A Phase I Dose Escalation Study of CGM097 in Adult Patients With Selected Advanced Solid Tumors

A Phase I, Open-label, Multi-center, Dose Escalation Study of Oral CGM097, a p53/HDM2-interaction Inhibitor, in Adult Patients With Selected Advanced Solid Tumors

This is a first in human phase I study of single agent CGM097 in patients with advanced solid tumors who have progressed despite standard therapy or for whom no standard therapy exists. The tumor must be characterized by p53wt status. The study consists of a dose escalation part where patients will receive escalating doses of CGM097, and a dose expansion part in which patients are given CGM097 at the maximum tolerated dose (MTD) or Recommended Phase 2 Dose (RP2D). Each dose escalation step will be decided based on the recommendation from an adaptive Bayesian logistic regression model (BLRM).

This is a multi-center, open-label, dose finding, phase I study of single agent CGM097, administered in patients with advanced solid tumors who have progressed despite standard therapy or for whom no standard therapy exists. Patients' tumors must be characterized by p53wt status.

The study consists of a dose escalation part, where cohorts of three to six newly enrolled patients will receive escalating doses of CGM097, and a dose expansion part, in which patients are given CGM097 the maximum tolerated dose (MTD) or Recommended Phase 2 Dose (RP2D). Novartis and the site investigators will jointly decide on each dose escalation step based on the recommendation from an adaptive Bayesian logistic regression model (BLRM). If safety data should indicate a lower increment than suggested by the BLRM, the next dose level (DL) will be adjusted accordingly.

Inclusion Criteria:

• Patient has advanced solid malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists
• Tumor of the patient is p53wt
• Evaluable disease as determined by RECIST 1.1
• WHO performance status 0-2

Exclusion criteria:

• Prior treatment with CGM097 or other p53/HDM2-interaction inhibitor
• Patient with symptomatic or growing CNS metastatic lesions
• Concurrent other malignancy
• Clinically significant cardiac disease as defined in the protocol
• Diagnosis of acute or chronic pancreatitis
• Concomitant therapy that precludes enrollment, as defined in the protocol
• Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 2 weeks after study drug discontinuation
• Pregnant or nursing women

Other protocol-defined inclusion/exclusion criteria may apply.