Jüergen Wolf, MD, medical director of the Center for Integrated Oncology and professor of Interdisciplinary Translational Oncology at the University Hospital of Cologne, discusses the design and rationale of the phase 2 GEOMETRY mono-1 study with capmatinib (Tabrecta) in 

amplified, advanced non–small cell lung cancer (NSCLC).

The GEOMETRY mono-1 study was a global, multicohort trial evaluating capmatinib in patients with METex14-mutated advanced NSCLC who received prior immunotherapy. The trial systematically evaluated patients according to the line of therapy and molecular driver status, says Wolf. Within the 4 different cohorts, 3 had low and medium amplification with up to a copy number of 9, while the fourth cohort included highly amplified patients, with a copy number of ≥10.

Last year, the initial results were reported on patients with METex14 skipping mutations. Results showed that there was efficacy with the agentin pretreated patients with advanced NSCLC who were receiving treatment in the second- or third-line of therapy, says Wolf. Patients experienced an overall response rate of 39.1% and duration of response was 9.72 months. For this cohort, the primary end point was met because a lower boundary of 35% was assumed. Investigators determined that the trial would be successful if in the pretreatment setting, at least 35% of the patients showed a response. These datacompare favorably with that seen with standard relapsed therapies, concludes Wolf.

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Jüergen Wolf, MD, discusses the design and rationale of the phase 2 GEOMETRY mono-1 study with capmatinib (Tabrecta) in METex14-mutated or high MET amplified, advanced non–small cell lung cancer.

Dr. Wolf on the Design of GEOMETRY mono-1 Trial in METex14-Mutated NSCLC

Jüergen Wolf, MD, medical director of the Center for Integrated Oncology and professor of Interdisciplinary Translational Oncology at University Hospital of Cologne, discusses data the phase 2 GEOMETRY mono-1 trial with capmatinib (Tabrecta) in patients with 

amplified advanced non—small cell lung cancer (NSCLC).

At the 2020 ASCO Virtual Scientific Program, data from 2 cohorts of the trial, says Wolf. Cohort 6 was a confirmatory cohort. Investigators saw the preplanned statistical hypothesis which involved treating more patients with either high-level 

ex14 mutation whose disease progressed on 1 prior line of systemic therapy.

ex14-skipping mutation, the overall response rate with capmatinib was 48.4%; this confirms what had been reported last year. The same held true with progression-free survival, which was around 8.11 months in that cohort. While these are confirmatory results, they show true efficacy reported with the agent. Promising data have already led to the FDA approval of the drug in this patient population, concludes Wolf.

Jüergen Wolf, MD, discusses data the phase 2 GEOMETRY mono-1 trial with capmatinib (Tabrecta) in patients with METex14-mutated or high MET amplified advanced non–small cell lung cancer.

Dr. Wolf on Updated Findings With Capmatinib in METex14-Mutant NSCLC

Jüergen Wolf, MD, medical director, Center for Integrated Oncology, professor, Interdisciplinary Translational Oncology at University Hospital of Cologne, discusses the primary efficacy data of the phase II GEOMETRY mono-1 trial exploring the MET inhibitor capmatinib as treatment for patients with non-small cell lung cancer (NSCLC) and exon-14 mutations.

Patients with an exon-14 mutations account for about 4% of all patients with NSCLC. In the GEOMETRY mono-1 trial, investigators are evaluating the use of capmatinib in patients with different 

 alterations, such as MET exon-14 skipping and MET amplifications.

At the 2019 ASCO Annual Meeting, Wolf presented the primary efficacy data with the agent in patients with exon-14—mutated disease. In the trial, two cohorts&mdash;treatment-naïve patients and pretreated patients&mdash;were tested separately.

Capmatinib yielded promising overall response rates (ORR) over the standard treatment of platinum-based chemotherapy in the treatment-naïve cohort. Specifically, the ORR was 70% with capmatinib versus 20% with chemotherapy. The duration of response observed with the MET inhibitor was about 11 months. Furthermore, the cohort of pretreated patients had an ORR of 40%, with a duration of response of 10 months, says Wolf.

The toxicity seen with capmatinib was significantly lower than what was seen with traditional chemotherapy. The most common adverse events associated with the agent were peripheral edema and gastrointestinal toxicities; however, these events are typically manageable in the clinical setting, says Wolf. Based on what has been seen with this trial, capmatinib as may be a favorable treatment option over standard chemotherapy in this patient population.

Jüergen Wolf, MD, medical director, Center for Integrated Oncology, professor, Interdisciplinary Translational Oncology at University Hospital of Cologne, discusses the primary efficacy data of the phase II GEOMETRY mono-1 trial exploring the MET inhibitor capmatinib as treatment for patients with non-small cell lung cancer and exon-14 mutations.

Dr. Wolf on GEOMETRY mono-1 Phase II Trial With Capmatinib in NSCLC

Juergen Wolf, MD, medical director, Center for Integrated Oncology, University Hospital of Cologne, Köln Bonn, Köln, Germany, discusses the GEOMETRY study in patients with 

-positive non—small cell lung cancer (NSCLC).

The GEOMETRY study is evaluating the MET inhibitor capmatinib (INC280) in patients with 

 amplified advanced NSCLC. Phase II results were presented at the 2018 ESMO Congress. The primary endpoint of the phase II trial was overall response rate (ORR) by blinded independent central review (BIRC) per RECIST v1.1. The secondary endpoint was duration of response by BIRC.

In patients who had received 1 to 2 prior lines of therapy, capmatinib showed clinically meaningful response rates, as well as a manageable toxicity profile. The response to capmatinib was greater in patients with treatment-naive disease with 

exon 14 mutations. The ORR by BIRC in this population was 72%.

Juergen Wolf, MD, medical director, Center for Integrated Oncology, University Hospital of Cologne, Köln Bonn, Köln, Germany, discusses the GEOMETRY study in patients with MET-positive non–small cell lung cancer (NSCLC).
 

Juergen Wolf, MD

Articles

Dr. Wolf on the Design of GEOMETRY mono-1 Trial in METex14-Mutated NSCLC

Dr. Wolf on Updated Findings With Capmatinib in METex14-Mutant NSCLC

Dr. Wolf on GEOMETRY mono-1 Phase II Trial With Capmatinib in NSCLC

Dr. Wolf Discusses the GEOMETRY Study in MET+ NSCLC