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Colorectal CancerPhase 2NCT03799731

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

A Phase 2 study testing GM102, Trifluridine/Tipiracil and GM102 expansion in people with Colorectal Cancer, run by GamaMabs Pharma at 5 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer
What is being tested?
GM102, Trifluridine/Tipiracil and GM102 expansion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
65 participants
Where
5 sitesin 2 countries
Study dates
11 Jul 2018to 10 Feb 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • Known allergy to rodents.
  • Patients positive to Covid-19

Trial locations and contacts

5 sites in 2 countries.

5 sites in 2 countries

Belgium3 sites

  • Cliniques Universitaires Saint-Luc

    Brussels

  • UZ Gasthuisberg

    Ghent

  • UZ Leuven

    Leuven

Other trials in Belgium

Czechia2 sites

  • University Hopistal Olomouc

    Olomouc

  • University Hospital Motol

    Prague

Other trials in Czechia

About this study

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

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.

Read the 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 in two parallel cohorts and an expansion of cohort II for patients with advanced or metastatic colorectal cancer in two different settings of the disease:

  • Cohort I (GM102 as a 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.
  • Cohort II expansion (GM102 in combination with trifluridine/tipiracil) same as cohort II except a loading dose of 10 mg/kg q1w during 28-day cycle 1

Patients will be treated with GM102 (Cohort I) or GM102 and trifluridine/tipiracil (Cohort II and Cohort II expansion) 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.

Being tested
GM102, Trifluridine/Tipiracil, GM102 expansion
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GM102Drug

    GM102 7 mg/kg weekly

  • Trifluridine/TipiracilDrug

    Also called Lonsurf

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

  • GM102 expansionDrug

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

Study groups in NCT03799731
Study groupRoleWhat they receive
Cohort I: GM102 single agentExperimentalGM102 will be intravenously administered at the dose of 7 mg/kg on Days 1, 8, 15 and 22 of each 28-day cycle
Receives: Drug: GM102
Cohort II: GM102 + trifluridine/tipiracilExperimentalGM102 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
Receives: Drug: GM102; Drug: Trifluridine/Tipiracil
Cohort II expansion: GM102 + trifluridine/tipiracilExperimentalGM102 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
Receives: Drug: Trifluridine/Tipiracil; Drug: GM102 expansion

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Through study completion, an average 1 year

  2. Progression Free Survival (PFS) at 6 months

    Proportion of patients without documented progression at 6 months

    Measured: 6 months after the first infusion

Secondary outcomes (11)

  1. Immune Overall Response Rate (iORR)

    ORR using immune Response Evaluation Criteria In Solid Tumors (iRECIST)

    Measured: Through study completion, an average 1 year

  2. Clinical Benefit Rate (CBR)

    CBR at 8 and 16 weeks defined as the number of non-progressors using RECIST 1.1 and iRECIST criteria

    Measured: up to 4 months

  3. Tumor Growth Rate (TGR) before and under treatment

    Percentage of variation in TGR

    Measured: up to 2 months

  4. Progression Free Survival (PFS)

    Time elapsed from the date of first infusion to the date of documented progression or death

    Measured: Through study completion, an average 1 year

  5. Overall Survival (OS)

    Time elapsed from the date of first infusion to the date of death

    Measured: Through study completion, an average 1 year

  6. Incidence of Serious Adverse Event (SAE) and Treatment Emergent Adverse Event (TEAE)

    Number of events

    Measured: Through study completion, an average 1 year

  7. Pharmacodynamics evaluation

    Tumor Immune MicroEnvironment analysis and evolution changes: quantity/density and quality of immune cells

    Measured: Up to 2 months

  8. Exposure to murlentamab

    PK parameters analysis

    Measured: At days 1 and 15 of cycles 1, 2 (each cycle is 28 days) and End of Treatment for cohort I and II, an average of one year; days 1, 8,15 and 22 of cycles 1, 2 (each cycle is 28 days) and End of Treatment for cohort II expansion, an average of one year

  9. Exposure to trifluridine

    Trifluridine plasma concentrations only for cohort II

    Measured: At days 1 and 15 of cycles 1, 2 (each cycle is 28 days) and End of Treatment, an average of one year

  10. Evidence of anti-murlentamab antibodies (ADA)

    Presence of ADA

    Measured: Baseline, beginning of every even cycle in pre-dose (each cycle is 28 days) and at the End of Treatment, an average of one year

  11. AMHRII (Anti-Mullerian Hormone type II receptor) expression

    AMHRII membrane expression in percentage

    Measured: Up to 2 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jan 2019
  2. Study start11 Jul 2018
  3. Primary completion19 Jan 2021
  4. Study completion10 Feb 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
65 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03799731
Sponsor's protocol ID
C201
Status last verified
Apr 2022
First submitted
8 Jan 2019
Last updated
14 Apr 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GM102, Trifluridine/Tipiracil and GM102 expansion in people with Colorectal Cancer, run by GamaMabs Pharma at 5 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Belgium, Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: Through study completion, an average 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03799731.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2022.

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