Clinical Trials

Date: 2015-11-12

Type of information: Presentation of results at a congress

phase: 1b

Announcement: presentation of results at the San Antonio Breast Cancer Symposium 2015 congress

Company: Roche (Switzerland)

Product: atezolizumab (MPDL3280A)

Action mechanism:

immunotherapy product/monoclonal antibody/immune checkpoint inhibitor. Atezolizumab (MPDL3280A) is an anti-PDL1 monoclonal antibody designed to make cancer cells more vulnerable to the body’s immune system by interfering with a protein called PD-L1. PD-L1 is found on the surface of cells in tumours and is believed to act as a “stop sign,” preventing the immune system from destroying cancer cells. By inhibiting PD-L1, the antibody may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells.

Disease: triple-negative breast cancer (TNBC)

Therapeutic area: Cancer - Oncology

Country:

Trial details:

The study is a multicentre, multi-arm phase Ib study aimed to evaluate atezolizumab in combination with weekly nab-paclitaxel in patients with metastatic TNBC previously treated with systemic cytotoxic therapy. Primary endpoints were safety and tolerability, with secondary endpoints including efficacy using RECIST v1.1 criteria (best overall response, objective response rate, duration of response, progression-free survival), pharmacokinetics, as well as biomarker analyses.
Patients received atezolizumab 800 mg once every 2 weeks (days 1 and 15) with nab-paclitaxel 125 mg/m(2) weekly (days 1, 8 and 15) for 3 weeks in 4-week cycles, until loss of clinical benefit. All patients were women with a median age of 58 years (range 32–75 years).
PD-L1 expression was assessed for both tumour cells (TCs) and immune cells (ICs); people were scored as IC0, 1, 2 or 3 and TC0, 1, 2 or 3 with an immunohistochemistry (IHC) test being developed by Roche Tissue Diagnostics.Expression of PD-L1 in TNBC was mostly restricted to IC

Latest news:

• On November 12, 2015, Roche presented results from a phase Ib study of atezolizumab (MPDL3280A) used in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer (TNBC) at the San Antonio Breast Cancer Symposium 2015 congress. The study showed that the combination shrank tumours (overall response rate, including unconfirmed responses) in 70.8% of people, [n=24; 95% confidence interval, (CI): 48.9, 87.4]. 11 of 17 responses (65%) continued on treatment at time of data cut-off. The highest overall response rate observed [88.9% (CI: 51.7, 99.7)] was in people receiving their initial (1st line) treatment for metastatic disease, with 1 confirmed complete responder. Responses were observed in both PD-L1 positive and PD-L1 negative patients. In addition, some patients with evidence of RECIST based progressive disease developed further response with continued treatment. Adverse events (AEs) were consistent with what has previously been reported for treatment of nab-paclitaxel alone, with 56% of patients (n=32) experiencing Grade 3–4 AEs.
Summary of Best Overall Responses by RECIST v1.1:

• (a)Confirmed ORR defined as at least 2 consecutive assessments of complete or partial response. • (b)Including investigator-assessed unconfirmed responses.
• Efficacy-evaluable patients were dosed by June 1, 2015, and were evaluable for response by RECIST v1.1. • Minimum efficacy follow up was = 3months. • Response rates were higher for patients who received atezolizumab/nab-paclitaxel treatment as 1L therapy compared to 2L+. • Tumour burden and response was monitored in individual patients over the course of treatment. • Three patients developed new lesions while experiencing a partial response in their target lesions; these patients remained on treatment with continued control of their overall tumour burden. • In the 1L group, the median duration of confirmed response was not reached. • In the 2L group, the median duration of confirmed response was 5.4 months. • In the 3L group, the median duration of confirmed response was 3.7 months.
Objective Response Rate by PD-L1 Expression Level(a)

• (a) Including investigator assessed unconfirmed responses • Responses were observed in both ICO and IC1/2/3 patients
Safety
Treatment-related Adverse Events(a)

AE, n (%)	Grade 3-4 = 5% N = 32	All Grade^b N = 32
All	56%	100%
Neutropenia/decreased neutrophil count	41%	53%
Thrombocytopenia/decreased platelet count	9%	16%
Anaemia	6%	19%

• (a)With corresponding incidence of all-grade AEs. • (b)Includes events attributed to either nab-paclitaxel or atezolizumab. • Median safety follow up was 5.2 months (range 0.6–12.6). • 100% of patients experienced an AE of any cause. • No treatment-related deaths were observed. • 5 patients discontinued nab-paclitaxel due to an AE: 1 each for fatigue and asthenia (Grade 2), 3 for peripheral neuropathy (1 each Grade 1, 2, and 3).
Based on these results and the observed activity of single-agent atezolizumab in these patients, Roche is evaluating the combination of atezolizumab and nab-paclitaxel in a phase III study (IMpassion130; NCT02425891) of patients with previously untreated metastatic TNBC.