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Chee Khoon Lee
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OA04 - New Data from Rare EGFR Alterations (ID 223)
- Event: WCLC 2020
- Type: Oral
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 11:45 - 12:45, Scientific Program Auditorium
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OA04.04 - Amivantamab in Post-platinum EGFR Exon 20 Insertion Mutant Non-small Cell Lung Cancer (ID 3031)
11:45 - 12:45 | Author(s): Chee Khoon Lee
- Abstract
- Presentation
Introduction
Despite sharing similar tumor biology to other epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) tumors, no targeted therapies have been approved for NSCLC harboring EGFR Exon 20 insertion mutations (Exon20ins). The standard of care remains platinum-based chemotherapy for the front-line, with no clear subsequent options available. Amivantamab (JNJ-61186372) is a novel, fully human EGFR-MET bispecific antibody with immune cell-directing activity that targets activating and resistance EGFR mutations, as well as MET mutations and amplifications, and has received FDA Breakthrough Therapy Designation for the treatment of patients with EGFR Exon20ins NSCLC after platinum-based chemotherapy. Here we present updated results on the Exon20ins cohort from the CHRYSALIS study (NCT02609776).
Methods
The dose escalation phase enrolled patients with advanced NSCLC to determine the recommended phase 2 dose (RP2D) of 1050 mg (1400 mg for ≥80 kg) amivantamab. The dose expansion phase assessed the safety and efficacy of amivantamab in patients with EGFR- and MET-mutant NSCLC treated at the RP2D. Disease response was assessed by the investigator per RECIST v1.1 and is presented for those patients with Exon20ins NSCLC who had progressed on prior platinum-based chemotherapy, were treated at the RP2D, and had at least 3 post-baseline disease assessments (18 weeks) or discontinued, progressed, or died prior to the 3rd assessment (the Post-Platinum Cohort). The data cutoff date was 8 Jun 2020.
Results
In the Post-Platinum Cohort (n=81), median age was 62 (42 – 84), 59% were women, 49% were Asian, median prior lines of therapy was 2 (1 – 7), and 53% were never-smokers. At a median follow-up of 6.5 months (1.1 – 29.3), investigator-assessed overall response rate (ORR) was 36% (29/81; 95% CI, 25 – 47), with all responders achieving partial response (PR). The clinical benefit rate (≥PR or stable disease ≥11 weeks) was 73% (59/81; 95% CI, 62 – 82). Responses were durable at a median of 6.8 months (95% CI, 5.0 – not reached) with ongoing responses in 18/29 (longest at 16+ months). Median progression-free survival was 8.3 months (95% CI, 5.5 – 12.7) and median overall survival was 22.8 months (95% CI, 14.0 – not reached).
Among all phase 1 patients, across a variety of EGFR genomic alterations and lines of therapy, treated with amivantamab monotherapy at the RP2D (n=258), the most common adverse events (AEs) were rash (78%), infusion related reaction (IRR; 65%), and paronychia (40%). Additional EGFR-related AEs were stomatitis (19%), pruritus (19%), and diarrhea (11%). Grade ≥3 AEs were reported in 39% of patients; 14% were considered treatment-related, with rash (3%) and IRR (2%) being most frequent. No treatment-related deaths were reported. The incidence of treatment-related AEs leading to dose reduction and discontinuation was 10% and 3%, respectively.
Conclusion
Amivantamab treatment led to promising efficacy with durable responses in patients with EGFR Exon20ins NSCLC post-platinum doublet and continues to demonstrate a manageable safety profile in over 250 patients treated at the RP2D. A phase 3 study, PAPILLON, evaluating amivantamab in combination with chemotherapy in the front-line setting is in planning stages.
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P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P76.64 - Alternating Osimertinib and Gefitinib as Second-Line Treatment for EGFR-Mutated NSCLC Harbouring a T790M Resistance Mutation (OSCILLATE) (ID 3282)
00:00 - 00:00 | Author(s): Chee Khoon Lee
- Abstract
Introduction
Osimertinib is standard of care for advanced EGFR-mutated NSCLC following the emergence of T790M resistance mutations, with a median progression-free survival (PFS) of 10 months. Mechanisms of resistance to osimertinib include acquisition of C797S mutations and loss of T790M mutations. We hypothesised that alternating treatment with osimertinib and gefitinib would modulate clonal populations within tumors and delay the emergence of resistance. The aim of this study was to assess the activity, feasibility, and safety of alternating therapy, and to explore plasma ctDNA dynamics and mechanisms of resistance.
Methods
This open label, single-arm, multi-centre, investigator-initiated, phase 2, cooperative group trial included adults with metastatic, EGFR-mutated NSCLC with an acquired, T790M resistance mutation demonstrated in tissue or plasma. Study treatment was osimertinib 80mg daily for 8 weeks, then alternating 4-week cycles of gefitinib 250mg daily and osimertinib 80mg daily, until disease progression. Blood samples for ctDNA were taken on day 1 of each 28-day cycle, and day 15 of cycles 3 and 4. The primary endpoint was PFS at 1 year. Secondary endpoints included feasibility of alternating treatment, time to treatment failure (TTTF), objective tumour response (OTR), overall survival (OS), and adverse events (AE).
Results
We recruited 47 eligible participants from September 2017 to June 2019: 63% female, 55% aged 60 or older; 96% ECOG 0-1; 67% had an exon 19 deletion, 31% had an exon 21 L858R substitution, 4% had an uncommon or compound EFGR mutations; and, 23% had brain/leptomeningeal metastasis. PFS at 1 year was 38% (27% to 55%), median PFS was 9.2 months (7.2 to 13), and median TTTF was 9.4 months (7.6 to 13). The OTRR was 40% (19/47, 95% CI 28 to 55%). Alternating treatment was feasible with only 1 participant discontinuing gefitinib due to treatment side-effects, and only 2 requiring a treatment interruptions within the first 6 months, both for SAEs unrelated to treatment. The most frequent grade 3-4 AE were headache and nausea, each occurring in 2 participants. The one death that occurred during study treatment was due to lung infection and judged unrelated to treatment.
Conclusion
Alternating osimertinib and gefitinib was safe, feasible, and PFS was similar to that of single-agent osimertinib, as second-line treatment for EGFR-mutated NSCLC with a T790M resistance mutation. Analyses of ctDNA levels, dynamics, and mechanisms of resistance are ongoing.
