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Neoplasm, GynecologicPhase 1NCT02978755

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

A Phase 1 study testing GM102 and GM102 escalating doses in people with Neoplasm, Gynecologic, run by GamaMabs Pharma at 12 sites in 3 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

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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Neoplasm, Gynecologic
What is being tested?
GM102 and GM102 escalating doses
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
12 sitesin 3 countries
Study dates
Jun 2016to 10 Jun 2020
Phase
Phase 1
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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.
Show all 17Show fewer
  • 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.

Trial locations and contacts

12 sites in 3 countries.

12 sites in 3 countries

France9 sites

  • CHU Besançon

    Besançon

  • Institut Bergonié

    Bordeaux

  • Centre Oscar Lambret

    Lille

  • Centre Leon Berard

    Lyon

  • Institut de cancerologie de Montpellier

    Montpellier

  • Institut de cancerologie de Lorraine

    Nancy

  • Institut Curie

    Paris

  • Institut Universitaire Cancer Toulouse - Oncopole

    Toulouse

  • Gustave Roussy

    Villejuif

Other trials in France

Belgium2 sites

  • Institut Bordet

    Brussels, 1000

  • UZ Leuven

    Leuven

Other trials in Belgium

United Kingdom1 site

  • Royal Marsden Hospital

    London

Other trials in United Kingdom

About this study

Official title: 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.

Read the 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.

Being tested
GM102, GM102 escalating doses
Medical subject headings
Genital Neoplasms, Female

What participants receive

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

  • GM102Drug

    GM102 escalating doses (phase1)

  • GM102 escalating dosesDrug

    GM102 escalating doses combined with paclitaxel and carboplatin

  • GM102Drug

    GM102 single agent at recommended dose in 3 parallel cohorts (sex cord, epithelial ovarian, cervix cancers)

Study groups in NCT02978755
Study groupRoleWhat they receive
GM102 escalating dosesExperimental8 successive cohorts
Receives: Drug: GM102
GM102 escalating doses + carboplatin+paclitaxelExperimental2 successive cohorts
Receives: Drug: GM102 escalating doses
GM102 recommended doseExperimental3 parallel cohorts in sex cord stromal, epithelial ovarian and cervix cancers
Receives: Drug: GM102

What is being measured

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

  1. Phase I part: incidence of Dose Limiting Toxicities (DLTs)

    Number of patients in the DLT evaluable population experiencing at least one DLT

    Measured: Four weeks

  2. Phase Ib part: incidence of Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events (TEAEs) at Recommended Phase 2 Dose (RP2D)

    Number of patients with at least one AE

    Measured: Through study completion, an average of 1 year

Secondary outcomes (6)

  1. PK: Maximum Serum Concentration [Cmax]

    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

    Measured: up to 16 weeks

  2. PK: Area Under the Curve [AUC]

    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

    Measured: up to 16 weeks

  3. Response Rate using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1

    Percentage of patients who achieved a Complete Response (CR) or a Partial Response (PR) based on RECIST version 1.1

    Measured: Through study completion

  4. Clinical benefit rate

    Percentage of patients achieving Complete Response (CR), Partial Response (PR) or Stable Disease (SD) superior to 3 months

    Measured: up to 3 months

  5. Duration of response

    Duration of overall response in months for patients who achieved PR and/or CR

    Measured: Through study completion

  6. Time to progression (TTP)

    Time from first dose received until objective tumor progression

    Measured: Through study completion

Timeline

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

  1. First posted1 Dec 2016 (estimated)
  2. Study startJun 2016
  3. Primary completion10 Jun 2020
  4. Study completion10 Jun 2020

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
* phase 1 escalation GM102 single agent * phase 1 escalation GM102 combined with paclitaxel and carboplatin * phase 1b: 3 parallel expansion cohorts at the recommended dose of GM102 single agent
Masking
None (open label)
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02978755
Sponsor's protocol ID
C101
Status last verified
Mar 2022
First submitted
23 Nov 2016
Last updated
6 Apr 2022
Results posted
No
Data monitoring committee
No

Publications

  • Prat M, Le Naour A, Coulson K, Lemee F, Leray H, Jacquemin G, Rahabi MC, Lemaitre L, Authier H, Ferron G, Barret JM, Martinez A, Ayyoub M, Delord JP, Gladieff L, Tabah-Fisch I, Prost JF, Couderc B, Coste A. Circulating CD14high CD16low intermediate blood monocytes as a biomarker of ascites immune status and ovarian cancer progression. J Immunother Cancer. 2020 Jun;8(1):e000472. doi: 10.1136/jitc-2019-000472.

    PubMed 32503947

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GM102 and GM102 escalating doses in people with Neoplasm, Gynecologic, run by GamaMabs Pharma at 12 sites in 3 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 8 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 6 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 12 sites in France, Belgium, United Kingdom. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Phase I part: incidence of Dose Limiting Toxicities (DLTs) (time frame: Four weeks). 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 NCT02978755, which also lists 1 linked publication.

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 6 Apr 2022.

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