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

Novartis

Status and phase: Terminated; Phase 1

Conditions: Metastatic Colorectal Cancer; Squamous Cell Carcinoma of Head and Neck (SCCHN)

Treatments: Drug: INC280; Drug: cetuximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02205398

2014-000579-20 (EudraCT Number)

CINC280X2104

Details and patient eligibility

About

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.

Enrollment: 13 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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13 participants in 1 patient group

c-MET positive mCRC and HNSCC

Experimental group

Description:

c-MET positive and K/NRAS WT mCRC and c-MET positive HNSCC patients

Treatment:

Drug: cetuximab

Drug: INC280