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.
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
78
Institut Bordet
Brussels, Belgium
UZ Leuven
Leuven, Belgium
CHU Besançon
Besançon, France
Institut Bergonié
Bordeaux, France
Phase I part: incidence of Dose Limiting Toxicities (DLTs)
Number of patients in the DLT evaluable population experiencing at least one DLT
Time frame: Four weeks
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
Time frame: Through study completion, an average of 1 year
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
Time frame: up to 16 weeks
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
Time frame: up to 16 weeks
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
Time frame: Through study completion
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Centre Oscar Lambret
Lille, France
Centre Leon Berard
Lyon, France
Institut de cancerologie de Montpellier
Montpellier, France
Institut de cancerologie de Lorraine
Nancy, France
Institut Curie
Paris, France
Institut Universitaire Cancer Toulouse - Oncopole
Toulouse, France
...and 2 more locations
Clinical benefit rate
Percentage of patients achieving Complete Response (CR), Partial Response (PR) or Stable Disease (SD) superior to 3 months
Time frame: up to 3 months
Duration of response
Duration of overall response in months for patients who achieved PR and/or CR
Time frame: Through study completion
Time to progression (TTP)
Time from first dose received until objective tumor progression
Time frame: Through study completion