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

Primary Purpose

Neoplasm, Gynecologic

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
GM102
GM102 escalating doses
GM102
Sponsored by
GamaMabs Pharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neoplasm, Gynecologic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Institut Bordet
  • UZ Leuven
  • CHU Besançon
  • Institut Bergonié
  • Centre Oscar Lambret
  • Centre Leon Berard
  • Institut de cancerologie de Montpellier
  • Institut de cancerologie de Lorraine
  • Institut Curie
  • Institut Universitaire Cancer Toulouse - Oncopole
  • Gustave Roussy
  • Royal Marsden Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

GM102 escalating doses

GM102 escalating doses + carboplatin+paclitaxel

GM102 recommended dose

Arm Description

8 successive cohorts

2 successive cohorts

3 parallel cohorts in sex cord stromal, epithelial ovarian and cervix cancers

Outcomes

Primary Outcome Measures

Phase I part: incidence of Dose Limiting Toxicities (DLTs)
Number of patients in the DLT evaluable population experiencing at least one DLT
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

Secondary Outcome Measures

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
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
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
Clinical benefit rate
Percentage of patients achieving Complete Response (CR), Partial Response (PR) or Stable Disease (SD) superior to 3 months
Duration of response
Duration of overall response in months for patients who achieved PR and/or CR
Time to progression (TTP)
Time from first dose received until objective tumor progression

Full Information

First Posted
November 23, 2016
Last Updated
March 27, 2022
Sponsor
GamaMabs Pharma
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1. Study Identification

Unique Protocol Identification Number
NCT02978755
Brief Title
First In Human Safety, Pharmacokinetics and Anti-tumoral Activity of GM102 in Gynecological Cancers
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
June 2016 (undefined)
Primary Completion Date
June 10, 2020 (Actual)
Study Completion Date
June 10, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GamaMabs Pharma

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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. The primary objective of the study is to determine the GM102 recommended dose.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasm, Gynecologic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
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)
Allocation
Non-Randomized
Enrollment
78 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GM102 escalating doses
Arm Type
Experimental
Arm Description
8 successive cohorts
Arm Title
GM102 escalating doses + carboplatin+paclitaxel
Arm Type
Experimental
Arm Description
2 successive cohorts
Arm Title
GM102 recommended dose
Arm Type
Experimental
Arm Description
3 parallel cohorts in sex cord stromal, epithelial ovarian and cervix cancers
Intervention Type
Drug
Intervention Name(s)
GM102
Intervention Description
GM102 escalating doses (phase1)
Intervention Type
Drug
Intervention Name(s)
GM102 escalating doses
Intervention Description
GM102 escalating doses combined with paclitaxel and carboplatin
Intervention Type
Drug
Intervention Name(s)
GM102
Intervention Description
GM102 single agent at recommended dose in 3 parallel cohorts (sex cord, epithelial ovarian, cervix cancers)
Primary Outcome Measure Information:
Title
Phase I part: incidence of Dose Limiting Toxicities (DLTs)
Description
Number of patients in the DLT evaluable population experiencing at least one DLT
Time Frame
Four weeks
Title
Phase Ib part: incidence of Serious Adverse Events (SAEs) and Treatment-Emergent Adverse Events (TEAEs) at Recommended Phase 2 Dose (RP2D)
Description
Number of patients with at least one AE
Time Frame
Through study completion, an average of 1 year
Secondary Outcome Measure Information:
Title
PK: Maximum Serum Concentration [Cmax]
Description
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
Time Frame
up to 16 weeks
Title
PK: Area Under the Curve [AUC]
Description
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
Time Frame
up to 16 weeks
Title
Response Rate using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
Description
Percentage of patients who achieved a Complete Response (CR) or a Partial Response (PR) based on RECIST version 1.1
Time Frame
Through study completion
Title
Clinical benefit rate
Description
Percentage of patients achieving Complete Response (CR), Partial Response (PR) or Stable Disease (SD) superior to 3 months
Time Frame
up to 3 months
Title
Duration of response
Description
Duration of overall response in months for patients who achieved PR and/or CR
Time Frame
Through study completion
Title
Time to progression (TTP)
Description
Time from first dose received until objective tumor progression
Time Frame
Through study completion

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexandra Leary, MD/PhD
Organizational Affiliation
Gustave Roussy center, Villejuif, France
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut Bordet
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
Country
Belgium
Facility Name
CHU Besançon
City
Besançon
Country
France
Facility Name
Institut Bergonié
City
Bordeaux
Country
France
Facility Name
Centre Oscar Lambret
City
Lille
Country
France
Facility Name
Centre Leon Berard
City
Lyon
Country
France
Facility Name
Institut de cancerologie de Montpellier
City
Montpellier
Country
France
Facility Name
Institut de cancerologie de Lorraine
City
Nancy
Country
France
Facility Name
Institut Curie
City
Paris
Country
France
Facility Name
Institut Universitaire Cancer Toulouse - Oncopole
City
Toulouse
Country
France
Facility Name
Gustave Roussy
City
Villejuif
Country
France
Facility Name
Royal Marsden Hospital
City
London
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
32503947
Citation
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.
Results Reference
derived

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

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