FDA Approves FoundationOne Liquid CDx as Companion Diagnostic for Capmatinib in METex14+ NSCLC

FDA

The FDA has approved the FoundationOne Liquid CDx for use as a companion diagnostic to assist in the identification of patients with metastatic non–small cell lung cancer (NSCLC) whose tumors harbor MET exon 14 skipping mutations (METex14) and who could derive benefit from treatment with capmatinib (Tabrecta).¹

In May 2020, the regulatory agency granted an accelerated approval to capmatinib for use in this patient population based on initial data from the phase 2 GEOMETRY mono-1 study (NCT02414139). The agent was found to elicit an objective response rate (ORR) of 67.9% (95% CI, 47.6%-84.1%) per independent review in treatment-naïve patients with METex14-altered NSCLC.²

“For [patients with] lung cancer [and] METex14, having the option of a non-invasive liquid biopsy expands access to this first-of-its-kind therapy and helps meet a critical patient need,” Brian Alexander, MD, MPH, chief executive officer of Foundation Medicine, stated in a press release. “This approval, coupled with last year’s simultaneous therapy and companion diagnostic approval for [capmatinib] for our tissue test, FoundationOne CDx, is an important advancement and demonstrates the value of having multiple highly-validated comprehensive genomic testing options for physicians to consider for the individual needs of each patient.”

The liquid assay assesses over 300 cancer-related genes for genomic alterations in a blood sample. The test has now been approved for use as a companion diagnostic for 9 targeted therapeutics across 4 cancer types.

The report that comes with the liquid assay provides insight into microsatellite instability blood tumor mutational burden and single-gene alterations like NTRK fusions to inform the use of other options. The test also provides information on relevant clinical trials and content associated with professional guidelines in oncology for patients with solid tumors.

The prospective, international, open-label phase 2 trial examined the safety and efficacy of capmatinib in patients with NSCLC harboring METex14 and MET amplification.³ To be eligible for enrollment, patients needed to be at least 18 years of age, have stage IIIB or IV disease with any histologic features, and at least 1 measurable lesion per RECIST v. 1.1 criteria. Patients could not have an activating EGFR mutation or an ALK fusion.

Patients were assigned to cohorts based on their mutational status and prior lines of therapy received. The study was comprised of 5 cohorts; cohorts 1 and 5 had subcohorts. Cohorts 6 and 7 were expansion cohorts that were added to provide supportive clinical evidence.

The primary end point of the trial was overall response per independent review committee (IRC) per RECIST v1.1 criteria. Key secondary end points included investigator-assessed response and duration of response (DOR), investigator-evaluated and IRC-evaluated time to response, disease control, progression-free survival (PFS), safety, and pharmacokinetics.

A total of 364 patients with advanced NSCLC were enrolled to the trial. Across cohorts 1 to 5, 97 patients had a tumor that harbored a METex14 mutation and 210 had tumors with MET amplification. Previously treated patients in cohorts 1 to 4 had previously received 1 or 2 lines of therapy; patients in cohorts 5a and 5b were treatment naïve.

Additionally, cohorts who harbored METex14 mutations were found to have a slightly higher median age vs those with MET amplifications, at 71 years and 60 to 70 years, respectively. Patients who had METex14-mutated disease had a higher likelihood of being women and to have never smoked vs those with MET amplifications.

Among patients with advanced METex14-mutated NSCLC, the IRC-assessed ORR was 41% (95% CI, 29%-53%) in previously treated patients and 68% (95% CI, 48%-84%) in those who had not received prior treatment. The median DOR per IRC evaluation was 9.7 months (95% CI, 5.6-13.0) in previously treated patients and 12.6 months (95% CI, 5.6–not estimable) in treatment-naïve patients.

Responses to the agent were rapid; 82% and 68% of previously treated and naïve patients, respectively, experienced a response at the first tumor assessment following treatment initiation.

The median IRC-assessed PFS with capmatinib was 5.4 months (95% CI, 4.2-7.0) in previously treated patients and 12.4 months (95% CI, 8.2–not estimated) in those who had not received prior treatment. Investigator-assessed PFS findings were comparable to those of the IRC.

Among patients with advanced NSCLC and MET amplification, the IRC-assessed ORR was 12% (95% CI, 4%-26%) in those who had tumor tissue with a gene copy number of 6 to 9, 9% (95% CI, 3%-20%) in those with tumor tissue and a gene copy number of 4 or 5, and 7% (95% CI, 1%-22%) in those who had tumor tissue with a gene copy number of less than 4. As such, these cohorts were closed for futility at the time of the interim analysis.

The IRC-assessed PFS in those who had tumor tissue with a gene copy number of 6 to 9, a gene copy number of 4 or 5, and less than 4, was 2.7 months (95% CI, 1.4-3.1), 2.7 months (95% CI, 1.4-4.1), and 3.6 months (95% CI, 2.2-4.2), respectively.

The agent demonstrated activity in patients who had tumor tissue with a gene copy number of at least 10, although responses were lower than the prespecified threshold for clinically relevant activity. The IRC-assessed ORR was 29% (95% CI, 19%-41%) in 69 previously treated patients and 40% (95% CI, 16%-68%) in 15 patients who had not previously received treatment.

The median DOR was 8.3 months (95% CI, 4.2-15.4) in 20 previously treated patients and 7.5 months (95% CI, 2.6-14.3) in 6 treatment-naïve patients. In these groups, the median PFS was 4.1 months (95% CI, 2.9-4.8) and 4.2 months (95% CI, 1.4-6.9), respectively.

References

1. Foundation Medicine expands indication for FoundationOne Liquid CDx to be used as companion diagnostic for TABRECTA (capmatinib). News release. Foundation Medicine, Inc. July 15, 2021. Accessed July 16, 2021. https://bwnews.pr/3hJ54rv
2. Novartis announces FDA approval of MET inhibitor Tabrecta for metastatic non-small cell lung cancer with METex14. News release. Novartis. May 6, 2020. Accessed July 16, 2021. https://bit.ly/2SIEmTc
3. Wolf J, Seto T, Han J-Y, et al. Capmatinib in MET exon 14–mutated or MET-amplified non–small cell lung cancer. N Engl J Med. 2020;383(10):944-957. doi:10.1056/NEJMoa2002787