Study for Evaluation of Murlentamab (GM102) Anti-tumoral Activity in Colorectal Cancers

NCT03799731 | Completed Phase 2

• 1 other identifier: C201
• Study Type: interventional
• Target: 65
• Locations: 2 countries
• Sites: 5

Brief Summary

Phase 2A study, assessing the antitumor activity and the safety profile of GM102, a new compound (monoclonal antibody), administered alone or in combination with chemotherapy in patients with locally advanced or metastatic colorectal cancer. The primary objective of the study is to evaluate the antitumor activity of GM102 single agent and in combination with trifluridine/tipiracil.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate (ORR)

  ORR from the end of cycle 2 and subsequently confirmed at least 4 weeks later using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1

  Through study completion, an average 1 year

• Progression Free Survival (PFS) at 6 months

  Proportion of patients without documented progression at 6 months

  6 months after the first infusion

Secondary Outcomes (11)

• Immune Overall Response Rate (iORR)

  Through study completion, an average 1 year

• Clinical Benefit Rate (CBR)

  up to 4 months

• Tumor Growth Rate (TGR) before and under treatment

  up to 2 months

• Progression Free Survival (PFS)

  Through study completion, an average 1 year

• Overall Survival (OS)

  Through study completion, an average 1 year

Study Arms (3)

Cohort I: GM102 single agent

EXPERIMENTAL

GM102 will be intravenously administered at the dose of 7 mg/kg on Days 1, 8, 15 and 22 of each 28-day cycle

Drug: GM102

Cohort II: GM102 + trifluridine/tipiracil

EXPERIMENTAL

GM102 will be intravenously administered at the dose of 7 mg/kg on Days 1, 8, 15 and 22, and trifluridine/tipiracil will be orally administered at the dose of 35 mg/m² twice daily on Days 1 to 5 and days 8 to 12 of each 28-day cycle

Drug: GM102; Drug: Trifluridine/Tipiracil

Cohort II expansion: GM102 + trifluridine/tipiracil

EXPERIMENTAL

GM102 will be intravenously administered at the dose of 7 mg/kg on Days 1, 8, 15 and 22, after a loading dose of 10 mg/kg q1w during 28-day cycle 1, and trifluridine/tipiracil will be orally administered at the dose of 35 mg/m² twice daily on Days 1 to 5 and days 8 to 12 of each 28-day cycle

Drug: Trifluridine/Tipiracil; Drug: GM102 expansion

Interventions

GM102 DRUG

GM102 7 mg/kg weekly

Cohort I: GM102 single agent; Cohort II: GM102 + trifluridine/tipiracil

Trifluridine/Tipiracil DRUG

Lonsurf 35 mg/m² twice daily during 10 days per cycle

Also known as: Lonsurf

Cohort II expansion: GM102 + trifluridine/tipiracil; Cohort II: GM102 + trifluridine/tipiracil

GM102 expansion DRUG

GM102 7 mg/kg weekly after a loading dose of 10 mg/kg q1w during 28-day cycle 1

Cohort II expansion: GM102 + trifluridine/tipiracil

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed metastatic or locally advanced colorectal adenocarcinoma.
• Having failed the previous line of treatment for locally advanced or metastatic disease and having received at least two systemic chemotherapy regimens for metastatic colorectal cancer; adjuvant regimen can be considered as one chemotherapy regimen for metastatic disease if the participant had disease recurrence within 6 months of completion.
• At least one of the tumor sites amenable to core needle biopsy (may not be the site of disease for measuring antitumor response). Patient must agree to this pre-treatment biopsy and on the principle of a second biopsy under treatment; however, if eventually the second biopsy cannot be performed, patients will continue on the study and will be considered evaluable for efficacy.
• Available archived CRC tumor tissue sample
• At least one measurable lesion (superior or equal to 1.0 cm longest diameter or superior or equal to 1.5 cm in short axis for malignant lymph nodes) based on RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 on the screening CT-scan.
• Written Informed Consent forms signed.
• Willing and able to comply with the trial requirements.
• Covered by healthcare insurance in accordance with local requirements.
• For cohort I (single agent GM102) only: refractory patients, having exhausted all therapeutic options.
• For cohort II (GM102 in combination with trifluridine/tipiracil) only: patients eligible for trifluridine/tipiracil who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-Vascular Endothelial Growth Factor (anti-VEGF) agents, regorafenib and anti-Epithelial Growth Factor Receptor (anti-EGFR) agents. Patients must have received at least 2 prior lines of standard chemotherapy for metastatic CRC.

You may not qualify if:

• Age \< 18 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status superior or equal to 2.
• Life expectancy \< 12 weeks.
• Major surgery or radiotherapy within 21 days prior to Cycle 1 Day 1 or anticipation of needing such procedure while receiving study treatment.
• Known or symptomatic brain metastasis (other than totally resected or previously irradiated and non-progressive/relapsing) or lepto-meningeal carcinomatosis.
• Concurrent treatment with any other anticancer therapy (or investigational agent) or received any anticancer therapy (or investigational agent) within 4 weeks prior to first treatment.
• Known severe anaphylactic or other hypersensitivity reactions to Investigational Medicinal Product (IMP) and/or its excipients.
• Unresolved toxicity superior or equal to Grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation, and platinum induced neurotoxicity).
• Serious concomitant illness, e.g. active infection requiring systemic antibiotic, antifungal or antiviral drug, or physical examination or laboratory abnormalities, that, in the opinion of the Investigator, would compromise protocol objectives.
• Poor bone marrow reserve as defined by white blood cell \< 3.0 x 10E9/L, neutrophils \< 1.5 x 10E9/L or haemoglobin \< 9.0 g/dL or platelet count \< 100 x 10E9/L.
• Poor organ function as defined by any one of the following: serum creatinine \> 1.5 x upper limit of normal (ULN), total bilirubin \> 1.5 x ULN or \> 2.5 x ULN if due to Gilbert's syndrome, AST and ALT \> 2.5 x ULN in the absence of liver metastasis or \> 5 x ULN in case of documented liver metastasis.
• Severe New York Heart Association (NYHA) III and IV heart failure.
• Pregnancy or breastfeeding.
• Patient with reproductive potential who does not agree to use an accepted highly effective method of contraception - per investigator's judgment - during the study period and for at least 6 months following completion of study treatment.
• Patient deprived of liberty by a judicial or administrative decision, patient admitted to a social institution or who is under a measure of legal protection, patient hospitalized without consent or who is in an emergency situation.

Sponsors & Collaborators

• GamaMabs Pharma: lead

Study Sites (5)

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

UZ Gasthuisberg

Ghent, Belgium

Location

UZ Leuven

Leuven, Belgium

Location

University Hopistal Olomouc

Olomouc, Czechia

Location

University Hospital Motol

Prague, Czechia

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

trifluridine tipiracil drug combination

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Eric Van Cutsem, MD

  UZ Leuven, Belgium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2019
• First Posted: January 10, 2019
• Study Start: July 11, 2018
• Primary Completion: January 19, 2021
• Study Completion: February 10, 2021
• Last Updated: April 14, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (2); BE (3)