Abstract 275P
Background
In TNBC, despite high initial response to chemotherapy (CT), many pts relapse, and options for treating recurrence are limited. Combining immunotherapy and CT may synergise to enhance therapeutic efficacy. Here we evaluate LAG525, an anti-LAG-3 antibody (ab), with PDR001, an anti-PD-1 ab, and/or carbo in pts with adv TNBC.
Methods
In this phase 2, open-label, 3-arm study, pts with adv TNBC regardless of PDL1 status progressing after adjuvant or 1 prior line of systemic therapy for metastatic disease, but had not received an immune checkpoint inhibitor, were randomised 1:1:1 to LAG525 + PDR001, LAG525 + PDR001 + carbo, or LAG525 + carbo. Stratification factors were presence of liver metastasis and line of therapy. Doses for each drug were LAG525 400 mg, PDR001 300 mg, and/or carbo AUC6, IV Q3W. Primary endpoint was overall response rate (ORR) per RECIST v1.1 and was analysed when all pts had ≥24 weeks follow-up or discontinued tumour assessments for any reason. Proof of preliminary efficacy (PPE) required both a posterior mean ORR ≥35% and a posterior probability of (ORR ≥25%) ≥90%. Further efficacy outcomes and safety were secondary endpoints; biomarker analyses were an exploratory endpoint.
Results
Between 05 JUL 2018 and 09 SEP 2019, 88 pts were enrolled; all had measurable disease. The LAG525 + PDR001 arm was discontinued early due to a high rate of progressive disease. As of the data cut-off on 27 FEB 2020, median follow-up was 12.5 mo. ORR and duration of response (DOR) are summarised in the table. The primary objective was not met: no arms met PPE criteria, although there was a 32.4% observed ORR in the triplet arm. There was 1 treatment-related death in the LAG525 + carbo arm. Table: 275P
| LAG525 + PDR001 n=20* | LAG525 + PDR001 + carbo n=34 | LAG525 + carbo n=34 | |
| ORR, n (%; 95% CI) | 1 (5.0; 0.1 – 24.9) | 11 (32.4; 17.4 – 50.5) | 6 (17.6; 6.8 – 34.5) |
| Posterior mean ORR, % | 7.1 | 32.5 | 18.4 |
| Posterior probability p (ORR ≥25%) | 0.9 | 82.9 | 15.3 |
| DOR, mo (range; no. of events) | 4.9 (NE – NE; 1) | 13.6 (2.8 – NE; 5) | 12.6 (2.4 – NE; 3) |
| Any AE, n (%) | 18 (95) | 34 (100) | 34 (100) |
| Gr ≥3 AE, n (%) | 7 (37) | 30 (88) | 22 (65) |
| Most common Gr ≥3 AEs | - Platelet count decreased, decreased appetite, pleural effusion (n=1 each, 5%) | - Anaemia (n=9, 27%) - Thrombocytopenia, neutrophil count decreased (n=8 each, 24%) | - Anaemia (n=7, 21%)- Thrombocytopenia, neutropenia (n=4 each, 12%) |
*One pt did not receive ≥1 dose of study drug and is not included in safety analysis.
Conclusions
As no arms met the PPE criteria, no further investigation is planned. Anaemia was the most common grade ≥3 AE. Exploratory biomarker analyses are ongoing.
Clinical trial identification
NCT03499899.
Editorial acknowledgement
We thank Casandra M Monzon, PhD, of Healthcare Consultancy Group, LLC, for her medical editorial assistance with this abstract, which was funded by Novartis Pharmaceuticals Corporation.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
L.A. Carey: Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: G1 Therapeutics; Financial Interests, Institutional, Funding: Genetech/Roche; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Institutional, Funding: Innocrin; Financial Interests, Institutional, Funding: Seattle Genetics; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Immunomedics. J. Pierga: Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Research Grant: Servier; Financial Interests, Institutional, Research Grant: Menarini; Financial Interests, Personal, Advisory Role, Consulting: Pfizer; Financial Interests, Personal, Advisory Role, Consulting: MSD; Financial Interests, Personal, Advisory Role, Consulting: Roche; Financial Interests, Personal, Advisory Role, Consulting: Lilly; Financial Interests, Personal, Advisory Role, Consulting: AstraZeneca; Financial Interests, Personal, Advisory Role, Consulting: Daiichi Sankyo; Financial Interests, Personal, Advisory Role, Consulting: Pierre Fabre Oncology; Financial Interests, Personal, Advisory Role, Consulting: Seagen; Financial Interests, Personal, Advisory Role, Consulting: Novartis; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo; Financial Interests, Personal, Other, Honoraria: Pierre Fabre Oncology; Financial Interests, Personal, Other, Honoraria: Seagen; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: ExactSciences; Financial Interests, Personal, Other, Travel Support: Roche; Financial Interests, Personal, Other, Travel Support: Mundipharma; Financial Interests, Personal, Other, Travel Support: Novartis; Financial Interests, Personal, Other, Travel Support: Eisai; Financial Interests, Personal, Other, Travel Support: AstraZeneca; Financial Interests, Institutional, Advisory Board: Sanofi. S. Kümmel: Financial Interests, Personal, Advisory Role, Consulting: Lilly; Financial Interests, Personal, Advisory Role, Consulting: MSD; Financial Interests, Personal, Advisory Role, Consulting: Somatex; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Roche Pharma; Financial Interests, Personal, Other, Honoraria: Genomic Health; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: pfm medical; Financial Interests, Personal, Other, Honoraria: Celgene; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo; Financial Interests, Personal, Other, Honoraria: Somatex; Financial Interests, Personal, Other, Honoraria: Sonoscape; Financial Interests, Personal, Other, Travel Support: Roche Pharma; Financial Interests, Personal, Other, Travel Support: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Roche Pharma; Financial Interests, Personal, Advisory Board: Genomic Health; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: pfm medical; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Somatex; Financial Interests, Personal, Leadership Role, Society Committee: WSG; Financial Interests, Personal, Leadership Role, Society Committee: AGO. G. Jerusalem: Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Other, Consulting: Roche; Financial Interests, Personal, Other, Consulting: Novartis; Financial Interests, Personal, Other, Consulting: Lilly; Financial Interests, Personal, Other, Consulting: Pfizer; Financial Interests, Personal, Other, Consulting: Amgen; Financial Interests, Personal, Other, Consulting: Bristol Myers Squibb; Financial Interests, Personal, Other, Consulting: AstraZeneca; Financial Interests, Personal, Other, Consulting: Daiichi Sankyo; Financial Interests, Personal, Other, Consulting: AbbVie; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Travel Support: Novartis; Financial Interests, Personal, Other, Travel Support: Roche; Financial Interests, Personal, Other, Travel Support: Pfizer; Financial Interests, Personal, Other, Travel Support: Lilly; Financial Interests, Personal, Other, Travel Support: Amgen; Financial Interests, Personal, Other, Travel Support: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel Support: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Other, Receipt of equipment, materials, drugs, medical writing, gifts or other services: Roche; Financial Interests, Personal, Other, Receipt of equipment, materials, drugs, medical writing, gifts or other services: Novartis; Financial Interests, Personal, Other, Receipt of equipment, materials, drugs, medical writing, gifts or other services: Lilly; Financial Interests, Personal, Other, Receipt of equipment, materials, drugs, medical writing, gifts or other services: Pfizer; Financial Interests, Personal, Other, Receipt of equipment, materials, drugs, medical writing, gifts or other services: Amgen; Financial Interests, Personal, Other, Receipt of equipment, materials, drugs, medical writing, gifts or other services: Bristol Myers Squibb; Financial Interests, Personal, Other, Receipt of equipment, materials, drugs, medical writing, gifts or other services: AstraZeneca; Financial Interests, Personal, Other, Receipt of equipment, materials, drugs, medical writing, gifts or other services: MedImmune; Financial Interests, Personal, Other, Receipt of equipment, materials, drugs, medical writing, gifts or other services: MerckKGaA. M. De Laurentiis: Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Eli Lilly; Financial Interests, Institutional, Funding: Pierre Fabre; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: MSD. M. Miller, M. Kaper, F. Su: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. Z. Li: Financial Interests, Personal, Full or part-time Employment: Novartis. S. Loi: Financial Interests, Institutional, Advisory Role: Aduro Biotech; Financial Interests, Institutional, Advisory Role: Novartis; Financial Interests, Institutional, Advisory Role: G1 Therapeutics; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Bristol Myers Squibb; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Roche-Genetech; Financial Interests, Institutional, Funding: Puma Biotechnology; Financial Interests, Institutional, Funding: Eli Lilly.