488 in patients with advanced tumors....Phase Ib trial for sovilnesib, Volastra’s second KIF18A inhibitor, is anticipated to open in Q1 2024."

Trial status • Ovarian Cancer

A Phase I/II Study of VLS-1488 in Subjects With Advanced Cancer (clinicaltrials.gov) - P1/2 | N=120 | Not yet recruiting | Sponsor: Volastra Therapeutics, Inc.

Metastases • New P1/2 trial • Bladder Cancer • Breast Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Endometrial Cancer • Endometrial Serous Adenocarcinoma • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • Uterine Cancer • CTCs • MUC16

Preclinical Data on Volastra Therapeutics’ Two Novel and Differentiated KIF18A Inhibitors Presented at AACR 2023 (Businesswire) - "Volastra Therapeutics...released preclinical data from the company’s portfolio of KIF18A inhibitors at the 2023 American Association for Cancer Research (AACR) Annual Meeting....Sovilnesib findings, presented in a poste...demonstrate robust anti-cancer activity with evidence of durable tumor regressions in a subset of human ovarian and breast tumor models at well-tolerated doses....Findings for one of Volastra’s internally-developed KIF18A inhibitors are shown in a second poster....In this, in vivo data shows substantial, dose-dependent inhibition of tumor growth in multiple tumor models....Volastra will advance clinical development of both sovilnesib and the Volastra-developed KIF18A inhibitor VLS-1488 in 2023."

Clinical • Preclinical • Breast Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Volastra Therapeutics In-Licenses Clinical Stage KIF18A Inhibitor and Secures $60 Million in Series A Funding to Further Advance Cancer-Focused Pipeline (Businesswire) - "Volastra Therapeutics...announced completion of the in-license of Amgen’s sovilnesib (AMG650), an oral, first-in-class small molecule inhibitor of KIF18A. In parallel, the company has closed a $60 million Series A financing. Under the terms of the licensing agreement, Volastra receives an exclusive worldwide license (ex-China) to develop and commercialize sovilnesib. In return, Amgen receives an upfront mix of cash and equity, as well as downstream milestones and royalties. The drug is currently in Phase 1 for the treatment of platinum-resistant high-grade serous ovarian cancer, triple-negative breast cancer and other solid tumors with TP53 mutations....Volastra will advance clinical development of both sovilnesib and VLS-1488 in 2023."

Financing • Licensing / partnership • Pipeline update • Breast Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer