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

NCT02978755 | Completed Phase 1

• 1 other identifier: C101
• Study Type: interventional
• Target: 78
• Locations: 3 countries
• Sites: 12

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.

Conditions

Neoplasm, Gynecologic

Outcome Measures

Primary Outcomes (2)

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

  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)

  Number of patients with at least one AE

  Through study completion, an average of 1 year

Secondary Outcomes (6)

• PK: Maximum Serum Concentration [Cmax]

  up to 16 weeks

• PK: Area Under the Curve [AUC]

  up to 16 weeks

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

  Through study completion

• Clinical benefit rate

  up to 3 months

• Duration of response

  Through study completion

Study Arms (3)

GM102 escalating doses

EXPERIMENTAL

8 successive cohorts

Drug: GM102

GM102 escalating doses + carboplatin+paclitaxel

EXPERIMENTAL

2 successive cohorts

Drug: GM102 escalating doses

GM102 recommended dose

EXPERIMENTAL

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

Drug: GM102

Interventions

GM102 DRUG

GM102 escalating doses (phase1)

GM102 escalating doses

GM102 escalating doses DRUG

GM102 escalating doses combined with paclitaxel and carboplatin

GM102 escalating doses + carboplatin+paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• GamaMabs Pharma: lead

Study Sites (12)

Institut Bordet

Brussels, 1000, Belgium

Location

UZ Leuven

Leuven, Belgium

Location

CHU Besançon

Besançon, France

Location

Institut Bergonié

Bordeaux, France

Location

Centre Oscar Lambret

Lille, France

Location

Centre Leon Berard

Lyon, France

Location

Institut de cancerologie de Montpellier

Montpellier, France

Location

Institut de cancerologie de Lorraine

Nancy, France

Location

Institut Curie

Paris, France

Location

Institut Universitaire Cancer Toulouse - Oncopole

Toulouse, France

Location

Gustave Roussy

Villejuif, France

Location

Royal Marsden Hospital

London, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 32503947 DERIVED

MeSH Terms

Conditions

Genital Neoplasms, Female

Condition Hierarchy (Ancestors)

Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Alexandra Leary, MD/PhD

  Gustave Roussy center, Villejuif, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: * 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

Study Record Dates

• First Submitted: November 23, 2016
• First Posted: December 1, 2016
• Study Start: June 1, 2016
• Primary Completion: June 10, 2020
• Study Completion: June 10, 2020
• Last Updated: April 6, 2022

Record last verified: 2022-03

Locations

FR (9); GB (1); BE (2)