Preliminary results from the first in human study of activin-A inhibitor, STM434, in patients with granulosa cell ovarian cancer and other advanced solid tumors.

5536 Background: STM 434 is an ACVR2B soluble receptor ligand trap that inhibits activin-A, a protein in the TGF-beta superfamily implicated in tumor growth, angiogenesis and immune modulation. Mutant FOXL2 drives activin A signaling and is present in ~97% of adult-type granulosa cell tumors. Methods: Using a 3+3 dose escalation design, the safety and pharmacokinetics (PK) of STM 434 IV every 2-4 weeks was evaluated. All patients (pts) continued until disease progression or unacceptable toxicity. CT scans were performed every 8-12 weeks. Results: We report interim January 2016 data in 22 pts who received STM 434 at doses of 0.25, 0.5, 0.75, and 1 mg/kg. Tumor types included ovarian cancer (n = 14; 9 granulosa cell, 3 serous, and 2 clear cell), colon (n = 2), and other solid tumors (n = 6). The most common treatment-emergent adverse events (AEs) were fatigue (n = 8), abdominal pain (n = 6), headache (n = 4), rash (n = 4), and epistaxis (n = 4); AEs were generally Grade 1-2. One DLT of self-limited peritoneal bleeding in a patient with clear cell ovarian cancer and peritoneal metastases was observed at the 0.5 mg/kg dose. At 0.75 mg/kg Grade 1 spider angioma was observed in one pt. The mean T1/2 was 5-7 days, and PK was linear between 0.25 mg/kg and 1 mg/kg. STM 434 administration resulted in the expected pharmacodynamic response to activin A inhibition with follicle stimulating hormone levels decreasing in a majority of patients. Stable disease (SD) up to 7 months in duration has been observed in 5/22 (23%) of pts including four granulosa cell tumor pts. The pt with spider angioma, who had a granulosa cell tumor, had a 20% reduction in tumor linear diameter. The SD rate in granulosa tumors was 4/9 (44%). Conclusions: Single agent STM 434 showed an acceptable safety profile in patients with advanced solid tumors and early evidence of clinical activity, particularly in patients with granulosa cell ovarian cancer. The MTD has not been determined and dose escalation is ongoing to determine the recommended phase 2 dose. Clinical trial information: NCT02262455.