Janssen Announces Phase 1 Results for Amivantamab for Advanced NSCLC

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 mesenchymal epithelial transition factor (MET) bispecific antibody, which targets activating and resistant EGFR and MET mutations and amplifications. Investigators assessed efficacy using overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) and 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, multicenter study evaluating the safety, pharmacokinetics and efficacy of amivantamab as a monotherapy and in combination with lazertinibi, 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.

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). The current standard of care for this patient population is conventional chemotherapy.6 Currently, there are no FDA-approved targeted therapies for patients with lung cancer who have EGFR Exon 20 insertion mutations.7 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 Hematology-Oncology, Department of Medicine, Samsung Medical Center, 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."

An ORR of 36 percent (95 percent CI, 21–53) was observed in all patients and 41 percent (95 percent CI, 24–61) in patients previously treated with platinum-based chemotherapy.2 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 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 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. Tumor 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. IRR occurred predominantly on the first infusion and did not prevent subsequent treatments. No Grade ≥3 rash was reported, and one patient reported Grade 3 diarrhea (six percent had diarrhea of any Grade). Six percent of patients had treatment-related grade ≥3 AEs of hyperamylasemia, hypokalemia, 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.

"Despite advances in the treatment of patients with lung cancer, there remains a need to develop new therapies for patients diagnosed with non-small cell lung cancer with EGFR Exon 20 mutations," said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Janssen Research & Development, LLC. "We are pleased to present these initial results for amivantamab and are committed to the development of novel targeted therapies to address unmet needs for these patients who unfortunately have high rates of morbidity and mortality."

Amivantamab (JNJ-6372) is an investigational EGFR-MET bispecific antibody with immune cell-directing activity that targets activating and resistant EGFR and MET mutations and amplifications. The production and development of the antibody followed Janssen Biotech Inc.'s licensing agreement with Genmab for use of its DuoBody® technology platform.

Worldwide, lung cancer is the most common cancer and NSCLC makes up 80-85 percent of all lung cancers. The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma. Among the most common driver mutations in NSCLC, are alterations in EGFR, which is a receptor tyrosine kinase that helps cells grow and divide. EGFR mutations are present in 10 to 15 percent of patients with NSCLC and occur in 40 to 50 percent of Asian patients who have NSCLC adenocarcinoma. EGFR Exon 20 insertion mutations identify a distinct subset of lung adenocarcinomas, accounting for at least nine percent of all EGFR mutations. The five-year survival rate for patients with metastatic NSCLC is currently six percent.