LBA2 - Taletrectinib vs crizotinib in ROS1-positive (ROS1+) non-small cell lung cancer (NSCLC): A matching-adjusted indirect comparison (MAIC)

Background

We compared taletrectinib, a highly potent, next-generation, selective, central nervous system-active, ROS1-positive (ROS1+) tyrosine kinase inhibitor (TKI), with crizotinib, a first-generation

TKI. In the absence of head-to-head trials, we used a matching-adjusted indirect comparison (MAIC) to focus on TKI-naive patients with ROS1+ non-small cell lung cancer (NSCLC).

Methods

Pooled patient data for taletrectinib (N=160 for TKI-naive patients) were obtained from the TRUST-I (NCT04395677) and TRUSTII (NCT04919811) studies (data cutoff: June 2024). These patients were matched to patients receiving crizotinib (N=53) in the PROFILE 1001 study on gender, ECOG status, smoking history, histologic classification, and number of previous systemic therapies. Objective response rate (ORR), progression-free survival (PFS), overall survival, and grade 3 treatment-related adverse event (TRAE) rates were evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using adjusted Cox regression models.

Results

Prior to matching, key baseline characteristics differed between the taletrectinib and crizotinib cohorts but were well-balanced after match-adjustment, creating comparable cohorts for the indirect comparison. The ORR for taletrectinib was higher (90.1% [95% CI: 78.5%, 96.7%]) vs crizotinib (71.7% [95% CI: 57.7%, 83.2%]). The HRs for PFS (0.48 [95% CI: 0.27, 0.88]) and OS (0.34 [95% CI: 0.15, 0.77]) indicated a statistically significant 52% reduction in the risk of disease progression and a 66% reduction in the risk of death with taletrectinib vs crizotinib. The incidence of grade 3 TRAEs was comparable between taletrectinib and crizotinib (45% [95% CI: 31.2%, 59.8%] vs 36% [95% CI: 23.1%, 50.2%], respectively).

Conclusions

In this cross-trial MAIC analysis, taletrectinib showed significantly improved outcomes compared with crizotinib in TKI-naive patients with ROS1+ NSCLC, including higher ORR, a significant reduction in the risk of disease progression and mortality, and with comparable grade 3 TRAEs.

Clinical trial identification

NCT04395677. NCT04919811.

Editorial acknowledgement

Writing support was provided by Tulika Bhushan Bahukhandi, RPh, MS, of Peloton Advantage, LLC, an OPEN Health company, and was funded by Nuvation Bio.

Legal entity responsible for the study

Nuvation Bio Inc.

Funding

Nuvation Bio Inc.

Disclosure

M. Nagasaka: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Takeda, Novartis, EMD Serono, Pfizer, Lilly, Regeneron, Genentech; Financial Interests, Personal, Other, Consultancy (Virtual Tumor Board): Caris Life Sciences; Financial Interests, Personal, Invited Speaker: Blueprint Medicines, Janssen, Mirati, Takeda; Financial Interests, Personal, Other, Travel Support: Nuvation Bio Inc. G. Liu: Non-Financial Interests, Personal, Other, Honoraria: Takeda, Amgen, AstraZeneca, Roche, Novartis, Merck, Pfizer, Jazz Pharmaceuticals; Financial Interests, Institutional, Funding: Takeda, AstraZeneca, Amgen, Boehringer Ingelheim. N. Pennell: Financial Interests, Personal, Advisory Role: Merck, BMS, Pfizer, Genentech, Sanofi Genzyme, Novartis, Bayer, Summit Therapeutics, AnHeart Therapeutics, Takeda, J&J, Lilly/Regeneron, Iovance. M. Pérol: Financial Interests, Personal, Advisory Board, Advisory board: Roche, AstraZeneca, MSD, BMS, Lilly, Novartis, Takeda, Gritstone, Sanofi, Pfizer, Amgen, Janssen, GSK, Eisai, Ipsen, Novocure, AbbVie, Anheart Therapeutics, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, Symposium: Roche, AstraZeneca, MSD, BMS, Boehringer Ingelheim, Takeda, Illumina, Pfizer, Medscape; Financial Interests, Personal, Expert Testimony, Expert Testimony: AstraZeneca; Financial Interests, Personal, Invited Speaker, Steering Committee member: Lilly; Financial Interests, Institutional, Invited Speaker, Local PI: AbbVie, Amgen, Anheart Therapeutics, Apollomics, Arrivent Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Innate Pharma, Roche; Financial Interests, Institutional, Research Grant, Resarch grant: AstraZeneca, Boehringer Ingelheim, Roche, Takeda; Financial Interests, Personal, Invited Speaker, Trial Chair: Anheart Therapeutics; Financial Interests, Personal, Invited Speaker, IDMC Chair: PharmaMar, Sophiagenetics; Financial Interests, Personal, Invited Speaker, Steering Committee Member: Roche; Financial Interests, Personal, Other, DMSB: Roche. M. Chen: Financial Interests, Personal, Full or part-time Employment: Nuvation Bio. L. Bazhenova: Financial Interests, Personal, Advisory Board: Nuvation Bio Inc., Bayer, Daiichi Sankyo, Genentech, Gilead Sciences, Janssen/J&J, Novocure, ORIC, Regeneron, Pfizer, Sanofi, Teligene, Boehringer Ingelheim. C. Zhou: Financial Interests, Personal, Other, Honoraria: Amoy Diagnostics, Boehringer Ingelheim, C-Stone Pharmaceuticals, Hengrui Pharmaceutical, Innovent Biologics, Lilly China, LUYE Pharma, MSD, QiLu Pharmaceutical, Roche, Sanofi, TopAlliance Biosciences Inc.; Financial Interests, Personal, Advisory Role: Amoy Diagnostics, Boehringer Ingelheim, C-Stone Pharmaceuticals, Hengrui Pharmaceutical, Innovent Biologics, Lilly China, Luye Pharma, MSD, QiLu Pharmaceutical, Roche, Sanofi, TopAlliance Biosciences Inc.