Background: In platinum-resistant ovarian cancer, the monoclonal antibody P, which inhibits HER2 heterodimerization, improved PFS when added to gemcitabine in the subgroup of pts with low tumor HER3 mRNA expression [Makhija, 2010]. The 2-part PENELOPE trial (NCT01684878) is prospectively investigating P added to single-agent CT in this population. Methods: Part 1 (safety run-in) of PENELOPE evaluated P + either topotecan (TOP) or paclitaxel (PAC). Pts with platinum-refractory or -resistant recurrent ovarian, primary peritoneal, or fallopian tube cancer (progression [PD] during or within 6 mo of completing ≥4 platinum cycles) and low HER3 mRNA expression (concentration ratio ≤2.81 by central qRT-PCR testing on cobas z480) received IV P 840→420 mg q3w + investigator’s choice of TOP (1.25 mg/m² d1–5 q3w; cohort 1) or PAC (80 mg/m² d1, 8, 15 q3w; cohort 2) until PD or unacceptable toxicity. The primary objective was to assess safety and tolerability. After all pts had received ≥3 cycles, the Independent Data Monitoring Committee (IDMC) assessed safety results to recommend which regimen(s) should be included in Part 2. Results: InPart 1, 50 pts were enrolled and treated between Oct 2012 and Jul 2013. At data cut-off (Aug 27, 2013), 8 TOP and 17 PAC pts remained on treatment. Conclusions: Both regimens were tolerable. Based on these results, the IDMC had no objection to the trial proceeding to Part 2 (double-blind randomized comparison of CT [TOP, PAC, or gemcitabine] + P or placebo). Clinical trial information: NCT01684878.

^aInfection. ^b1 further pt discontinued P (grade 1 hypersensitivity). ^cMedDRA preferred terms in >10%.