medwireNews: Fresh findings from the phase 1 CHRYSALIS and CHRYSALIS-2 trials have been presented at the 2022 ASCO Annual Meeting in Chicago, Illinois, USA, adding support for the use of amivantamab in certain groups of patients with advanced non-small-cell lung cancer (NSCLC).
Catherine Shu (Columbia University Medical Center, New York, USA) gave an update from the CHRYSALIS-2 study assessing the bispecific antibody targeting MET and EGFR given in combination with the third-generation EGFR–tyrosine kinase inhibitor (TKI) lazertinib for patients with disease progression after receiving osimertinib and platinum-based chemotherapy.
The combination “represents a chemotherapy-free regimen” for this heavily treated patient population, the presenter observed.
Amivantamab was given at a weekly dose of 1050 mg (bodyweight <80 kg) or 1400 mg (≥80 kg) for the 4-week cycle and twice weekly thereafter alongside lazertinib 240 mg/day.
The objective response rate (ORR) was 33% for the full population of 162 patients, including a complete response in 1%, and the clinical benefit rate was 57%, with a median duration of response of 9.6 months. Of the 54 patients with a response, 30 remained on treatment at data cutoff and 27 had responded for at least 6 months, the presenter noted.
Shu said the response to amivantamab plus lazertinib was “consistent” across patient subgroups including those with exon 19 deletion versus exon 21 L858R mutation.
She explained that the patient population comprised those who had received first-line osimertinib then chemotherapy (23%), an earlier generation of EGFR–TKI then chemotherapy following osimertinib (42%), or a different sequence and/or multiple treatments (35%). The ORRs for these three subgroups were 21%, 36%, and 39%, respectively.
Moreover, the “durable” activity of the combination in patients given osimertinib plus chemotherapy is comparable to that previously seen in patients who have received only osimertinib, indicating that “intervening chemotherapy does not impact amivantamab plus lazertinib activity,” commented Shu.
She said that the phase 3 MARIPOSA and MARIPOSA-2 trials are now investigating amivantamab plus lazertinib as a first-line regimen. and in combination with carboplatin plus pemetrexed after osimertinib, respectively.
A second update on the use of amivantamab in advanced NSCLC was also presented at the meeting by CHRYSALIS author Matthew Krebs (University of Manchester, UK).
Acknowledging that amivantamab has a higher affinity to MET than EGFR, the researchers assessed the antibody as a monotherapy in a cohort of 55 patients with a primary MET exon 14 skipping mutation (METex14).
The patients were aged a median of 70 years and 58% were women, reflecting the demographics of NSCLC patients with METex14 mutations, while 53% were nonsmokers, 51% were Asian and 18% had a history of brain metastases, the presenter said.
Furthermore, this group comprised nine treatment-naïve individuals, 18 who had received a median 1.5 lines of prior treatment not including a MET–TKI, and 28 who had received a median 3.0 lines of treatment that included the MET–TKIs tepotinib or capmatinib.
The ORR was 33% among 46 evaluable patients overall but varied by subgroup at 57% for treatment-naïve patients, 47% patients pretreated without a MET–TKI, and 17% for those who had previously received a MET–TKI.
These responses were both “early” and “durable,” Krebs said, noting that they occurred after a median of 1.6 months of treatment and with an unreached median duration. Ongoing responses were reported for 11 of the 15 patients and 10 patients had responded for 6 months or longer.
The presenter described the adverse event profile for amivantamab as being “consistent” with that expected for on-target inhibition of MET and EGFR, and generally affecting patients at grade 1 or 2. The predominant side effect was infusion-related reactions, affecting 69%, but just 5% of patients experienced this at grade 3 or higher, and these reactions were “very rarely” seen after the first day of cycle 1, he emphasized.
Krebs concluded that the current findings in METex14 patients and the earlier CHRYSALIS results for patients with EGFR-driven exon 20 insertion mutations mean that the “independent, targeting action of each arm of the bispecific antibody” has now been confirmed.
Nevertheless, he added that the CHRYSALIS trial is continuing to enroll patients to the METex14 arm of the study.
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