Janssen announces phase 1 results for amivantamab in advanced NSCLC harbouring Exon 20 insertion mutations

The Janssen Pharmaceutical Companies of Johnson & Johnson announced results from the Phase 1 CHRYSALIS study evaluating amivantamab (JNJ-6372) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) Exon 20 insertion mutations. Amivantamab is an EGFR and MET-targeted bispecific antibody, which targets activating and resistance EGFR mutations, and MET pathway activation. Investigators assessed efficacy using overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), duration of response, as well as the safety profile of amivantamab, which were the basis of the U.S. Food and Drug Administration (FDA) Breakthrough Therapy Designation granted earlier this year.

The Phase 1 CHRYSALIS study is a first-in-human, open-label, multi-cohort, multicentre study evaluating the safety, pharmacokinetics and efficacy of amivantamab as a monotherapy and in combination with lazertinib, a novel third-generation EGFR tyrosine kinase inhibitor (TKI), in adult patients with advanced NSCLC. Fifty patients with EGFR Exon 20 insertion-mutated NSCLC received the recommended Phase 2 dose (RP2D) of amivantamab. Among these 50 patients, 39 were evaluable for response with 13 distinct EGFR Exon 20 insertion mutations identified. Detailed results will be presented as a poster presentation and discussion at the American Society of Clinical Oncology (ASCO) Virtual Scientific Programme beginning Friday 29th May.

Patients with NSCLC and EGFR Exon 20 insertion mutations have a form of disease that is generally insensitive to approved EGFR TKI treatments and as a result carries a worse prognosis compared to patients with more common EGFR mutations (Exon 19 deletions/L858R substitution). Currently, there are no targeted therapies approved specifically for patients with lung cancer who have EGFR Exon 20 insertion mutations. Estimated median overall survival for patients with NSCLC and Exon 20 insertion mutations is 16 months.

“Lung cancer is the leading cause of cancer deaths worldwide, and genetic factors such as EGFR mutations can have a significant impact on the development and progression of non-small cell lung cancer,” said Keunchil Park, M.D., Ph.D., Professor, Division of Haematology-Oncology, Department of Medicine, Samsung Medical Centre, Sungkyunkwan University School of Medicine in Seoul, South Korea, and lead study investigator. “We look forward to sharing these data that provide initial insights into the potential of amivantamab as a treatment option for patients with non-small cell lung cancer and EGFR Exon 20 insertion mutations who have a high unmet need and often do not respond to the current standard of care.”

Findings from the study showed an ORR of 36 percent (95 percent CI, 21–53) in all evaluable patients and 41 percent (95 percent CI, 24–61) in the 29 evaluable patients previously treated with platinum-based chemotherapy. Additionally, the median duration of response for all evaluable patients was 10 months and seven months for patients previously treated with platinum-based chemotherapy. The median progression-free survival was 8.3 months (95 percent CI, 3.0–14.8) for all evaluable patients and 8.6 months (95 percent CI, 3.7–14.8) for patients previously treated with platinum-based chemotherapy. The clinical benefit rate (partial response or better or stable disease of at least 12 weeks [two disease assessments]) was 67 percent (95 percent CI, 50–81) for all evaluable patients and 72 percent (95 percent CI, 53–87) for patients previously treated with platinum-based chemotherapy. Responses were observed in both treatment-naive patients and those previously treated with platinum-based chemotherapy. Tumour responses were most frequently observed at the first disease assessment after starting therapy.

The most common all-grade adverse events (AE) were rash, infusion-related reaction (IRR), and paronychia. IRRs occurred predominantly on the first infusion and did not prevent subsequent treatments.1 No grade ≥3 rash was reported, and one patient reported grade 3 diarrhoea and six percent had diarrhoea of any grade. Six percent had treatment-related grade ≥3 AEs of hyperamylasaemia, hypokalaemia, increased lipase and shoulder/chest pain. Treatment-related serious AEs of cellulitis, interstitial lung disease and shoulder/chest pain were reported in six percent of patients. Additional EGFR-related AEs included stomatitis (sixteen percent), pruritus (fourteen percent), and diarrhoea (six percent).

“Despite years of research and the availability of more treatment options, lung cancer remains Europe’s biggest cancer death threat,” said Dr Joaquín Casariego, M.D., Janssen Therapeutic Area Lead Oncology for Europe, Middle East & Africa, Janssen-Cilag S.A. “It is vital that we develop new, innovative, targeted treatments to improve outcomes for patients with this aggressive cancer. The initial data presented today provides encouraging insights on the potential of amivantamab in non-small cell lung cancer bearing Exon 20 insertion mutations, and we are committed to exploring further the role this innovation may have in addressing the unmet needs for many more patients, their families and the medical community.”