First In Human Safety, Pharmacokinetics and Anti-tumoral Activity of GM102 in Gynecological Cancers

March 27, 2022 updated by: GamaMabs Pharma

Open, Non Controlled, Multicenter, First-in-Human Study for the Evaluation of the Safety, Pharmacokinetics and Preliminary Antitumor Activity of GM102 in Patients With Advanced Pretreated Gynecological Cancer

First in Human study, assessing the safety profile, the pharmacokinetics and preliminary antitumor activity of GM102, a new compound (a monoclonal antibody), in patients with previously treated gynecological cancers bearing the AMHRII (anti-mullerian Hormone Receptor II) receptor. The primary objective of the study is to determine the GM102 recommended dose.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

AMHRII, an embryonic receptor, is reexpressed in a subset of gynecological cancers. GM102 is a humanized low fucose monoclonal antibody with a high affinity to AMHRII receptor. GM102 acts through enhanced capability to engage immune effector cells (macrophages, natural killer (NK) cells) to trigger ADCC (antibody dependent cellular cytotoxicity) and phagocytosis of tumor cells.

Patients with gynecological tumors expressing AMHRII receptor on the tumor cells in archived tissue as determined prior to study entry will be eligible for C101 study.

C101 consists in a phase I part (dose and schedule escalation) and a phase Ib part (expansion).

The phase I part is designed to determine the recommended phase 2 dose (RP2D) using the classical 3+3 dose-finding design. In six successive escalating dose cohorts, patients will receive GM102 infusions every 2 weeks until progression or toxicity. In 4 additional cohorts, patients will receive GM102 infusions weekly until progression or toxicity and GM102 infusions combined with chemotherapy until progression or toxicity.

A Trial Steering Committee (TSC) will analyze and qualify the toxicities and will provide recommendations according to the dose administration rules defined in the protocol.

At the end of the phase I part, the RP2D will be determined, taking into account dose limiting toxicities (DLTs), overall toxicity, pharmacokinetics and pharmacodynamic effects of GM102.

The Phase Ib part of the study will confirm the tolerance of the selected dose (RP2D) and will assess antitumoral activity of GM102 in three parallel cohorts of patients with Sex Cord-Stromal tumors, and AMHRII positive ovarian and cervix cancers. Patients will be treated until progression or toxicity.

Study Type

Interventional

Enrollment (Actual)

78

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium, 1000
        • Institut Bordet
      • Leuven, Belgium
        • UZ Leuven
  • France
      • Besançon, France
        • CHU Besancon
      • Bordeaux, France
        • Institut Bergonie
      • Lille, France
        • Centre Oscar Lambret
      • Lyon, France
        • Centre Leon Berard
      • Montpellier, France
        • Institut de Cancérologie de Montpellier
      • Nancy, France
        • Institut de cancerologie de Lorraine
      • Paris, France
        • Institut Curie
      • Toulouse, France
        • Institut Universitaire Cancer Toulouse - Oncopole
      • Villejuif, France
        • Gustave Roussy
  • United Kingdom
      • London, United Kingdom
        • Royal Marsden Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Locally advanced, or metastatic recurrent gynecological cancer, for whom no standard alternative therapy is available, having received at least one line of therapy and expressing AMHRII on tumor cells.
  • If possible at least one lesion should be identified for 2 biopsies: a baseline biopsy and an under-treatment biopsy for AMHRII expression and GM102 pharmacodynamics evaluation.
  • Available tumor block or at least 10 slides from formalin-fixed paraffin-embedded (FFPE) archival tissue.
  • At least one measurable lesion by RECIST (Response Evaluation Criteria in Solid Tumors) on screening CT-scan.
  • Written Informed Consent forms.
  • Willing and able to comply with the trial requirements.
  • Covered by healthcare insurance in accordance with local requirements.

For phase 1b, only patients with either Sex cord stromal tumors or epithelial ovarian cancer or cervix cancer will be eligible

Exclusion Criteria:

  • Age < 18 years old.
  • Eastern Cooperative Oncology Group (ECOG) performance status > 1
  • Life expectancy < 12 weeks.
  • 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.
  • Concurrent chronic corticosteroid treatment.
  • Known severe anaphylactic or other hypersensitivity reactions secondary to a prior exposure to human antibodies or to any protein product.
  • Washout period before treatment initiation: < 3 weeks or 5 times the half-life, whichever is shorter, for prior antitumor therapy (small molecules and/or antibody-drug conjugates, radiotherapy) or 6 weeks for monoclonal antibodies.
  • Any active concomitant malignancy.
  • 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 neutrophils < 1.0 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: left ventricular ejection fraction ≤ 40%, serum creatinine > 1.5 x upper limit of normal (ULN), total bilirubin > 1.5 x ULN, AST and ALT> 2.5 x ULN in the absence of liver metastasis or > 5 x ULN in case of documented liver metastasis.
  • Non-resolution of any prior treatment related toxicity to < Grade 2, except for alopecia according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03.
  • Pregnancy or breastfeeding.
  • Patient with reproductive potential who do not agree to use an accepted effective method of contraception - investigator's judgment - during the study period and for at least 4 months following completion of study treatment.
  • Patient participating in another clinical trial investigating a treatment during the study and within 30 days prior to first study treatment administration.
  • Patient deprived of her liberty by a judicial or administrative decision, patient admitted to a hospital, social institution or who is under a measure of legal protection, patient hospitalized without consent or who is in an emergency situation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GM102 escalating doses
8 successive cohorts
Drug: GM102
GM102 escalating doses (phase1)
Drug: GM102
GM102 single agent at recommended dose in 3 parallel cohorts (sex cord, epithelial ovarian, cervix cancers)
Experimental: GM102 escalating doses + carboplatin+paclitaxel
2 successive cohorts
Drug: GM102 escalating doses
GM102 escalating doses combined with paclitaxel and carboplatin
Experimental: GM102 recommended dose
3 parallel cohorts in sex cord stromal, epithelial ovarian and cervix cancers
Drug: GM102
GM102 escalating doses (phase1)
Drug: GM102
GM102 single agent at recommended dose in 3 parallel cohorts (sex cord, epithelial ovarian, cervix cancers)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase I part: incidence of Dose Limiting Toxicities (DLTs)
Time Frame: Four weeks
Number of patients in the DLT evaluable population experiencing at least one DLT
Four weeks
Phase Ib part: incidence of Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events (TEAEs) at Recommended Phase 2 Dose (RP2D)
Time Frame: Through study completion, an average of 1 year
Number of patients with at least one AE
Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PK: Maximum Serum Concentration [Cmax]
Time Frame: up to 16 weeks
Cycle 1 Day 1 pre-dose, Cycle 1 Day 1 End Of Infusion (EOI), Cycle 1 Day 1 EOI + 3 hours, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 8, Cycle 1 Day 15 pre-dose, Cycle 1 Day 15 EOI, Cycle 2 Day 1 pre-dose, Cycle 2 Day 1 EOI, Cycle 2 Day 15 pre-dose, Cycle 2 Day 15 EOI, Cycle 3 Day 1 pre-dose, Cycle 3 Day 1 EOI, Cycle 3 Day 15 pre-dose, Cycle 3 Day 15 EOI, Cycle 4 Day 1 pre-dose, Cycle 4 Day 1 EOI, Cycle 4 Day 15 pre-dose, Cycle 4 Day 15 EOI
up to 16 weeks
PK: Area Under the Curve [AUC]
Time Frame: up to 16 weeks
Cycle 1 Day 1 pre-dose, Cycle 1 Day 1 End Of Infusion (EOI), Cycle 1 Day 1 EOI + 3 hours, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 1 Day 8, Cycle 1 Day 15 pre-dose, Cycle 1 Day 15 EOI, Cycle 2 Day 1 pre-dose, Cycle 2 Day 1 EOI, Cycle 2 Day 15 pre-dose, Cycle 2 Day 15 EOI, Cycle 3 Day 1 pre-dose, Cycle 3 Day 1 EOI, Cycle 3 Day 15 pre-dose, Cycle 3 Day 15 EOI, Cycle 4 Day 1 pre-dose, Cycle 4 Day 1 EOI, Cycle 4 Day 15 pre-dose, Cycle 4 Day 15 EOI
up to 16 weeks
Response Rate using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
Time Frame: Through study completion
Percentage of patients who achieved a Complete Response (CR) or a Partial Response (PR) based on RECIST version 1.1
Through study completion
Clinical benefit rate
Time Frame: up to 3 months
Percentage of patients achieving Complete Response (CR), Partial Response (PR) or Stable Disease (SD) superior to 3 months
up to 3 months
Duration of response
Time Frame: Through study completion
Duration of overall response in months for patients who achieved PR and/or CR
Through study completion
Time to progression (TTP)
Time Frame: Through study completion
Time from first dose received until objective tumor progression
Through study completion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

GamaMabs Pharma

Investigators

  • Principal Investigator: Alexandra Leary, MD/PhD, Gustave Roussy center, Villejuif, France

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2016

Primary Completion (Actual)

June 10, 2020

Study Completion (Actual)

June 10, 2020

Study Registration Dates

First Submitted

November 23, 2016

First Submitted That Met QC Criteria

November 30, 2016

First Posted (Estimate)

December 1, 2016

Study Record Updates

Last Update Posted (Actual)

April 6, 2022

Last Update Submitted That Met QC Criteria

March 27, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C101

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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