1247P - Management of infusion-related reactions (IRRs) in patients receiving amivantamab

Background Amivantamab, an epidermal growth factor receptor (EGFR)-MET bispecific antibody, has shown antitumor activity in diverse EGFR and MET-driven non-small cell lung cancer (NSCLC), with safety consistent with associated on-target activities. IRRs are characteristic of antibody infusions, and have been described for other therapeutic antibodies. We review IRR and its management in patients (pts) treated with amivantamab. Methods CHRYSALIS is an ongoing phase I dose escalation/expansion study of amivantamab in advanced EGFR mutant NSCLC (NCT02609776). This report includes pts treated at the recommended phase II dose (RP2D) of 1050 mg IV amivantamab (1400 mg, ≥80 kg). Mitigations for IRR included split first dose (350 mg on day 1, remainder on day 2), reduced initial infusion rates with proactive infusion interruption, and required steroid premedication for the initial dose. For all doses, pre-infusion antihistamines and antipyretics were required; steroids were optional after initial dose. Results As of 8 Jun 2020, 258 pts have received amivantamab at the RP2D. IRR was reported in 167 pts (65%) and was characterized by dyspnea, flushing, chills, and nausea. IRR severity was mostly grade 1–2; grade 3 IRR occurred in 5 pts, and 1 had a grade 4 event. Median time to IRR onset was 44 mins, with 94% occurring on cycle 1, day 1 (C1D1); only 1 event occurred ≥C2. Of the 167 pts with IRR, 134 completed the full split dose and continued treatment per schedule; 33 pts (13%) aborted C1D1 infusion due to IRR, of which 4 discontinued further therapy. Per protocol, IRRs were mitigated on C1D1 with holding of infusion (54%) and reinitiating at a reduced rate (50%). Translational studies in a subset of pts measuring 22 circulating analytes (e.g., markers of cytokine release syndrome, mast cell degranulation, tumor lysis syndrome, complement activation) failed to distinguish a pattern between pts with and without IRR. Conclusions IRRs with amivantamab treatment were frequently observed but were mostly low grade, primarily limited to the first infusion, and rarely occurred with subsequent dosing. Close monitoring for IRR with the initial dose helps mitigate IRR through proactive rate modifications. Clinical trial identification NCT02609776

1193MO - Amivantamab plus lazertinib in post-osimertinib, post-platinum chemotherapy EGFR-mutant non-small cell lung cancer (NSCLC): Preliminary results from CHRYSALIS-2

Background The combination of amivantamab (ami), an epidermal growth factor receptor (EGFR)-MET bispecific antibody, with the 3rd-generation tyrosine kinase inhibitor lazertinib (laz), yielded a 36% overall response rate (ORR) in the post-osimertinib (osi), chemotherapy-naïve setting (Cho Ann Oncol 2020;31:S813, Oral 1258). The activity of ami + laz after progression on both osi and platinum doublet chemotherapy is unknown. Methods CHRYSALIS-2 (NCT04077463) is an ongoing open-label study that includes a single-arm cohort (Cohort A) examining ami + laz in patients (pts) with EGFR Exon19del or L858R NSCLC whose disease progressed after standard of care osi and platinum chemotherapy (3rd / 4th line; “target” population) and in more heavily-pretreated (5th line +) pts. Pts received the established recommended combination dose of 1050 mg IV ami (1400 mg, ≥80 kg) + 240 mg oral laz. Investigator-assessed response per RECIST v1.1 is reported for pts with ≥2 post-baseline disease assessments. Results As of 19 Apr 2021, 116 pts were enrolled in Cohort A (median 63 y, 68% women, 60% Asian, median of 3 [range, 2–14] prior lines), with 59 in the target and 57 in the heavily-pretreated populations. Of 28 response-evaluable pts in the target population, 12 (43% [95% CI, 24–63]) reported partial response (PR) as best response; of the 12 responses, 9 were confirmed (3 pending), for an overall response rate (ORR) of 32% (95% CI, 16–52). Of 45 pts in the heavily-pretreated population, 7 reported best response of PR, of which 6 were confirmed (1 pending), for an ORR of 13% (95% CI, 5–27). At 3.7-mo median follow-up, 17 pts in the target population remain on treatment: 10 with PR (3 pending confirmation) and 7 with stable disease. The safety profile for Cohort A was consistent with previously reported experience with ami + laz at the recommended combination dose, and no new safety signals were identified. Conclusions Ami + laz is showing encouraging early activity in a population that progressed on both standard of care osi and platinum chemotherapy. Activity is consistent with the post-osi population, suggesting intervening chemotherapy does not impact ami + laz activity. Clinical trial identification NCT04077463