American Association for Cancer Research Annual Meeting

American Association for Cancer Research Annual Meeting

Perspective from Nicholas Rohs, MD
Disclosures: Garon reports financial relationships with AstraZeneca, Bristol-Myers Squibb, Dracen, Dynavax, Eli Lilly, EMD Serono, Genentech, Iovance, Merck, Mirati, Neon and Novartis. Please see the abstract for all other researchers’ relevant financial disclosures.
April 29, 2020
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Capmatinib shows efficacy in lung cancer subset, including patients with brain metastases

Perspective from Nicholas Rohs, MD
Disclosures: Garon reports financial relationships with AstraZeneca, Bristol-Myers Squibb, Dracen, Dynavax, Eli Lilly, EMD Serono, Genentech, Iovance, Merck, Mirati, Neon and Novartis. Please see the abstract for all other researchers’ relevant financial disclosures.
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Edward B. Garon, MD
Edward B. Garon

The investigational MET inhibitor capmatinib appeared effective for treatment of certain patients with metastatic non-small cell lung cancer, including those with brain metastases, according to cohort analyses of the phase 2 GEOMETRY mono-1 study presented at the virtual American Association for Cancer Research Annual Meeting.

Capmatinib (INC280; Novartis, Incyte) induced deep and durable responses among patients with MET exon 14-mutated advanced NSCLC, results showed. It also had a manageable safety profile.

The multicohort, multicenter GEOMETRY mono-1 trial is investigating the efficacy and safety of capmatinib among adults in with ALK-negative and EGFR wild-type, MET exon 14-mutated or MET-amplified stage IIIB or stage IV NSCLC, including patients with neurologically stable or asymptomatic brain metastases.

“The GEOMETRY mono-1 study was designed to thoroughly evaluate the role of capmatinib in patients with abnormalities involving the MET gene,” Edward B. Garon, MD, associate professor of medicine in the division of hematology/oncology at David Geffen School of Medicine at University of California, Los Angeles, said during a presentation.

Cohort 4 of the study included patients who had two or three previous lines of therapy, whereas cohort 5b included treatment-naive patients. Patients in both cohorts received capmatinib dosed at 400 mg twice daily.

Overall response rate as determined by a blinded independent review committee using RECIST version 1.1 served as the study’s primary endpoint. Key secondary endpoints included duration of response, PFS and safety.

Ninety-seven patients, including 69 in cohort 4 (58.3% women) and 28 in cohort 5b (64.3% women), were eligible for evaluation as of April 15. Median age of patients in both cohorts was 71 years.

Patients who had no previous treatment for their disease appeared to have a greater response to capmatinib than those who had previous lines of therapy. Results showed an ORR of 40.6% (95% CI, 28.9-53.1) for cohort 4 and 67.9% (95% CI, 47.6-84.1) for cohort 5b, with median duration of response of 9.72 months (95% CI, 5.55-12.98) vs. 11.14 months (95% CI, 5.55 to not estimable).

Median PFS was 5.42 months (95% CI, 4.17-6.97) in cohort 4 and 9.69 months (95% CI, 5.52-13.86) in cohort 5b.

Thirteen patients in both cohorts had evaluable baseline brain metastases as determined by the blinded independent review committee, with a median 3.3 (range, 1-8) brain lesions per patient.

Neurological assessments based on modified RECIST version 1.1 showed seven of these patients (54%) had an intracranial response to therapy, with four showing complete response for all brain lesions. All but one patient had evidence of intracranial disease control.

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The most common treatment-related adverse events across all cohorts in the GEOMETRY mono-1 trial (n = 334) included peripheral edema (41.6%), nausea (33.2%), increased blood creatinine level (19.5%) and vomiting (18.9%). About one-third of adverse events (35.6%) were grade 3 or grade 4, and 21.9% of patients required a dose adjustment due to treatment-related adverse events. No treatment-related deaths occurred.

“In the group of patients with MET exon 14 skipping mutations — a group with typically poor outcomes using standard therapies — clinically meaningful activity has been shown [with] capmatinib,” Garon said. “As might be anticipated by the agent’s potency against MET, results were rapid and deep, leading to an impressive duration of response in both treatment-naive and previously treated patients.”

Garon acknowledged the small size of the treatment-naive cohort in the trial. Nevertheless, the “particularly important results” underline the need for early molecular evaluation of tumors, he said.

Garon concluded by highlighting the significance of the results among patients with brain metastases.

“The preclinical suggestion that efficacy in the central nervous system should be seen clinically is now demonstrated among patients in the GEOMETRY mono-1 trial, and it will be exciting to see further validation of this data,” he said. – by Drew Amorosi

Reference:

Garon EB, et al. Abstract CT082. Presented at: AACR Annual Meeting; April 27-28, 2020 (virtual meeting).

Disclosures: Garon reports financial relationships with AstraZeneca, Bristol-Myers Squibb, Dracen, Dynavax, Eli Lilly, EMD Serono, Genentech, Iovance, Merck, Mirati, Neon and Novartis. Please see the abstract for all other researchers’ relevant financial disclosures.