SC evantumumab/Carestream is consistent with intravenous formulations for EGFR mutated non-small cell lung cancer

Based on PAOMA-2 published in2025 Results of Cohort 5 of the Phase 3 trial (NCT05498428), Lazertinib (Lazertinib) combination treatment for EGFR mutated non-small cell lung cancer (NSCLC) patients, the first subcutaneous injection of amivantamab(amivantamab) showed efficacy comparable to intravenous injection of amivantamab.

Among all patients (n=75) who received subcutaneous evantumumab, after a median follow-up of 6.5 months, the objective response rate (ORR) was 82% (95% CI, 71%-90%) by investigator assessment and 87% (95% CI, 77%-94%) by independent review committee (IRC). The results were consistent with the published phase 3 MARIPOSA trial (NCT04487080), which showed a blinded IRC ORR of 86% (95% CI, 83%-89%) for intravenous evantumumab.

Additionally, the confirmed ORR for the subcutaneous formulation was 79% (95% CI, 69%-88%) and 83% (95% CI, 73%-91%) per investigator and perIRC, respectively. The confirmed clinical benefit rate (CBR) was 97% (95% CI, 91%-100%) according to the investigator's assessment and 96% (95% CI, 89%-99%) according to the IRC.

Among responders to the PALOMA-2 trial, the median time to response was 8.1 weeks (range, 7.0-16.5), the median duration of response (DOR) was not reached, and 93% of responses were ongoing. Furthermore, the median progression-free survival (PFS) and overall survival (OS) were not reached. Response rates for patients who received first-line evantumumab subcutaneously every 4 weeks were consistent with those who received the MARIPOSA regimen.

Investigators in the phase 3 PALOMA-2 trial enrolled patients with treatment-naïve, locally advanced or metastatic NSCLC with documented EGFR exon 19 deletions or L858R mutations and an ECOG performance score of 0 or 1. They are allowed if patients with brain metastases are stable.

If the patient’s weight in the first cycle isIf the patient weighs 80 kg or more, they will receive 1600 mg or 2240 mg of evantumuzumab subcutaneously as an abdominal injection, and if the patient weighs 80 kg or more every 4 weeks thereafter, they will receive 3520 mg or 4640 mg of evantumuzumab subcutaneously. Lanzutinib is taken orally at a dose of 240 mg per day.

The median age was 63 years (range 31-80 years), and the majority of patients were female (68%) and Asian (62%). A total of 68% of patients had an ECOG performance score of 1, 32% had a smoking history, and 43% had brain metastases. Additionally, 60% and 40% of patients had exon 19 deletions and L858R mutations, and all patients had adenocarcinoma histology.

The primary endpoint of the trial is each investigator's ORR assessment. Secondary endpoints include ORR, DOR, response time, CBR, PFS, OS, safety and pharmacokinetics of IRC.

The most common treatment-emergent adverse reactions (TEAE) are related to EGFR/MET. The most common TEAEs of any grade associated with EGFR inhibition included paronychia (any grade, 73%; grade 3 or higher, 5%), rash (58% vs. 12%), acneiform dermatitis (40% vs. 8%), stomatitis (38% vs. 4%), pruritus (34% vs. 1%), and diarrhea (29% vs. 3%). The most common TEAEs related to MET inhibition included hypoalbuminemia (64% vs. 5%) and peripheral edema (36% vs. 0%).

Treatment-related adverse events occurred in 8% of patients that resulted in discontinuation of all study treatments, and the use of PALOMA-2 is not recommended for the prevention of dermatological adverse events. Additionally, 12% (9 of 77) of patients experienced an ARR, 78% (7 of 9) of which occurred during the first dose.

In addition,Venous thromboembolism (VTE) occurred in 13% of patients, including 10% (7 of 67) of patients who received prophylactic anticoagulation and 30% (3 of 10) of patients who did not receive anticoagulation. There were no VTE events resulting in dose interruption, dose reduction, or death. One serious bleeding incident was reported.

Reference materials:https://www.cancernetwork.com/view/sc-amivantamab-consistent-with-iv-formulation-in-egfr-mutated-nsclc