A Phase I Dose Escalation Study of CGM097 in Adult Patients With Selected Advanced Solid Tumors (CCGM097X2101)

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).

Study Overview

• Status: Completed
• Conditions: Solid Tumor With p53 Wild Type Status
• Intervention / Treatment: Drug: CGM097

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Lyon Cedex, France, 69373
    • Novartis Investigative Site
• Germany
  • Essen, Germany, 45147
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 169610
    • Novartis Investigative Site
• Switzerland
  • Zuerich, Switzerland, 8091
    • Novartis Investigative Site
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute SC (2)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CGM097 - Dose escalation	Drug: CGM097; Patients treated with CGM097
EXPERIMENTAL: CGM097 - Dose Expansion at MTD or RP2D	Drug: CGM097; Patients treated with CGM097

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose Limiting Toxicities	To characterize the maximum tolerated dose (MTD) and/or identify the recommended dose for expansion(RDE) of CGM097. Dose Limiting Toxicities will be listed and their incidence summarized by primary system organ class, worst grade based on CTCAE version 4.03 and type of Adverse Event	From day 1 to day 28 of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic profile of CGM097	Plasma concentration of CGM097	At Cycle 1 Day 1, 2, 5, 8, 15 and 22, then each first day of the Cycle (28 days per Cycle) until discontinuation.
Tumor response per RECIST	This includes duration of response and progression free survival	Baseline, then every third cycle (approximately every 12 weeks), until disease progression or discontinuation.
Pharmacodynamic effect of CGM097	Changes of tumors markers in tumor tissue and blood	At baseline, Cycle 2 Day 8 and at disease progression.
Changes in laboratory values, vital signs or cardiac functionality, dose reduction, dose interruption and dose intensity, incidence and severity of adverse events.	Changes in laboratory values, vital signs or cardiac functionality, dose reduction, dose interruption and dose intensity, incidence and severity of adverse events.	At Cycle 1 Day 1, 2, 5, 8, 15, 22 and 28, Cycle 2 Day 1, 8,15 and 22, then each Day 1 and 15 of the Cycle until discontinuation. For dose interruption, dose intensity and adverse events: each day of the Cycle until discontinuation (28 days per Cycle).

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Bauer S, Demetri GD, Halilovic E, Dummer R, Meille C, Tan DSW, Guerreiro N, Jullion A, Ferretti S, Jeay S, Van Bree L, Hourcade-Potelleret F, Wuerthner JU, Fabre C, Cassier PA. Pharmacokinetic-pharmacodynamic guided optimisation of dose and schedule of CGM097, an HDM2 inhibitor, in preclinical and clinical studies. Br J Cancer. 2021 Aug;125(5):687-698. doi: 10.1038/s41416-021-01444-4. Epub 2021 Jun 17.

Helpful Links

• Study Results

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 20, 2013
• Primary Completion (ACTUAL): July 24, 2020
• Study Completion (ACTUAL): July 24, 2020

Study Registration Dates

• First Submitted: January 2, 2013
• First Submitted That Met QC Criteria: January 2, 2013
• First Posted (ESTIMATE): January 4, 2013

Study Record Updates

• Last Update Posted (ACTUAL): June 15, 2021
• Last Update Submitted That Met QC Criteria: June 10, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: p53, solid tumor
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CCGM097X2101; 2012-000940-87 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No