US FDA Approves J&J’s Rybrevant Plus Standard of Care as First and Only Targeted Regimen

US FDA Approves J&J’s Rybrevant Plus Standard of Care as First and Only Targeted Regimen

By, Admin 23 September 2024

US FDA approves J&J’s Rybrevant plus standard of care as first and only targeted regimen to cut risk of disease progression by more than half in second-line EGFR-mutated advanced lung cancer

Overview 

Johnson & Johnson (J&J) announced that the US Food and Drug Administration (FDA) approved Rybrevant (amivantamab-vmjw) in combination with standard of care chemotherapy (carboplatin and pemetrexed) for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations, whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor (TKI).

Words from Cancer Care Centers of Brevard

  • Rybrevant plus chemotherapy may address the most common mechanisms of treatment resistance to third generation EGFR TKIs, such as osimertinib, in the first line,” said Martin Dietrich, M.D., Ph.D., Oncologist, Cancer Care Centers of Brevard. 
  • This multitargeted combination extended progression-free survival and improved overall response compared to chemotherapy alone, offering an important and effective new second-line option for patients.

Survival Rate & Outcomes

  • The five-year survival rate is less than 20 percent for all people with advanced EGFR-mutated NSCLC. 
  • Acquired resistance mechanisms after TKI monotherapy are diverse and polyclonal, making targeted therapy at progression more difficult, thus limiting the efficacy of targeted therapies at progression. 
  • Adding immunotherapy to chemotherapy has also failed to demonstrate clinically meaningful improvements.

Words from the CEO: LUNGevity Foundation

  • The progression-free survival benefits seen in the MARIPOSA-2 study are exciting,” said Andrea Ferris, president and CEO, LUNGevity Foundation. 
  • It is good to see new therapeutic options like the combination of Rybrevant and chemotherapy helping to address unmet needs impacting individuals with EGFR-mutated lung cancer, with the potential for positive change, which gives hope to more patients and their families.

Behind the FDA Approval

  • The FDA approval is based on results from the phase 3 MARIPOSA-2 (NCT04988295) study evaluating the efficacy and safety of Rybrevant in combination with chemotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR ex19del or L858R substitution mutations after disease progression on or after osimertinib.
  • Results showed Rybrevant plus chemotherapy reduced the risk of disease progression or death (progression-free survival [PFS]) by 52 per cent vs. chemotherapy alone, the study’s primary endpoint. 
  • The median PFS for patients receiving Rybrevant plus chemotherapy was 6.3 months, compared to 4.2 months for chemotherapy alone. 
  • Additionally, Rybrevant plus chemotherapy showed a confirmed overall response rate (ORR) of 53 per cent compared to 29 per cent with chemotherapy alone.

Rybrevant with Chemotherapy

Amivantamab-vmjw (Rybrevant) in combination with chemotherapy is the only National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) Category 1 treatment option for patients with EGFR-mutated NSCLC progressing on osimertinib who are symptomatic with multiple lesions.

Statement from J & J Innovative Medicine

  • This milestone reinforces Rybrevant as an important treatment option for patients with EGFR-mutated NSCLC who continue to face high unmet needs after disease progression on or after TKI therapy,” said Kiran Patel, M.D., vice president, clinical development, solid tumours, Johnson & Johnson Innovative Medicine. 
  • Patients need and deserve effective, targeted approaches across all lines of therapy. With Rybrevant-based regimens, we are bringing potential new standards of care to the nearly 30,000 patients diagnosed with EGFR-mutated NSCLC in the United States each year.

Safety Profile

  • The safety profile of Rybrevant in combination with chemotherapy was consistent with the established profiles of the individual treatments. 
  • Permanent discontinuation of Rybrevant due to adverse reactions occurred in 11 per cent of patients.

MARIPOSA-2 Results

Results from MARIPOSA-2 were first presented in a Presidential Symposium at the European Society of Medical Oncology (ESMO) 2023 Congress (Abstract #LBA15) and simultaneously published in the Annals of Oncology.

3rd Indication for Rybrevant

This approval marks the third new indication for Rybrevant this year, following the August 20, 2024, US FDA approval announcement of Rybrevant in combination with Lazcluze (lazertinib) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, based on the phase 3 MARIPOSA study, and the March 1, 2024, US FDA approval announcement of Rybrevant in combination with chemotherapy (carboplatin-pemetrexed) for the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, based on the phase 3 PAPILLON study.

Submission of BLA to USFDA

  • On June 17, 2024, Johnson & Johnson also announced the submission of a Biologics License Application to the US FDA for a fixed combination of amivantamab and recombinant human hyaluronidase for subcutaneous administration (SC amivantamab) for all currently approved or submitted indications of intravenous (IV) Rybrevant. 
  • This application is based on the phase 3 PALOMA-3 study, with preliminary results which showed a five-fold reduction in infusion-related reactions (IRR) with a five-minute administration of SC amivantamab. 
  • Longer overall survival (OS), PFS and duration of response (DOR) were also observed with SC amivantamab. 
  • On August 14, 2024, the US FDA designated this application for Priority Review.

About MARIPOSA-2 Trial

  • MARIPOSA-2 (NCT04988295), which enrolled 657 patients, is a randomized, open-label phase 3 study evaluating the efficacy and safety of two combination regimens of Rybrevant (with and without Lazcluze) and chemotherapy. 
  • Patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC who had disease progression on or after treatment with osimertinib were randomized to treatment with Rybrevant plus chemotherapy, Rybrevant plus chemotherapy with Lazcluze or chemotherapy alone.
  • The dual primary endpoint was used to compare the PFS (using RECIST v1.1 guidelines§) as assessed by blinded independent central review (BICR) for each experimental arm to chemotherapy alone. 
  • Secondary endpoints included objective response as assessed by BICR, OS, DOR, time to subsequent therapy, PFS2 and intracranial PFS.

Rybrevant Antibody

  • Rybrevant (amivantamab-vmjw), a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity, is approved in the US, Europe, and in other markets around the world as monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. 
  • In the subcutaneous formulation, amivantamab is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s Enhanze drug delivery technology.

Rybrevant Approval

  • Rybrevant is approved in the US, Europe, and in other markets around the world in combination with chemotherapy (carboplatin and pemetrexed) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test.
  • Rybrevant is approved in the US in combination with Lazcluze (lazertinib) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, as detected by an FDA-approved test. 
  • A marketing authorization application (MAA) and type II extension of indication application were submitted to the EMA seeking approval of Lazcluze in combination with Rybrevant based on the MARIPOSA study.

Submission of sBLA to FDA

  • In November 2023, Johnson & Johnson submitted a supplemental Biologics License Application (sBLA) to the US FDA for Rybrevant in combination with chemotherapy for the treatment of patients with EGFR-mutated NSCLC who progressed on or after osimertinib based on the MARIPOSA-2 study. This indication was approved in Europe in August 2024.
  • In June 2024, Johnson & Johnson submitted a BLA to the US FDA for the subcutaneous formulation of Rybrevant in combination with Lazcluze for all currently approved or submitted indications of IV Rybrevant in certain patients with NSCLC. In August 2024, the US FDA designated this application for Priority Review.

J&J Assistance for Patient

  • J&J offers comprehensive access and support information and resources to assist patients in gaining access to Rybrevant. 
  • Our patient support programme, J&J withMe, is available to provide personalized support to help patients start and stay on their J&J medicines. 
  • J&J withMe offers providers help supporting their patients by verifying patients' insurance coverage, providing information on Prior Authorization and Appeals processes and educating on reimbursement processes. 
  • Patients can connect to Rybrevant withMe to receive cost support, regardless of insurance type, free, personalized one-on-one support from a Care Navigator, and resources and community connections.

About lung Cancer

  • Worldwide, lung cancer is one of the most common cancers, with NSCLC making up 80 to 85 per cent of all lung cancer cases.  
  • The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma. 
  • Amog the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division. 
  • EGFR mutations are present in 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 per cent of Asian patients.  
  • EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations. 
  • The five-year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR tyrosine kinase inhibitors (TKIs) is less than 20 percent. 
  • EGFR exon 20 insertion mutations are the third most prevalent activating EGFR mutation. 
  • Patients with EGFR exon 20 insertion mutations have a real-world five-year OS of eight percent in the frontline setting, which is worse than patients with EGFR ex19del or L858R mutations, who have a real-world five-year OS of 19 per cent.

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