▎WuXi AppTec Content Team Report

On October 31, the official website of the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China announced,Johnson & JohnsonAmivantamab (Evusheld) Subcutaneous InjectionTwo new indications have been approved for clinical trials, with the proposed indications including: in combination with FOLFIRI forAfter systematic treatmentRAS/RAFWild-type, Recurrent Metastatic Colorectal Cancer; Combined with mFOLFOX6 or FOLFIRI forRAS/RAFWild-type, Left-sided, Unresectable or Metastatic Colorectal Cancer。

Screenshot source:CDE Official Website

AmivantamabIt is an investigational fully human bispecific antibody targeting EGFR and MET.In addition to blocking EGFR and MET-mediated signal transduction, it can also direct immune cells to target those with activating and resistantEGFR/METTumors with Mutations and Amplifications。Public information shows that AmivantamabInjectable FormulationsIt received accelerated approval from the FDA as early as May 2021, and since then has been approved for multiple indications, covering patients with different types of non-small cell lung cancer.AmivantamabSubcutaneous Injection FormulationThe listing applications were also successively approved in June and September this year.FDAAndNMPAAcceptance，CanFor all currently approved or submittedAmivantamabIndications for Intravenous Preparations。

In view ofMETAmplification is associated with resistance to anti-EGFR therapy in metastatic colorectal cancer (mCRC). Therefore, the researchers believe,Amivantamab, as a dual co-inhibitor of EGFR and MET, can improve the prognosis of recurrent/refractory mCRC.. Consequently, Johnson & Johnson had previously initiated a Phase 1/2 clinical study named OrigAMI-1 to evaluate the safety and efficacy of amivantamab as a monotherapy for patients with refractory mCRC.

Through ctDNA testing, eligible patients areKRAS、NRAS、BRAFAndEGFRExtraterritorial wild type, noneERBB2/HER2Amplification. Among them,Cohorts A and B were previouslyLeft-sided mCRC patients with no/prior exposure to anti-EGFR monoclonal antibodies, cohort C consists of right-sided mCRC patients (regardless of prior treatment).Anti-EGFR Therapy)。

According to the researchers at2024 ASCO Gastrointestinal Cancers Symposium (2024 ASCO GI)Data published onAThe disease control rates (DCR) for groups A, B, and C were 88.2%, 72.2%, and 77.8%, respectively.The median duration of response (mDoR) for confirmed responders in Groups A and B was 7.5 months and 7.4 months, respectively, and treatment is still ongoing for responders in Cohort C. Preliminary biomarker data suggest that amivantamab may have activity in alterations associated with resistance to anti-EGFR antibodies (e.g.,EML4-ALKIntegration,PTEN). The study did not observe any new safety signals.

At the ESMO Congress, Johnson & Johnson announcedUpdated data of OrigAMI-1,Amivantamab + FOLFOX or FOLFIRI 1L or 2L TreatmentRAS/BRAFPatients with wild-type mCRC still demonstrated promising antitumor activity.The overall ORR was 49%, and the DCR was 88%.. The researchers also observed clinically significantIntrahepatic anti-tumor activity, intrahepatic ORR of 53%, intrahepatic DCR of 93%。Notably, due to the product's significant anti-tumor activity, 21% of patients were able to undergo radical surgery.

▲OrigAMI-1 Study Results (Screenshot Source: Johnson & Johnson Official Website)

According to a previous press release from Johnson & Johnson, the evaluation is based on a pivotal phase 3 registration trial of the amivantamab regimen as a first-line and second-line treatment for colorectal cancer (OrigAMI-2、OrigAMI-3）It is currently in the planning stage. The Phase 3 clinical trialPlan to use more convenient administrationAmivantamabTheSubcutaneous injection formulation.The patient was able to complete the injection of the subcutaneous formulation within 5 minutes.Significantly shorten the administration time。

The approval of this subcutaneous injection formulation of Amivantamab for a new clinical study marks that the product is about to carry out clinical research on colorectal cancer in China.

[1] Official of the Center for Drug Evaluation, National Medical Products Administration of ChinaWebsite. Retrieved Nov 1, 2024, from https://www.cde.org.cn/main/xxgk/listpage/da6efd086c099b7fc949121166f0130c

[2]Amivantamab monotherapy in relapsed/refractory metastatic colorectal cancer: OrigAMI-1, an open-label, phase 1b/2 study. Retrieved Jan 22, 2024, from https://ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.135

[3]Amivantamab plus FOLFOX or FOLFIRI in metastatic colorectal cancer Results from OrigAMI-1, a phase 1b/2 study.  from  https://www.janssenscience.com/media/attestation/congresses/oncology/2024/esmo/amivantamab-plus-folfox-or-folfiri-in-metastatic-colorectal-cancer-results-from-origami1-a-phase.pdf