PERSPECTIVE: mCRC With Acquired Resistance to Anti-EGFR Therapy Due to MET Amplification
A phase 2 clinical study of tepotinib combined with cetuximab in patients with left-sided metastatic colorectcal cancer (mCRC) in RAS/BRAF wild type and with acquired resistance to anti-EGFR targeted antibody treatment due to MET amplification
ClinicalTrials.gov:
ACTIVE, NOT RECRUITING
Purpose of this study
In this phase 2, single-arm trial the safety and efficacy of tepotinib, an oral once-daily MET inhibitor, will be investigated in combination with cetuximab in patients with RAS/BRAF wild-type, left-sided mCRC and acquired resistance to prior anti-EGFR monoclonal antibody therapy due to MET amplification
The primary outcomes of the trial are:
- Dose-limiting toxicities (first cycle only)
- Objective response (by investigator)
The trial will also measure:
- Duration of response, progression-free survival, overall survival (by investigator)
- Safety
- Immunogenicity by anti-drug antibodies
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Key inclusion criteria for PERSPECTIVE*
- Locally advanced or metastatic left-sided CRC with documented RAS/BRAF wild-type gene
- MET amplification in plasma and/or tissue biopsy collected after progression on previous anti-EGFR therapy (assessed via an assay with appropriate regulatory status)
- Prior anti-EGFR antibody therapy and acquired resistance to the most recent anti-EGFR monoclonal antibody therapy†
- ECOG performance status 0 or 1
- Age ≥18 years
Key exclusion criteria for PERSPECTIVE*
- Patients with symptomatic CNS metastases who are neurologically unstable, or who have brain metastases as the only measurable lesion
- Prior anticancer therapy, other than anti-EGFR-containing regimen including associated chemotherapy, within 21 days prior to the first dose of study treatment
- Discontinuation of most recent cetuximab- or panitumumab-containing therapy due to adverse event
- Prior treatment with agents targeting HGF/MET pathway
PERSPECTIVE Study Design
*For a full list of all outcome measures and inclusion and exclusion criteria, please visit ClinicalTrials.gov NCT04515394.
†Patients must have had a radiologically confirmed response (for at least 4 months) or stable disease (for a least 6 months) to treatment with previous anti-EGFR antibody therapy, followed by radiologically documented disease progression. Radiological assessments must be made according to RECIST v1.1.
‡Target enrollment.
§Patients will receive an initial dose of tepotinib, 500 mg QD (450 mg active moiety), combined with an initial dose of cetuximab 400 mg/m² (unless cetuximab was given as prior line therapy), followed by a continuous dose of tepotinib (500 mg QD) combined with cetuximab 250 mg/m² once weekly. If 500 mg QD of tepotinib is not tolerated, the continuous dose should be reduced to 250 mg QD with 250 mg/m² of cetuximab once weekly.
¶Treatment continues until progression of disease, death, withdrawal of consent, or development of unacceptable toxicities.
#Patients who have not received prior cetuximab as prior line of therapy or received the last dose longer than 3 weeks ago will receive an initial dose of cetuximab 400 mg/m². Cetuximab is not approved for use in combination with tepotinib in any indication.
DC, disease control; DLT, dose-limiting toxicity; DOR, duration of response; OR, objective response; OS, overall survival; PFS, progression-free survival; QD, once daily; RP2D, recommended phase 2 dose.
Reference:
- ClinicalTrials.gov. Study of Tepotinib Combined With Cetuximab in Participants With Left-Sided RAS/BRAF Wild Type Metastatic Colorectal Cancer (PERSPECTIVE). https://clinicaltrials.gov/ct2/show/NCT04515394. Accessed July 2, 2021.
- Bekaii-Saab T., van Cutsem E., Cubillo A., Rodriguez Salas N., Raghav K., López C., et al. PERSPECTIVE: Tepotinib + cetuximab in patients with RAS/BRAF wild-type left-sided metastatic colorectal cancer (mCRC) and acquired resistance to anti-EGFR antibody therapy due to MET amplification. Presented at ASCO Virtual Congress 2021: June 4–8, 2021 [Poster TPS3616]
Tepotinib is being investigated in this clinical trial and is under clinical investigation in several countries. This page describes one of the clinical trials for tepotinib, and it includes information about how the safety and efficacy of tepotinib will be measured and evaluated. The safety and efficacy of tepotinib have to be investigated following the respective local regulations and laws. There is no guarantee that tepotinib will be approved in the sought-after indication by the competent health authority in your country.
PERSPECTIVE Clinical Trial Locations
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Tepotinib is currently approved for treating advanced or metastatic METex14 NSCLC in many countries globally, including the United States and the European Union, and is under clinical investigation in various other countries. The safety and efficacy of tepotinib must be investigated following the respective national regulations and laws. There is no guarantee that tepotinib will be approved in the sought-after indication by the health authority in your country.
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