Virtual Library
Start Your Search
Jong-Seok Lee
Author of
-
+
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
-
+
OA04.04 - Amivantamab in Post-platinum EGFR Exon 20 Insertion Mutant Non-small Cell Lung Cancer (ID 3031)
11:45 - 12:45 | Author(s): Jong-Seok 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.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
P85 - Targeted Therapy - Clinically Focused - MET (ID 262)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
-
+
P85.01 - Activity of Tepotinib in Brain Metastases (BM): Preclinical and Clinical Data in MET Exon 14 (METex14) Skipping NSCLC (ID 1785)
00:00 - 00:00 | Author(s): Jong-Seok Lee
- Abstract
Introduction
Approximately 20% of METex14 skipping NSCLC cases involve brain lesions at diagnosis. Tepotinib is an oral, once-daily, highly selective MET inhibitor that has shown clinical activity in MET-driven tumors. We investigated the activity of tepotinib in preclinical models and patients with baseline BM in the Phase II VISION study.
Methods
Brain penetration was assessed in Wistar rats (n=3) at tepotinib dose 3.66 mg/kg/h intravenously by determining unbound brain (fu br) and plasma (fu pl) concentrations using liquid chromatography with tandem mass spectrometry.
Preclinical efficacy was assessed in two patient-derived xenografts (PDX) obtained from BM harboring high MET amplification (MET copy number gain: 11 for LU5349 and 24 for LU5406). NOD-SCID mice with PDX orthotopically implanted into the brain (n=10/group) were treated with tepotinib 125 mg/kg or vehicle control orally once daily. Intracranial tumor growth was monitored by gadolinium-based MRI.
Patients enrolled in VISION Cohort A with METex14 skipping NSCLC and asymptomatic BM (prior brain-specific therapy allowed) received tepotinib 500 mg once daily. Endpoints included systemic response per RECIST v1.1, duration of response (DOR), and progression-free survival (PFS) by independent review committee (IRC).
Results
The fraction of unbound tepotinib in rat brain tissue (fu br = 0.4%) was low compared with plasma (fu pl = 4%), indicating high binding in the brain. Upon treatment with tepotinib, both PDX tumors from MET-driven NSCLC BM regressed significantly in orthotopic brain models (mean tumor volume reduction of 63% for LU5406 and 84% for LU5349).
VISION Cohort A enrolled 22 patients with baseline BM (identified by IRC or investigator assessment), whose demographic characteristics were similar to the overall population (N=152).
As of July 1, 2020, 21 patients with baseline BM had ≥9 months’ follow-up and were included in efficacy analyses. Confirmed systemic best overall response was partial response in 11 patients for an ORR (95% confidence interval [CI]) of 52.4% (29.8, 74.3), which was comparable to that in overall population (table). Median DOR (95% CI) was 9.5 months (5.5, not estimable), and median PFS (95% CI) was 9.5 months (5.7, 11.2). Case studies illustrating response of brain lesions in VISION patients will also be presented.
Patients with baseline brain metastases (n=21) Overall (N=146)
Systemic objective response rate, % (95% CI)
52.4 (29.8, 74.3)
45.2 (37.0, 53.6)
Disease control rate, % (95% CI)
76.2 (52.8, 91.8)
69.9 (61.7, 77.2)
Best overall response, n (%) Complete response 0 0 Partial response 11 (52.4) 66 (45.2) Stable disease 5 (23.8) 36 (24.7)
Conclusion
Tepotinib administration resulted in regression of orthotopic BM in preclinical models. Patients in the VISION study with baseline BM had a comparable systemic response to that in the overall population. Tepotinib activity against BM will be further assessed by follow-up brain scans in the confirmatory VISION Cohort C.
