Abstract 1211P
Background
Mobocertinib, a novel EGFR tyrosine kinase inhibitor (TKI), demonstrated clinically meaningful benefit in platinum-pretreated patients with EGFR exon 20 insertion mutant (EGFRex20ins+) non-small cell lung cancer (NSCLC) in an open-label, multicenter clinical trial. This study describes an indirect comparison of clinical outcomes for platinum-pretreated patients with EGFRex20ins+ NSCLC treated with mobocertinib in a clinical trial vs. standard of care (SoC) from real-world data (RWD).
Methods
Clinical outcomes were compared for platinum-pretreated patients with EGFRex20ins+ NSCLC treated with mobocertinib 160 mg QD in a phase I/II trial (NCT02716116; cutoff 1 Nov 2020) vs. SoC in the post-platinum second or later line (≥2L) setting from the Flatiron electronic health record database (RWD; cutoff 29 Feb 2020). The analysis was conducted in an unadjusted data set and using propensity score modeling with inverse probability of treatment weighting (IPTW) to adjust for group differences in key baseline characteristics. Confirmed overall response rate (cORR), progression-free survival (PFS), and overall survival (OS) were compared between groups.
Results
This study included 164 platinum-pretreated patients (n=114 mobocertinib/n=50 RWD; mean age 60/64 years; female, 66%/68%; smoking history 29%/42%; with baseline brain metastasis, 35%/34%). In the RWD, ≥2L SoC treatment consisted of 20% EGFR TKI, 40% immunotherapy alone, and 40% chemotherapy ± immunotherapy or monoclonal antibody. Baseline characteristics were balanced after weighting. In the weighted cohort, cORR for mobocertinib vs. RWD was 35 % vs. 12%, median PFS was 7.3 vs. 3.3 mo, and median OS was 24.0 vs. 12.4 mo, respectively (Table). Table: 1211P
| Mobocertinib (n=114)a | RWD Post-platinum ≥2L b | ||
| Unweighted (n=50) | Weighted (n=109) | ||
| cORR % (95% CI) | 35 (26, 45) | 14 (6, 27) | 12 (6, 18) |
| Rate difference % (95% CI) | 21 (8, 34) | 23 (12, 34) | |
| Odds ratio (95% CI)c P-value | 3.32 (1.68, 6.58) 0.0006 | 3.75 (2.05, 6.89) <0.001 | |
| Median PFS, mo (95% CI) | 7.3 (5.6, 8.8) | 3.3 (2.3, 5.9) | 3.3 (2.2, 7.3) |
| HR (95% CI)d P-value | 0.57 (0.36, 0.89) 0.0149 | 0.57 (0.36, 0.90) 0.0153 | |
| Median OS, mo (95% CI) | 24.0 (14.6, 28.8) | 11.5 (7.9, 16.6) | 12.4 (7.1, 16.6) |
| HR (95% CI)d P-value | 0.54 (0.34, 0.84) 0.0068 | 0.53 (0.33, 0.83) 0.0056 |
acORR and PFS: per investigator using RECIST 1.1 bcORR: confirmed real-world response by radiologic imaging cLogistic model dCox model CI, confidence interval; HR, hazard ratio
Conclusions
Mobocertinib was associated with significant improvements in cORR, PFS, and OS compared to SoC used in the in platinum-pretreated patients with EGFRex20ins+ NSCLC.
Clinical trial identification
Editorial acknowledgement
Medical writing support was provided by Jane Kondejewski, PhD of Snell Medical Communication Inc., Montreal, QC, Canada.
Legal entity responsible for the study
Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Funding
Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Disclosure
S.I. Ou: Financial Interests, Personal, Other, Personal fees: Pfizer Inc.; Financial Interests, Personal, Other, Personal fees: AstraZeneca; Financial Interests, Personal, Other, Personal fees: Takeda Pharmaceutical Company Limited/ARIAD; Financial Interests, Personal, Other, Personal fees: Roche/Genentech; Financial Interests, Personal, Other, Personal fees: Daiichi Sankyo; Financial Interests, Personal, Other, Personal fees: Janssen/Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Turning Point Therapeutics; Financial Interests, Personal, Stocks/Shares: Elevation Oncology. H.M. Lin: Other, Personal and Institutional, Full or part-time Employment: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited; Financial Interests, Personal, Stocks/Shares: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. J. Hong: Other, Personal and Institutional, Full or part-time Employment: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited; Financial Interests, Personal, Stocks/Shares: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Y. Yin: Other, Personal and Institutional, Full or part-time Employment: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited; Financial Interests, Personal, Stocks/Shares: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. S. Jin: Other, Personal and Institutional, Full or part-time Employment: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited; Financial Interests, Personal, Stocks/Shares: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. J. Lin: Other, Personal and Institutional, Full or part-time Employment: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited; Financial Interests, Personal, Stocks/Shares: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. M. Mehta: Other, Personal and Institutional, Full or part-time Employment: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited; Financial Interests, Personal, Stocks/Shares: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. J.W. Neal: Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Institutional, Advisory Role: Genentech/Roche; Financial Interests, Institutional, Advisory Role: Exelixis; Financial Interests, Institutional, Advisory Role: Jounce Therapeutics; Financial Interests, Institutional, Advisory Role: Takeda Pharmaceutical Company Limited; Financial Interests, Institutional, Advisory Role: Eli Lilly and Company; Financial Interests, Institutional, Advisory Role: Calithera Biosciences; Financial Interests, Institutional, Advisory Role: Amgen; Financial Interests, Institutional, Advisory Role: Iovance Biotherapeutics; Financial Interests, Institutional, Advisory Role: Blueprint Pharmaceuticals; Financial Interests, Institutional, Advisory Role: Regeneron Pharmaceuticals; Financial Interests, Institutional, Advisory Role: Natera; Financial Interests, Institutional, Other, Received honoraria: CME Matters; Financial Interests, Institutional, Other, Received honoraria: Clinical Care Options CME; Financial Interests, Institutional, Other, Received honoraria: Research to Practice CME; Financial Interests, Institutional, Other, Received honoraria: Medscape CME; Financial Interests, Institutional, Other, Received honoraria: Biomedical Learning Institute CME; Financial Interests, Institutional, Other, Received honoraria: MLI PeerView CME; Financial Interests, Institutional, Other, Received honoraria: priME Oncology CME; Financial Interests, Institutional, Other, Received honoraria: Projects in Knowledge CME; Financial Interests, Institutional, Other, Received honoraria: Rockpointe CME; Financial Interests, Institutional, Other, Received honoraria: MJH Life Sciences CME; Financial Interests, Institutional, Royalties: UpToDate Financial Interests, Institutional, Funding: Genentech/Roche; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Boehringer Ingelheim; Financial Interests, Institutional, Funding: Exelixis; Financial Interests, Institutional, Funding: Nektar Therapeutics; Financial Interests, Institutional, Funding: Takeda Pharmaceutical Company Limited; Financial Interests, Institutional, Funding: Adaptimmune; Financial Interests, Institutional, Funding: GlaxoSmithKline; Financial Interests, Institutional, Funding: Janssen/Johnson & Johnson; Financial Interests, Institutional, Funding: AbbVie. All other authors have declared no conflicts of interest.