Clinical trial · Interventional
Study of Safety and Efficacy of INC280 and Cetuximab, in Adult c-MET Positive mCRC and HNSCC Patients After Progression on Cetuximab or Panitumumab Therapy
A Phase Ib, Open-label, Multicenter, Dose Escalation and Expansion Study, to Evaluate the Safety, Pharmacokinetics and Activity of INC280 in Combination With Cetuximab in c-MET Positive CRC and HNSCC Patients Who Have Progressed After Anti-EGFR Monoclonal Antibody Therapy.
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This was an open-label, phase Ib, multicenter clinical trial to determine the MTD/RDE of the orally administered c-MET inhibitor INC280 in combination with cetuximab. This combination was to be explored in c-MET positive mCRC and HNSCC patients whose disease progressed on cetuximab or panitumumab treatment. The dose escalation part was to be guided by a Bayesian Logistic Regression Model with overdose control. At MTD/RDE, additional mCRC and HNSCC patients who progressed on cetuximab or panitumumab treatment were to be enrolled in two expansion groups to further assess the anti-tumor activity and the safety and tolerability of the combination of INC280 and cetuximab. Patients were to receive INC280 on a continuous bid dosing regimen and cetuximab every week. A treatment cycle was defined as 28 days with no scheduled break between cycles. The trial was terminated because of difficulties in identifying patients who met the eligibility criteria.
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Metastatic Colorectal Cancer | Malignant Colorectal Neoplasm | CURATED_BROADER | 0.80 |
| Squamous Cell Carcinoma of Head and Neck (SCCHN) | Head and Neck Squamous Cell Carcinoma | ALIAS | 0.85 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| cetuximab | Drug | Cetuximab | ALIAS |
| INC280 | Drug | Capmatinib | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- c-MET positive mCRC and HNSCC
- description
- c-MET positive and K/NRAS WT mCRC and c-MET positive HNSCC patients
- interventionNames
- Drug: INC280
- Drug: cetuximab
Primary outcomes (1)
- measure
- Incidence of Dose Limiting Toxicities (DLTs)
- timeFrame
- during Cycle 1 and up to 4 weeks from the time of study treatment start
- description
- To estimate the MTD and/or RDE of INC280 in combination with cetuximab in c-MET positive mCRC and HNSCC patients as measured by the incidence of DLTs in Cycle 1. A treatment cycle was defined as 28 days with no scheduled break between cycles.
Secondary outcomes (7)
- measure
- Frequency of Adverse Events (AEs)/Serious Adverse Events (SAEs)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Male or female aged ≥ 18 years * Metastatic colorectal cancer or head and neck squamous cell carcinoma * c-MET positive (defined by c-MET IHC intensity score +2 in ≥ 50% of tumor cells and MET gene copy number ≥ 5 by FISH or IHC intensity score +3 in ≥ 50% of tumor cells) and K/NRAS WT status for mCRC patients only * At least one previous line of treatment for the metastatic disease and the last treatment must have included cetuximab or panitumumab. Documentation of clinical benefit and subsequent progression on cetuximab or panitumumab as the most recent line of treatment is required for patients in the expansion part * Measurable disease as per RECIST v1.1 * ECOG performance status ≤ 2 Exclusion Criteria: * Prior treatment with c-MET/HGF inhibitors * History of severe reactions to cetuximab and/or panitumumab (except for G3 rash and G3 hypomagnesaemia) * History of acute or chronic pancreatitis * Active bleeding within 4 weeks prior to screening visit * Symptomatic brain metastases * Feeding tube dependence * Not adequate hematologic, renal and hepatic function
References
Publications (1)
- DERIVEDDelord JP, Argiles G, Fayette J, Wirth L, Kasper S, Siena S, Mesia R, Berardi R, Cervantes A, Dekervel J, Zhao S, Sun Y, Hao HX, Tiedt R, Vicente S, Myers A, Siu LL. A phase 1b study of the MET inhibitor capmatinib combined with cetuximab in patients with MET-positive colorectal cancer who had progressed following anti-EGFR monoclonal antibody treatment. Invest New Drugs. 2020 Dec;38(6):1774-1783. doi: 10.1007/s10637-020-00928-z. Epub 2020 May 14. PMID 32410080