Clinical Trials

Date: 2017-09-11

Type of information: Presentation of results at a congress

phase: 1

Announcement: presentation of results at the European Society for Medical Oncology (ESMO) 2017 Congress

Company: Tesaro (US - MA)

Product: TSR-042

Action mechanism:

• monoclonal antibody/immune checkpoint inhibitor. TSR-042 is a monoclonal antibody targeting PD-1. It binds with high affinity to PD-1 resulting in inhibition of binding to programmed death receptor ligands 1 and 2 (PD-L1 and PD-L2).
• The antibody was developed as part of the collaboration between Tesaro and AnaptysBio. This collaboration was initiated in March of 2014, and is focused on the development of monospecific antibody drugs targeting PD-1, TIM-3 (TSR-022), and LAG-3 (TSR-033), in addition to a bi-specific antibody drug candidate targeting PD-1/LAG-3.

Disease: advanced solid tumors

Therapeutic area: Cancer - Oncology

Country: Canada, Czechia, France, Italy, Poland, Spain, UK, USA

Trial details:

• This is a multicenter, open-label, first-in-human Phase 1 study evaluating the anti-programmed death receptor 1 (anti-PD-1) antibody TSR-042 in patients with advanced solid tumors who have limited available treatment options. The study will be conducted in 2 parts: dose escalation and cohort expansion. The cohort expansion may include up to 5 tumor types, including endometrial and Non-Small Cell Lung cancer. (NCT02715284)

Latest news:

• • On September 11, 2017, Tesaro provided a summary of TSR-042 data presented at the 2017 European Society of Medical Oncology (ESMO) Annual Meeting in Madrid. In a poster display session, preliminary safety, efficacy, receptor occupancy, and pharmacokinetic data for TSR-042 were presented from a two-part Phase 1 study. No dose limiting toxicities were observed. Adverse events included fatigue, nausea, arthralgia, decreased appetite, and pruritus, which occurred in ?10% of patients. In Part 1 (n=21), two patients with ovarian cancer and small cell lung cancer who were treated with TSR-042 experienced a partial response and five patients with fallopian tube or ovarian cancer had stable disease, two of whom are continuing treatment. Consistent with data reported for other anti-PD-1 antibodies, maximum direct and functional receptor occupancy was observed with both CD3+ binding and IL-2 stimulation assays at all three dose levels evaluated. In Part 2A (n=13), full receptor occupancy, as assessed by the assays used in Part 1, was maintained over 3 and 6 weeks at doses of 500 mg and 1,000 mg, respectively.
• These preliminary findings indicate that TSR-042 is safe and well tolerated, with a safety and efficacy profile expected for an agent targeting the PD-1 pathway, evidence of linear PK, and sustained target engagement at administration intervals up to 6 weeks. The recommended Phase 2 dose was established at 500 mg Q3W for the first four cycles and 1000 mg Q6W thereafter. Serum concentrations of TSR-042 observed 3 weeks after the 500 mg dose were comparable to those observed 6 weeks after the 1000 mg dose. Patients with microsatellite instability high (MSI-H) and microsatellite stable endometrial cancer and non-small cell lung cancer are currently enrolling in the expansion phase of this study, and additional tumor types are planned for evaluation.     • On April 27, 2017, Tesaro announced that following the recent identification of a fixed dose and patient-centric dosing schedule, the ongoing clinical trial of TSR-042 has been expanded to enroll patients with metastatic microsatellite instability high (MSI-H) endometrial cancer who have progressed following one or two prior chemotherapy treatments.
• During the first 12 weeks of treatment, TSR-042 is administered once every three weeks, followed by a single dose administration every six weeks until disease progression.
• The intent of this study is to support a request for accelerated approval and Biologics License Application (BLA) submission to the FDA. The primary endpoints of this trial are overall response rate (ORR) and duration of response, and secondary endpoints include disease control rate, progression free survival (PFS), and overall survival (OS). The addition of cohorts for patients with other tumor types is also planned.

Is general: Yes