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Josef Straub
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MA09 - EGFR & MET (ID 128)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:Jordi Remon, Juergen Wolf
- Coordinates: 9/08/2019, 15:15 - 16:45, Melbourne (1991)
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MA09.09 - Long-Term Outcomes to Tepotinib Plus Gefitinib in Patients with <i>EGFR</i>-Mutant NSCLC and MET Dysregulation: 18‑Month Follow-Up (Now Available) (ID 1783)
15:15 - 16:45 | Author(s): Josef Straub
- Abstract
- Presentation
Background
In EGFR-mutant NSCLC, MET amplification may cause resistance to EGFR tyrosine kinase inhibitors (TKIs). In a Phase Ib/II study in EGFR TKI-resistant patients with EGFR-mutant MET+ NSCLC, progression-free survival (PFS) and objective response rate (ORR) after ≥6 months of follow-up were improved with tepotinib (a highly selective MET TKI) plus gefitinib, compared with chemotherapy, particularly in patients with MET amplification. Here we present data at ≥18 months of follow-up.
Method
Asian patients with advanced, EGFR+, T790M-, MET+ NSCLC with resistance to prior EGFR TKIs were randomized to receive oral tepotinib 500 mg/day+gefitinib 250 mg/day or ≤6 cycles of cisplatin/carboplatin+pemetrexed chemotherapy±pemetrexed maintenance until confirmed progression, unacceptable toxicity, or withdrawal. Primary endpoint was investigator-assessed PFS. Secondary endpoints included ORR, overall survival (OS) and safety. Subgroup analyses were preplanned in MET IHC3+ and MET amplification populations (NCT01982955).
Result
Low recruitment halted full enrolment with 55 of 156 planned patients enrolled.
As of 12-Dec-2018, median (range) duration of treatment with tepotinib+gefitinib was 21.4 (4.6, 110.9) weeks, with 3 patients still receiving treatment; and with pemetrexed was 18.0 (3.0, 60.4) weeks. 15 patients (62.5%) received ≥4 cisplatin/carboplatin cycles.
Better outcomes were reported with tepotinib+gefitinib vs chemotherapy (Table), particularly in patients with MET IHC3+ (PFS: HR 0.35 [90% CI 0.17–0.74], OS: 0.32 [0.14–0.75]) or MET amplification (PFS: HR 0.13 [90% CI 0.04–0.43], OS: 0.08 [0.01–0.51]).
Drug-related grade ≥3 adverse events (AEs) occurred in 17 (54.8%) patients receiving tepotinib+gefitinib and 12 (52.2%) patients receiving chemotherapy. Any-cause AEs leading to discontinuation occurred in 3 (9.7%) patients receiving tepotinib+gefitinib and 1 (4.3%) receiving chemotherapy. Dose reductions due to AEs were reported in 5 (16.1%) vs 4 (17.4%) patients.
Conclusion
Tepotinib+gefitinib has durable antitumor activity in patients with EGFR-mutant NSCLC with MET IHC3+ or MET amplification, and was generally well tolerated. MET amplification will be further explored as a biomarker for tepotinib.
Table: Summary of efficacy data
Population
Tepotinib + gefitinib
Chemotherapy
HR/OR
(90% CI)Overall MET+*
Patients, n
31
24
mPFS, months (90% CI)
4.9 (3.9, 6.9)
4.4 (4.2, 6.8)
0.67 (0.35, 1.28)
mOS, months (90% CI)
17.3 (12.1, 37.3)
18.7 (15.9, 20.7)
0.67 (0.33, 1.37)
ORR, n (%) [90% CI]
14 (45.2) [29.7, 61.3]
8 (33.3) [17.8, 52.1]
1.99 (0.56, 6.87)
MET IHC3+
Patients, n
19
15
mPFS, months (90% CI)
8.3 (4.1, 21.2)
4.4 (4.1, 6.8)
0.35 (0.17, 0.74)
mOS, months (90% CI)
37.3 (24.2, 37.3)
17.9 (12.0, 20.7)
0.32 (0.14, 0.78)
ORR, n (%) [90% CI]
13 (68.4) [47.0, 85.3]
5 (33.3) [14.2, 57.7]
4.33 (1.03, 18.33)
MET amplification†
Patients, n
12
7
mPFS, months (90% CI)
21.2 (8.3, NE)
4.2 (1.4, 7.0)
0.13 (0.04, 0.43)
mOS, months (90% CI)
37.3 (NE, NE)
13.1 (3.3, NE)
0.08 (0.01, 0.51)
ORR, n (%) [90% CI]
8 (66.7) [39.1, 87.7]
3 (42.9) [12.9, 77.5]
2.67 (0.37, 19.56)
CEP-7, centromere protein 7; CI, confidence interval; EGFR, epidermal growth factor receptor; GCN, gene copy number; HR, hazard ratio; IHC, immunohistochemistry; IRC, independent review committee; ITT, intention to treat; MET, mesenchymal-epithelial transition factor; NE, not estimable; OR, odds ratio; ORR, objective response rate; OS, overall survival; PFS, progression-free survival
All efficacy outcomes are investigator-assessed by RECIST v1.1.
*IHC2+/IHC3+/gene amplification.
†MET amplification is defined as GCN ≥5 and/or MET/CEP-7 ratio ≥2. 17 of 19 patients with MET amplification have MET overexpression (IHC3+).
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