2018 ASCO Annual Meeting!
Session: Developmental Therapeutics—Immunotherapy
Type: Poster Session
Time: Monday June 4, 8:00 AM to 11:30 AM
Location: Hall A
A phase 1/2 study with birinapant in combination with pembrolizumab.
2018 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #330a)
J Clin Oncol 36, 2018 (suppl; abstr TPS3131)
Author(s): Russell J. Schilder, Mark Albertella, James Strauss, Malin Sydvander, Santosh M. Nair, Kingsley Urakpo, Stefan Norin, John Öhd; Thomas Jefferson University Hospital, Philadelphia, PA; Medivir AB, Huddinge, Sweden; Mary Crowley Medical Research Center, Dallas, TX; Mid Florida Hem Onc Ctr, Sanford, FL
Background: Birinapant is a bivalent SMAC mimetic with activity against multiple members of the inhibitor of apoptosis protein (IAP) family including cIAP1 and has demonstrated tolerability with robust and durable target engagement in advanced cancers. Synergistic effects of combining birinapant with immune checkpoint inhibitors have been demonstrated in preclinical models, consistent with the reported role of cIAP1 in tumor cells and immune cells (Beug et al., 2017). Based on these observations, a phase 1/2 trial with birinapant and pembrolizumab has been initiated (NCT02587962). Methods: In the dose escalation part of this multi-center phase 1/2 study, patients > 18 years with advanced solid tumors without further suitable standard therapeutic options are eligible for inclusion. The primary objective is to determine the safety and tolerability of the recommended phase 2 dose (RP2D) of birinapant in combination with pembrolizumab using a standard 3+3 design. The secondary objective is to assess efficacy by RECIST 1.1. The doses of birinapant to be evaluated are 5.6, 11, 17 and 22 mg/m2 IV on day 1 and 8 in addition to pembrolizumab 200 mg on day 1 in a 21-day cycle. RP2D will be proposed by the safety review committee. The phase 2 part plans to include 111 patients. The primary objective is to assess the clinical activity of birinapant and pembrolizumab, measured as ORR by RECIST in separate cohorts of microsatellite stable colorectal (N = 28), ovarian (N = 27) and cervical cancer (N = 26). Simon’s two-stage design yields a type I error rate of 0.05 and statistical power of 0.80 for each of the three cohorts using a one-sided test based on true response rates of 20% (colorectal cancer), 25% (ovarian cancer) and 30% (cervical cancer). The study will also evaluate an exploratory cohort consisting of five patients each with small cell lung cancer, cholangiocarcinoma, gastroesophageal carcinoma, mesothelioma, head and neck squamous cell carcinoma (check-point inhibitor-naïve and experienced). The phase 2 secondary objectives are safety and tolerability, tumor response, progression-free and overall survival. Exploratory objectives will assess tumor response by iRECIST, pharmacokinetics, pharmacodynamics and predictive biomarkers. Clinical trial information: NCT02587962