First-in-Man, Dose-escalation Trial of c-Met Kinase Inhibitor EMD 1204831 in Subjects With Advanced Solid Tumors

A Phase I Open-label, Non-randomized, Dose-escalation First-in-man Trial to Investigate the c-Met Kinase Inhibitor EMD 1204831 in Subjects With Advanced Solid Tumors

EMD Serono has closed enrollment into this trial prior to determination of maximum tolerated dose (MTD). EMD Serono has decided not to pursue the development of EMD 1204831 in patients with advanced solid tumors for reasons other than safety.

This is a an open-label, dose-escalation, first-in-man (FIM) study designed to explore the safety, tolerability, pharmacokinetics, and clinical activity of an investigational drug, EMD 1204831, in patients with advanced solid tumors who have not responded to previous therapies or for whom no other therapies are available. Subjects will receive EMD 1204831 twice a day (BID) during each 21-day cycle until disease progression or unacceptable toxicity.

Inclusion Criteria:

Main Inclusion Criteria

1. Histologically or cytologically confirmed solid tumor, either refractory standard therapy or for which no effective standard therapy is available
2. Measurable or evaluable disease, as defined by RECIST 1.0
3. Men or women aged ≥ 18 years
4. ECOG performance status of 0 to 2
5. Adequate hematological function: Hemoglobin ≥ 9.0 g/dL; Neutrophils > 1.5 x 109/L; Platelets ≥ 100 x 109/L
6. Adequate liver function: Total bilirubin ≤ 1.5 x ULN; AST/ ALT ≤ 2.5 x ULN
7. For subjects with liver metastases: Total bilirubin ≤ 1.5 x ULN; AST/ALT ≤ 5 ULN
8. Adequate renal function: Serum creatinine < 1.5 x ULN, and/or Calculated creatinine clearance > 60 mL/min
9. Resolution of all acute chemotherapy, radiotherapy or surgery-related AEs to Grade ≤1, except for alopecia
10. Recovery from any surgical intervention
11. Subjects enrolling after the MTD has been determined must present specific c-Met alterations (overexpression, amplification, mutation)

Exclusion Criteria:

Main Exclusion Criteria

1. Received chemotherapy, immunotherapy, hormonal therapy (except subjects with prostate cancer), biologic therapy, or any other investigational agent or anticancer therapy within 28 days (or five half-lives for non-cytotoxics, whichever is shorter), of Day 1 of trial treatment (six weeks for nitrosureas or mitomycin C)
2. Received extensive prior radiotherapy on more than 30% of bone marrow
3. Symptomatic primary tumors or metastasis of brain and/or central nervous system, uncontrolled with antiepileptics and requiring high doses of steroids
4. Medical history of liver fibrosis/ cirrhosis
5. Medical history of surgery within six weeks prior to enrollment
6. Neuropathy Grade ≥ 2
7. Requires concurrent treatment with a non-permitted drug
8. Absence or abnormal pupillary reflex