Abstract 637P
Background
The next-generation tyrosine kinase inhibitors (TKIs) taletrectinib and repotrectinib have demonstrated promising outcomes in clinical trials of patients with advanced/metastatic ROS1+ NSCLC. In the absence of head-to-head trials, we compared taletrectinib and repotrectinib in patients with ROS1+ NSCLC using a MAIC.
Methods
Patients receiving taletrectinib in TRUST I (NCT04395677) and TRUST-II (NCT04919811); data cut-off: March 2024; were pooled and matched to patients receiving repotrectinib in TRIDENT 1 (NCT03093116) on age, gender, ECOG status, disease stage, smoking history, histological classification, baseline CNS disease, and number of previous systemic therapies. Patients were stratified by prior TKI status (naive/pretreated); objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS) were compared. Adjusted Cox regression models computed hazard ratios (HR) and 95% confidence intervals (CI).
Results
After matching, covariates were balanced across the taletrectinib and repotrectinib TKI-naive and TKI-pretreated cohorts. In TKI-naive patients, the ORR for taletrectinib (n=152; 89%) was numerically higher vs repotrectinib (n=71; 79%). In TKI-pretreated patients, the ORR was numerically higher for taletrectinib (n=104; 56%) vs repotrectinib (n=56; 38%) with largely non-overlapping CIs. For both TKI-naive and pretreated patients, the lower bound of the 95% CI for the ORR of taletrectinib exceeded the ORR of repotrectinib (Table). The HRs for DOR and PFS numerically favored taletrectinib but were not statistically significant.
Conclusions
Taletrectinib may induce more frequent tumor responses than repotrectinib in both TKI-naive and TKI-pretreated ROS1+ NSCLC patients. Further analyses with more mature DOR and PFS data are needed to confirm our findings Table: 637P
MAIC: Outcomes comparison in TKI-naive and TKI-pretreated cohorts
| Outcomes | TKI naive | TKI pretreated | ||
| Taletrectinib after matching (N=152) | Repotrectinib (N=71) | Taletrectinib after matching (N=104) | Repotrectinib (N=56) | |
| ORR, % 95% CI | 88.8% 82.7%–93.3% | 78.9% 67.6%–87.7% | 55.8% 45.7%–65.5% | 37.5% 24.9%–51.5% |
| DOR, hazard ratio 95% CI | 0.76 0.404–1.438 | 0.86 0.419–1.776 | ||
| PFS, hazard ratio 95% CI | 0.93 0.656–1.311 | 0.97 0.578–1.612 | ||
DOR, duration of response; MAIC, matching adjusted indirect comparison; ORR, objective response rate; PFS, progression-free survival; TKI, tyrosine kinase inhibitor.
.Clinical trial identification
NCT04395677, NCT04919811.
Editorial acknowledgement
Writing support was provided by Lorena Tonarelli, MSc, of Peloton Advantage, LLC, an OPEN Health company.
Legal entity responsible for the study
AnHeart Therapeutics, a wholly owned subsidiary of Nuvation Bio Inc.
Funding
AnHeart Therapeutics, a wholly owned subsidiary of Nuvation Bio Inc.
Disclosure
M. Nagasaka: Financial Interests, Personal, Advisory Board: AstraZeneca, Caris Life Sciences, Daiichi Sankyo, Novartis, EMD Serono, Janssen, Lilly, Pfizer, Genentech, Mirati, Regeneron, Silverback; Financial Interests, Personal, Invited Speaker: Takeda, Blueprint; Financial Interests, Personal, Other, Travel: AnHeart. G. Liu: Non-Financial Interests, Personal, Other, Honorarium: Takeda, Amgen, AstraZeneca, Roche, Novartis, Merck, Pfizer, Jazz Pharmaceuticals; Financial Interests, Institutional, Funding, Research Grants: Takeda, AstraZeneca, Amgen, Boehringer Ingelheim. N. Pennell: Financial Interests, Personal, Advisory Role: Merck, BMS, Pfizer, Genentech, Sanofi Genzyme, Novartis, Bayer, Summit Therapeutics, AnHeart, Takeda, J&J, Lilly/Regeneron, Iovance. Y. Ohe: Financial Interests, Personal, Advisory Role: AstraZeneca, Chugai, ONO, BMS, Celltrion, Amgen, Nippon Kayaku, Boehringer Ingelheim, AnHeart Therapeutics Inc., PharmaMar; Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Eli Lilly, ONO, BMS, Boehringer Ingelheim, Bayer, Pfizer, MSD, Taiho, Nippon Kayaku, Kyowa Hakko Kirin, Eisai, Daiichi Sankyo; Financial Interests, Personal, Other, Research Expenses: AstraZeneca, Chugai, Lilly, ONO, BMS, Pfizer, Taiho, Novartis, Takeda, Daiichi Sankyo, Janssen. M. Pérol: Financial Interests, Personal, Advisory Board, Advisory board: Roche, AstraZeneca, MSD, BMS, Lilly, Novartis, Takeda, Gritstone, Sanofi, Pfizer, Amgen, Janssen, GSK, Esai, 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, Advisory Board, Expert Testimony: AstraZeneca; Financial Interests, Personal, Steering Committee Member, Steering Committee member: LILLY; Financial Interests, Institutional, Local PI, 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, Trial Chair, Trial Chair: Anheart Therapeutics; Financial Interests, Personal, Steering Committee Member, IDMC Chair: Pharmamar, Sophiagenetics; Financial Interests, Personal, Steering Committee Member, Steering Committee Member: ROCHE; Financial Interests, Personal, Other, DMSB: ROCHE. S. Li: Financial Interests, Personal, Full or part-time Employment: Nuvation Bio, Inc. 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, Inc., Janssen/J&J, Novocure, ORIC, Regeneron, Pfizer, Sanofi, Teligene, Boehringer Ingelheim. C. Zhou: Financial Interests, Personal, Other, Honoraria: Amoy Diagnostics, Boehringer Ingelheim, CStone 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, CStone Pharmaceuticals, Hengrui Pharmaceutical, Innovent Biologics, Lilly China, Luye Pharma, MSD, QiLu Pharmaceutical, Roche, Sanofi, TopAlliance Biosciences Inc.