First In Human Safety, Pharmacokinetics and Anti-tumoral Activity of GM102 in Gynecological Cancers
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|ClinicalTrials.gov Identifier: NCT02978755|
Recruitment Status : Active, not recruiting
First Posted : December 1, 2016
Last Update Posted : July 31, 2019
|Condition or disease||Intervention/treatment||Phase|
|Neoplasm, Gynecologic||Drug: GM102 Drug: Paclitaxel + carboplatin||Phase 1|
AMHRII 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 of 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 pharmacodynamics 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 (Clinical Trial)|
|Actual Enrollment :||78 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||
|Masking:||None (Open Label)|
|Official Title:||Open, Non Controlled, Multicenter, Firs-in-human Study for the Evaluation of the Safety, Pharmacokinetics and Preliminary Antitumor Activity of GM102 in Patients With Advanced Pretreated Gynecological Cancer|
|Study Start Date :||June 2016|
|Estimated Primary Completion Date :||March 30, 2020|
|Estimated Study Completion Date :||March 30, 2020|
Experimental: GM102 escalating doses
8 successive cohorts
GM102 escalating doses (phase1)
Experimental: GM102 escalating doses + carboplatin+paclitaxel
2 successive cohorts
Drug: Paclitaxel + carboplatin
GM102 escalating doses combined with paclitaxel and carboplatin
Experimental: GM102 recommended dose
3 parallel cohorts in sex cord stromal, epithelial ovarian and cervix cancers
GM102 single agent at recommended dose in 3 parallel cohorts (sex cord, epithelial ovarian, cervix cancers)
- Phase I part: incidence of Dose Limiting Toxicities (DLTs) [ 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) [ Time Frame: Through study completion, an average of 1 year ]
- 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
- 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
- Response Rate using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 [ Time Frame: Through study completion, an average of 1 year ]
- Clinical benefit rate defined as percentage of patients achieving Complete Response (CR), Partial Response (PR) or Stable Disease (SD) superior to 3 months [ Time Frame: up to 3 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02978755
|Brussels, Belgium, 1000|
|Centre Oscar Lambret|
|Centre Leon Berard|
|Institut de cancerologie de Montpellier|
|Institut de cancerologie de Lorraine|
|Institut Universitaire Cancer Toulouse - Oncopole|
|Royal Marsden Hospital|
|London, United Kingdom|
|Principal Investigator:||Alexandra Leary, MD/PhD||Gustave Roussy center, Villejuif, France|