Date: 2018-10-04
Type of
information: Interim results
phase: 1-2
Announcement: interim results
Company: Medivir (Sweden)
Product: birinapant and pembrozilumab
Action
mechanism:
- IAP (inhibitor of apoptosis protein) inhibitor/SMAC mimetic/monoclonal antibody/immune checkpoint inhibitor.
- Birinapant is a parenterally administered bivalent peptidomimetic of the SMAC protein (Second
Mitochondria-derived Activator of Caspases).
It binds to and degrades inhibitors of apoptosis proteins (IAPs), which both enables apoptosis in tumour cells, and activates the immune system, enhancing its attack on the
tumour.
- Pembrolizumab is a monoclonal anti-PD-1 antibody designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein. By blocking PD-1, this antibody enables activation of the immune system’s T-cells that target cancer by essentially releasing a brake on the immune system.
Disease: treatment-resistant solid tumours
Therapeutic
area: Cancer - Oncology
Country: USA
Trial
details:
- An ascending dose study in patients with solid tumors to evaluate the safety, tolerability, pharmacodynamics and efficacy of birinapant when given in combination with pembrolizumab. A dose expansion phase of 4 cohorts will also be included.
- Under the terms of the agreement between Medivir and Merck & Co, Merck & Co will provide pembrolizumab for this study at no cost to Medivir. Medivir retains full rights to birinapant. (NCT02587962)
Latest
news:
- • On October 4, 2018, Medivir announced safety and efficacy data following an interim analysis of phase I data from the ongoing phase I/II study of birinapant in combination with pembrolizumab, in patients with advanced solid tumors who have exhausted available treatment options.
- No dose-limiting toxicity has been observed in the first three groups of patients, and the dose escalation has been continued to the highest planned dose level in the study. One of the 12 patients in this interim analysis has had a confirmed partial response to treatment, which means that the dimensions of their tumor were reduced by 30% or more on two consecutive assessments approximately two months apart when compared to the size of the tumor when treatment started.
- In the phase I portion of the trial, three groups of 3-6 patients with advanced solid tumors have been fully recruited so far. Each group has received Keytruda® and one of the following doses of birinapant: 5.6mg/m2, 11mg/m2, 17mg/m2. The interim analysis is based on the safety and response data from the 12 patients in these three groups. The data from the current interim analysis show that the safety profile of birinapant in combination with Keytruda® is consistent with the published clinical safety profiles of Keytruda® and birinapant when used as single agents at equivalent doses. No cases of cranial nerve palsy have been seen in any patient in the study to date.
- The patient that responded to treatment with the combination of birinapant and pembrolizumab had received four prior anti-cancer drug regimens to treat microsatellite stable (MSS) colorectal cancer, a cancer type in which responses to treatment with Keytruda® alone are very rare. This patient has had a confirmed partial response (by RECIST 1.1) to treatment with birinapant and Keytruda®, maintained this response at the last assessment in this interim analysis, and remains on treatment 45 weeks after starting therapy. Three additional patients in the study, with appendiceal cancer, esophageal cancer and sarcoma respectively, have had periods of stable disease lasting for at least 18 weeks following the start of treatment.
- The fourth and final group of patients, which will receive birinapant at 22mg/m2 in combination with Keytruda®, is currently ongoing. The recommended phase II dose will be determined once safety data are available for all patients in the four planned dose groups.
- • On June 4, 2018, the design of the ongoing phase I/II study of birinapant in combination with pembrolizumab in advanced cancer patients has been presented during the 2018 American Society for Clinical Oncology (ASCO) Annual Meeting. The poster presentation has been given by the study’s lead investigator, Prof. Russell J. Schilder, Director of the Medical Gynecologic Oncology Program at Thomas Jefferson University Hospital in Philadelphia, USA (Abstract)
- • On August 18, 2017, Medivir announced that the first patient has been enrolled in its phase I/II study of birinapant in combination with the pembrolizumab. The objectives of the study are to evaluate the safety, tolerability and preliminary efficacy of this combination in patients with treatment-resistant solid tumours.
- The multicentre, single arm, open label study, which is primarily being run in the US, will be conducted in two parts. In the initial dose escalation (phase I) part of the study, the objective is to identify the recommended phase II dose of birinapant for use in combination with pembrolizumab. This is to be achieved by administering increasing doses of birinapant in combination with the approved dose of pembrolizumab to cohorts of up to 6 patients with refractory solid tumours. Once the recommended phase II dose has been identified, the second part of the study will begin.
- The primary objective of the phase II part is to evaluate the safety and tolerability of birinapant in combination with pembrolizumab in several cohorts. Each cohort will be made up of patients with the same treatment refractory tumour type. An important secondary objective in the phase II part is the preliminary evaluation of the efficacy of the combination in each of the cohorts.
Is
general: Yes
