1393TiP - A phase II/III study to evaluate the optimal dose, safety, and efficacy of livmoniplimab (Livmo) in combination with budigalimab (Budi) plus chemotherapy (CT) vs pembrolizumab (Pembro) plus CT in untreated metastatic non-small cell lung cancer (mNSCLC)

Background

The standard 1L treatment (Tx) for patients (pts) with untreated mNSCLC is pembro + CT. However, there is an unmet need for novel Tx options, especially for pts with primary/secondary resistance to 1L SOC or poor response due to liver metastases (met). Livmo (ABBV-151), a first-in-class monoclonal antibody (mAb), targets the GARP-TGF-β1 complex, promoting immunoreactivity. The mAb budi (ABBV-181), binds to cell surface-expressed PD-1, resulting in checkpoint blockade. Livmo + budi has shown promising clinical activity in solid tumors. We describe a study to evaluate the combination of livmo and budi + CT vs pembro + CT in pts with mNSCLC.

Trial design

This multicenter phase 2/3 study (NCT06236438) will evaluate the optimal dose, safety, and efficacy of livmo and budi + CT vs pembro + CT in untreated mNSCLC. Eligible pts (≥18 years) have histologically/cytologically confirmed non-squamous mNSCLC with no known EGFR/ALK mutation or other targetable genomic aberration, ≥1 measurable lesion per RECIST v1.1, no prior Tx for mNSCLC, ECOG PS 0-2, and documented PD-L1 status. Stage 1 (phase 2, open label, ∼160 pts) comprises 4 parallel pt cohorts (randomized 1:1:1:1): livmo (dose A/B) and budi + CT, budi + CT, or pembro + CT. An initial safety lead-in for each cohort following a 6 + 3 design will be implemented. After the safety lead-in is completed and it is deemed safe to expand, additional pts will be enrolled into each cohort. The optimal livmo dose will be identified after all pts have enrolled and have ≥4 months follow-up. Stage 2 (phase 3, double-blind, ∼680 pts) includes 2 Tx arms (randomized 1:1): livmo (optimized dose) and budi + CT or placebo and pembro + CT. Pts receive Tx until a max of 35 cycles (1 cycle = 3 weeks) or meeting discontinuation criteria. Objectives and endpoints are in the table. Enrollment is ongoing in ∼200 sites globally. Table: 1393TiP

RP3D, recommended phase III dose; BOR, best overall response; C/PR, complete/partial response; Inv, investigator; PFS, progression-free survival; DOR, duration of response; OS, overall survival; PRO, patient reported outcome; BICR, blinded central review

Clinical trial identification

NCT06236438.

Editorial acknowledgement

Medical writing support was provided by Delyth Eickermann, PhD, from Aptitude Health, The Hague, the Netherlands, and funded by AbbVie.

Legal entity responsible for the study

AbbVie.

Funding

AbbVie.

Disclosure

N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi, Gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Other, Family member is an employee: AstraZeneca. A. Zer: Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, Takeda, Pfizer, Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca, Steba, Oncohost; Financial Interests, Personal, Other, Safety Review Committee Member: Beyond Air; Financial Interests, Personal, Stocks/Shares: Nixio; Financial Interests, Institutional, Research Grant: BMS. L.E. Raez: Financial Interests, Personal and Institutional, Research Grant: AbbVie, Amgen, AstraZeneca, BMS, Daiichi Sankyo, Merck, Lilly Oncology, Loxo Pharmaceuticals, ONC4, Velos, Natera, Guardant, Bayer, TSCAN, TG therapeutics; Financial Interests, Personal, Speaker, Consultant, Advisor: Merck, BMS, Bayer, Daiichi Sankyo, Lilly Oncology, Loxo Pharmaceuticals. H. Horinouchi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly, BMS/Ono, Merck Sharp & Dohme, Roche/Chugai, Novartis, Pfizer, Boehringer Ingelheim, Kyowa-Kirin, Nihon Kayaku, AbbVie; Financial Interests, Personal, Advisory Board: AstraZeneca, Eli Lilly, BMS/Ono, Merck Sharp & Dohme, Roche/Chugai, Amgen, Nihon Kayaku; Financial Interests, Personal, Steering Committee Member: Roche/Chugai; Financial Interests, Institutional, Research Grant: Roche/Chugai, Merck Sharp & Dohme, Daiichi Sankyo, Ono Pharmaceutical, AstraZeneca; Financial Interests, Institutional, Local PI: AbbVie. J. Zugazagoitia: Financial Interests, Personal, Invited Speaker: Takeda, BMS, AstraZeneca, NanoString, Guardant Health; Financial Interests, Personal, Advisory Board: Roche, Sanofi, BMS, Pfizer, Novartis, Janssen; Financial Interests, Personal and Institutional, Funding, Research Grant: AstraZeneca, Roche, BMS. X. Chen, S. Jha, C. Ferlini, D. Ngo: Financial Interests, Personal, Full or part-time Employment: AbbVie; Financial Interests, Personal, Stocks/Shares: AbbVie.