Abstract 971TiP
Background
The PACIFIC trial established up to 12 months consolidation therapy with durvalumab as standard of care (SoC) for patients (pts) with unresectable Stage III non-small-cell lung cancer (NSCLC) and no progression after platinum-based cCRT. To improve outcomes further in this population, novel immunotherapy combinations that build on the backbone of PD-L1 inhibition with durvalumab are being explored. Domvanalimab (AB154) is an Fc-silent humanised IgG1 MoAb that blocks interaction of the T cell immunoreceptor with Ig and ITIM domains (TIGIT; upregulated by immune cells) with CD112 and CD155 (expressed by tumour and antigen-presenting cells), reducing inhibition of T cells and natural killer cells and, thereby, promoting antitumour activity. The combination of TIGIT inhibition with PD-(L)1 inhibition has shown encouraging activity in phase 1 and 2 trials in metastatic NSCLC, with enriched benefit observed among pts with PD-L1 positive tumours (Rodriguez-Abreu, et al. 2020; Niu, et al. 2020). PACIFIC-8 (NCT05211895) is assessing the efficacy and safety of durvalumab combined with domvanalimab as consolidation therapy in pts with unresectable Stage III NSCLC and PD-L1 tumour cell (TC) expression.
Trial design
PACIFIC-8 is a phase 3, double-blind, placebo (pbo)-controlled randomised global trial. Eligible pts (≥18 years) must have PD-L1 positive, unresectable Stage III NSCLC (TC expression ≥1% by central lab; VENTANA SP263 IHC assay), WHO performance status 0/1, documented EGFR/ALK wild-type tumour status and not have progressed following definitive platinum-based cCRT (≥2 cycles). Pts (N∼860) will be randomised (1:1) to receive SoC durvalumab (1500 mg IV) combined with either domvanalimab (20 mg/kg IV) or pbo, every 4 weeks for up to 12 months. The primary endpoint is progression-free survival (PFS; RECIST v1.1; BICR) in pts with PD-L1 TC ≥50%. Secondary endpoints include PFS (RECIST v1.1; BICR) in pts with PD-L1 TC ≥1%, overall survival, objective response rate and duration of response (RECIST v1.1; BICR), safety/tolerability, and pt-reported outcomes. Enrolment is ongoing.
Clinical trial identification
NCT05211895, release date: January 27, 2022.
Editorial acknowledgement
Medical writing support for the development of this abstract, under the direction of the authors, was provided by Aaron Korpal, PhD, and Andrew Gannon, MS, MA, of Ashfield MedComms (Manchester, UK), an Ashfield Health company.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
M. Ozguroglu: Non-Financial Interests, Personal and Institutional, Invited Speaker, ESMO IO Geneva: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Regeneron, Bayer; Other, Personal and Institutional, Principal Investigator, Financial and non-financial interest: AstraZeneca, MSD, Roche, Bayer, Gilead, Novartis, Sanofi, Janssen, Regeneron; Other, Personal, Member, Steering committee membership; Financial and non-financial interest: AstraZeneca, Bayer, Regeneron. B. Levy: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Jannsen, Daiichi Sankyo, Takeda, Genentech, Eli Lilly, Novartis, Amgen, Mirati. H. Horinouchi: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Eli Lilly, Ono, BMS, Chugai, Roche, Kyowa-Kirin, Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca, Eli Lilly, Chugai, Roche, Ono, BMS, MSD; Financial Interests, Institutional, Research Grant: MSD, AbbVie, AstraZeneca, BMS, Ono, Merck Biopharma, Daiichi-Sankyo, Janssen, Genomic Health, Chugai, Roche, Novartis. E. Grainger: Financial Interests, Personal and Institutional, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Ownership Interest: AstraZeneca. P. Phuong: Financial Interests, Institutional, Full or part-time Employment: Arcus; Financial Interests, Institutional, Stocks/Shares: Arcus. D.A. Peterson: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M. Newton: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Spira: Financial Interests, Personal, Stocks/Shares: Eli Lilly; Financial Interests, Institutional, Funding: LAM Therapeutics, Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol-Myers Squibb, Loxo, Arch Therapeutics, Gritstone, Plexxikon, Amgen, Daiichi Sankyo, ADCT, Janssen Oncology, Mirati Therapeutics, Rubius, Synthekine, Mersana, Blueprint Medicines; Financial Interests, Personal, Advisory Role: Incyte, Amgen, Novartis, Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Takeda, Janssen Research & Development, Mersana, Gritstone Bio, Daiichi-Sankyo/AstraZeneca, Array BioPharma, AstraZeneca/MedImmune, Merck, Bristol-Myers Squibb, Blueprint Medicines; Financial Interests, Personal, Other, Honoraria: CytomX Therapeutics, AstraZeneca/MedImmune, Merck, Takeda, Amgen, Janssen Oncology, Novartis, Bristol-Myers Squibb, Bayer. All other authors have declared no conflicts of interest.