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 Journal Article
| Authors: | Tao, J. J.; Cangemi, N. A.; Makker, V.; Cadoo, K. A.; Liu, J. F.; Rasco, D. W.; Navarro, W. H.; Haqq, C. M.; Hyman, D. M. |
| Article Title: | 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 |
| Abstract: | Purpose: STM 434 is a soluble receptor ligand trap targeting activin A, a protein in the TGFβ family that plays important roles in growth, differentiation, and cancer cachexia. This study evaluated the safety, antitumor activity, and metabolic effects of STM 434 in a first-in-human, multicenter, phase I clinical trial (NCT02262455). Patients and Methods: Patients with advanced solid tumors were enrolled in 8 dose cohorts ranging from 0.25 mg/kg every 4 weeks to 8 mg/kg every 2 weeks via a 3 + 3 dose-escalation design. The primary endpoint was maximum tolerated dose (MTD). Secondary endpoints included safety, pharmacokinetics, and response. As activin A is implicated in metabolism and muscle function, changes in keymetabolic parameters, including lean body mass and 6-minute walk test, were serially measured. Results: Thirty-two patients were treated on study. The most common treatment-related adverse events were fatigue (41%) and mucocutaneous bleeding complications including epistaxis (34%) and gingival bleeding (22%), likely related to off-target inhibition of bone morphogenetic protein 9 (BMP9). STM 434 treatment resulted in the expected follicle- stimulating hormone level decreases in most patients and in metabolic parameter changes, including an increase in total lean body mass and 6-minute walk test distance. No responses were observed in the 30 evaluable patients, but the stable disease rate in patients with granulosa cell ovarian cancer was 10 of 12 (80%). Conclusions: 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. © 2019 American Association for Cancer Research. |
| Journal Title: | Clinical Cancer Research |
| Volume: | 25 |
| Issue: | 18 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2019-09-15 |
| Start Page: | 5458 |
| End Page: | 5465 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-19-1065 |
| PUBMED: | 31068369 |
| PROVIDER: | scopus |
| PMCID: | PMC7899078 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2019 -- Source: Scopus |
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