STM-434 / Atara - LARVOL DELTA

Livmoniplimab and budigalimab combination therapy in treating patients with metastatic ovarian granulosa cell tumors: results from dose escalation in a first-in-human study (AIOM 2024) - P1 | "Several agents with different targets, such as pembrolizumab, nirogacestat, orteronel and STM 434, are being evaluated but to date without clinical benefit...She had received 7 prior lines of therapy including doxorubicin, bevacizumab, anastrozole, tamoxifen and carboplatin+paclitaxel... Livmo+budi had promising antitumor efficacy and tolerablesafety profile in pts with metastatic OGC. All enrolled pts showed tumor shrinkage and 1 pt had durable and near-complete response. Since singleagent pembrolizumab exhibited an ORR of 0%(How et al."

Clinical • Combination therapy • Metastases • P1 data • Anemia • Fatigue • Hematological Disorders • Hepatology • Oncology • Ovarian Cancer • Solid Tumor • FOXL2 • TGFB1

Livmoniplimab and budigalimab combination therapy in treating patients with metastatic ovarian granulosa cell tumors: Results from dose escalation in a first-in-human study (AACR 2024) - P1 | "Several agents with different targets, such as pembrolizumab, nirogacestat, orteronel, and STM 434, are being evaluated but to date have not shown clinical benefit...She had received 7 prior lines of therapy including doxorubicin, bevacizumab, anastrozole, tamoxifen, and carboplatin + paclitaxel... Livmo + budi had promising antitumor efficacy and a tolerable safety profile in pts with metastatic OGC, a rare TGF-β signaling-dependent tumor. All enrolled pts with OGC showed tumor shrinkage and 1 pt had durable and near-complete response. Since single-agent pembrolizumab exhibited an ORR of 0% in pts with OGC (How et al."

Clinical • Combination therapy • IO biomarker • Metastases • P1 data • Oncology • Ovarian Cancer • FOXL2 • TGFB1

First in human study of activin-A inhibitor, STM434, in patients with granulosa cell ovarian cancer and other advanced solid tumors (AACR 2018) - "The MTD of STM434 was 4 mg/kg Q2W. STM434 use resulted in mucocutaneous bleeding complications likely related to off-target inhibition of bone morphogenic protein 9 (BMP9). BMP9 bears substantial homology to activin A and inherited inactivation of BMP9 can result in hereditary hemorrhagic telangiectasia which shares a phenotype similar to the AE profile observed here."

Clinical • P1 data • Hematological Malignancies • Ovarian Cancer

First-in-Human Phase I Study of the Activin A Inhibitor, STM 434, in Patients with Granulosa Cell Ovarian Cancer and Other Advanced Solid Tumors. (PubMed, Clin Cancer Res) - P1; "Although no direct antitumor efficacy was documented, potentially clinically meaningful dose-related metabolic effects, including treatment of cancer cachexia, were observed that support further exploration of activin A inhibitors that limit BMP9 blockade.See related commentary by Bonilla and Oza, p. 5432."

Clinical • Journal • P1 data