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

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ClinicalTrials.gov Identifier: NCT03799731
Recruitment Status : Active, not recruiting
First Posted : January 10, 2019
Last Update Posted : July 31, 2019
Sponsor:
Information provided by (Responsible Party):
GamaMabs Pharma

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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: GM102 antibody Drug: Trifluridine/Tipiracil Phase 2

Detailed Description:

GM102 is a humanized low fucose monoclonal antibody with a high affinity to AMHRII receptor (fetal receptor mediating the activity of AMH, reexpressed in a variety of solid tumors). GM102 acts through engagement of immune cells (macrophages, natural killer (NK) cells) to trigger ADCC (antibody dependent cellular cytotoxicity) and phagocytosis of tumor cells.

AMRHII expression was found in 73% of primary colorectal tumors tested.

Advanced/metastatic colorectal cancer (CRC) remains an unmet need disease, with few therapeutic options beyond two or three lines of therapy.

CRC is characterized by a tumor microenvironment (TME) particularly rich in macrophages and more specifically macrophages capable of tumor phagocytosis. The pattern of the TME remains a major prognostic factor in the metastatic setting.

C201 consists of two parallel cohorts for patients with advanced or metastatic colorectal cancer in two different settings of the disease:

  • Cohort I (GM102 single agent) in refractory patients, having exhausted all therapeutic options. Patients will receive GM102 alone at the dose of 7 mg/kg administered by intravenous infusion at Day 1, Day 8, Day 15 and Day 22 of each 28-day cycle
  • Cohort II (GM102 in combination with trifluridine/tipiracil) in patients candidate to receive single agent trifluridine/tipiracil, after at least two lines of treatment for the advanced or metastatic disease. Patients will receive GM102 at the dose of 7 mg/kg administered by intravenous infusion at Day 1, Day 8, Day 15 and Day 22 and trifluridine/tipiracil at 35 mg/m² per dose twice daily orally administered on Days 1 to 5 and Days 8 to 12 of each 28-day cycle.

Patients will be treated with GM102 (Cohort I) or GM102 and trifluridine/tipiracil (Cohort II) until confirmed progression or toxicity.

A Trial Steering Committee (TSC) will analyze and qualify GM102 activity and toxicities and will provide recommendations on the Investigational Medicinal Product (IMP) continuation.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 39 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open, Non Controlled, Parallel Cohorts, Multicenter, Phase 2A Study for Evaluation of the Antitumor Activity of GM102 Single Agent and in Combination With Chemotherapy in Patients With Locally Advanced Or Metastatic Colorectal Cancer
Actual Study Start Date : July 11, 2018
Estimated Primary Completion Date : December 1, 2019
Estimated Study Completion Date : December 1, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort I: GM102 single agent
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 antibody
GM102 7 mg/kg weekly
Other Name: GM102

Experimental: Cohort II: GM102 + trifluridine/tipiracil
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 antibody
GM102 7 mg/kg weekly
Other Name: GM102

Drug: Trifluridine/Tipiracil
Lonsurf 35 mg/m² twice daily during 10 days per cycle
Other Name: Lonsurf




Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: Through study completion, an average 1 year ]
    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


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: Through study completion, an average 1 year ]
    ORR using immune Response Evaluation Criteria In Solid Tumors (iRECIST)

  2. Clinical benefit rate (CBR) [ Time Frame: up to 4 months ]
    CBR at 8 and 16 weeks defined as the number of non-progressors using RECIST 1.1 and iRECIST criteria

  3. Tumor Growth Rate (TGR) before and under treatment [ Time Frame: up to 2 months ]
  4. Progression Free Survival (PFS) [ Time Frame: Through study completion, an average 1 year ]
  5. Overall Survival (OS) [ Time Frame: Through study completion, an average 1 year ]
  6. Incidence of Serious Adverse Event (SAE) and Treatment Emergent Adverse Event (TEAE) [ Time Frame: Through study completion, an average 1 year ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03799731


Locations
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Belgium
Cliniques Universitaires Saint-Luc
Brussels, Belgium
UZ Gasthuisberg
Gent, Belgium
UZ Leuven
Leuven, Belgium
Czechia
University Hopistal Olomouc
Olomouc, Czechia
University Hospital Motol
Praha, Czechia
Sponsors and Collaborators
GamaMabs Pharma
Investigators
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Principal Investigator: Eric Van Cutsem, MD UZ Leuven

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Responsible Party: GamaMabs Pharma
ClinicalTrials.gov Identifier: NCT03799731     History of Changes
Other Study ID Numbers: C201
First Posted: January 10, 2019    Key Record Dates
Last Update Posted: July 31, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Trifluridine
Antibodies
Immunologic Factors
Physiological Effects of Drugs
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents