In a recent interview with PharmaShots, Kiran Patel, Vice President Clinical Development, Solid Tumor Franchise at Janssen shared his views on the regulatory submission of Amivantamab for the Treatment of Patients with Metastatic Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations.

Shots:

• Janssen reported the BLA submission to the US FDA seeking approval of Amivantamab for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations
• The filing is the first regulatory submission for patients with exon 20 insertion mutations and it also marks Janssen's first filing for the treatment of patients with lung cancer
• Amivantamab is an investigational bispecific antibody that targets both a driver mutation as well as a resistance mechanism and has received BTD in March, is being studied as a monothx. & combination therapy in NSCLC with EGFR mutations, including in earlier lines of therapy

Tuba: A quick highlight of clinical data submitted for the BLA submission of Amivantamab to the US FDA?

Kiran: On December 3, 2020, Janssen submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA)  seeking approval of amivantamab for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.

The BLA is supported by data from the monotherapy arm of the Phase 1 CHRYSALIS study, a multi-center, open-label, multi-cohort study. The study evaluated the safety 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.

The submission of this BLA is an important step as we hope to advance a new therapeutic option for patients with NSCLC and exon 20 insertion mutations for whom there are currently no approved targeted therapies. The current standard of care for EGFR Exon 20 insertion mutation-positive NSCLC is chemotherapy.

Tuba: What is the mechanism of action of Amivantamab and how does it work?

Kiran: Amivantamab is an investigational, fully-human, EGFR, and mesenchymal-epithelial transition factor (MET) bispecific duo-body with immune-cell directing activity that targets tumors with activating and resistance EGFR and MET mutations and amplifications. As a monotherapy, amivantamab has shown activity in patients with diverse EGFR mutant disease.

Tuba: Why is Janssen focused on metastatic NSCLC with EGFR exon 20 insertion mutations?

Kiran: Lung cancer is the leading cause of cancer deaths worldwide. In the U.S., lung cancer is the second most common cancer in both men and women, after skin cancer and NSCLC makes up 80 to 85 percent of all lung cancers. EGFR genetic alterations are among the most common driver mutations for NSCLC and are present in 10 to 15 percent of patients with NSCLC. Additionally, EGFR exon 20 insertion mutations identify a distinct subset of lung adenocarcinomas, accounting for at least nine percent of all EGFR mutations.

Currently, there are currently no FDA-approved targeted therapies for patients with NSCLC who have EGFR exon 20 insertion mutations. Given this significant unmet need, we are committed to improving outcomes for patients diagnosed with this complex, deadly disease. Janssen is committed to advancing targeted therapies for patients living with genetically defined lung cancer where there remains a high unmet need for new treatment options.

Tuba: When can we expect approval and launch of amivantamab in the US?

Kiran: The BLA submission was completed on December 3, 2020. In March 2020, amivantamab received FDA Breakthrough Therapy Designation, which is granted to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition. We do not speculate on potential approval timelines.

Tuba: When can we expect results from the CHRYSALIS combination arm?

Kiran: We presented interim data from the CHRYSALIS combination arm at the ESMO 2020 Virtual Congress in September. Data showed the combination of amivantamab and lazertinib achieved a 100 percent overall response rate in the cohort of patients with treatment-naïve EGFR-mutated NSCLC. We look forward to the continued evaluation of amivantamab in combination with lazertinib in EGFR mutation-positive NSCLC patients.

Tuba: How many patients have been part of the expanded access program (EAP) in the US?

Kiran: Jansen established an expanded access program (EAP) for EGFR Exon 20 insertion patients in the U.S. who may be eligible to obtain access to amivantamab during review of the BLA. For information about Janssen's pre-approval access program, visit https://www.janssen.com/compassionate-use-pre-approval-access. We cannot disclose patient enrollment numbers for the EAP.

Tuba: Has Janssen started any HCP awareness, HCP education, and patient support and awareness programs?

Kiran: We recently launched a website, Hidden EGFR Threats, intended to inform physicians and patients about the multiple threats of EGFR-mutated advanced NSCLC.

Tuba: Is Janssen planning to assess amivantamab in other indications?

Kiran: The results from the CHRYSALIS study have led to new studies to further evaluate the potential of amivantamab and lazertinib combination therapy. The Phase 3 MARIPOSA study will compare amivantamab in combination with lazertinib with osimertinib in untreated advanced EGFR-mutated NSCLC, and a Phase 2 trial, CHRYSALIS-2 is ongoing and enrolling patients who have progressed after treatment with osimertinib and chemotherapy.

Tuba: Any near-future plans to file for EU or any other geographies?

Kiran: We have plans to pursue approval of amivantamab in other markets with the goal of bringing this novel therapy to patients around the world who may benefit, but it is premature to speculate about timing.

Image Source: Medical Forum

About Author:

Kiran Patel is a Vice President of Clinical Development, Solid Tumor Franchise at Janssen and is serving Janssen since 2015.

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