AssociatiNG Bevacizumab bEmarituzumab for GynecoLogIcal CAncer

NCT07146919 | Withdrawn Phase 1 DMC

• 2 other identifiers: ET24-2242024-516724-33-00
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The aim of this study is to determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of bemarituzimab given in combination with a fixed dose of bevacizumab and to assess the clinical activity of the proposed combination bemarituzumab and bevacizumab in 3 parallel and independent cohorts of gynecological cancer (endometrium, ovary and cervix).

Conditions

Endometrial Carcinoma; Ovarian Cancer; Cervix Cancer

Keywords

Immunohistochemistry; Bemarituzumab; Bevacizumab; FGFR2b; RECIST

Outcome Measures

Primary Outcomes (2)

• Dose escalation part : Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)

  To Determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of bemarituzimab given in combination with a fixed dose of bevacizumab. Dose Limiting toxicities (DLTs) are defined specific adverse events (AEs) graded using NCI-CTCAE v5.0 or specific grading for ocular AE occurring during the DLT period and assessed as related to bemarituzumab and/or bevacizumab

  6 weeks

• Extension part : Progression free rate (PFR)

  To assess the clinical activity of the proposed combination bemarituzumab and bevacizumab in 3 parallel and independent cohorts of gynecological cancer (endometrium, ovary and cervix). PFR-12weeks is defined as the rate of patients with non-progressive disease i.e. complet response (CR)/partial response (PR)/stable disease (SD) as per RECIST v1.1. after 12 weeks of treatment.

  12 weeks

Secondary Outcomes (6)

• Best overall response rate (BORR)

  Every 6 weeks until 24 weeks post cycle 1 day 1 (each cycle is 21 days) then every 12 weeks, through study completion, an average of 5 years

• Duration of response (DoR)

  Every 6 weeks until 24 weeks post cycle 1 day 1 (each cycle is 21 days) then every 12 weeks, through study completion, an average of 5 years

• Progression-Free Survival

  Every 6 weeks until 24 weeks post cycle 1 day 1 (each cycle is 21 days) then every 12 weeks, through study completion, an average of 5 years

• Overall Survival

  Until up to 1 year follow-up of the last patient enrolled

• Adverse events

  from the date of first intake of study drug until 100 days after study drug discontinuation, (at least up to 12 months for the last patient in)

Study Arms (3)

Patient with endometrial cancer

EXPERIMENTAL

Patients must have histologically or cytologically confirmed locally advanced or metastatic endometrial carcinoma (endometroid, serous, carcinosarcoma and undifferentiated or clear cell carcinoma), uterine neuroendocrine carcinoma and uterine sarcoma are not eligible, and with a gynecological cancer overexpressed FGFR2b by immunohistochemistry testing.

Drug: Bemarituzumab; Drug: Bevacizumab

Patient with ovarian cancer

EXPERIMENTAL

Patients must have histologically or cytologically confirmed locally advanced or metastatic high grade ovarian cancer patients (endometrioid, serous, clear cell, carcinosarcoma), platinum resistant and with a gynecological cancer overexpressed FGFR2b by immunohistochemistry testing.

Drug: Bemarituzumab; Drug: Bevacizumab

Patient with cervix cancer

EXPERIMENTAL

Patients must have histologically or cytologically confirmed locally advanced or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix and with a gynecological cancer overexpressed FGFR2b by immunohistochemistry testing.

Drug: Bemarituzumab; Drug: Bevacizumab

Interventions

Bemarituzumab DRUG

Part 1 Dose escalation part : IV infusion, every 3 weeks with the dose : DL1 = 15 mg/kg cycle 1 day 1, then 11 mg/kg thereafter from cycle 2 day 1 DL2 = 22 mg/kg cycle 1 day 1, then 15 mg/kg thereafter from cycle 2 day 1 DL3 = 30 mg/kg cycle 1 day 1, then 22 mg/kg thereafter from cycle 2 day 1 Part 2 Extension part : IV infusion, every 3 weeks with the dose defined in the phase I dose escalation Treatment with both study drugs will continue until disease progression according to RECIST v1.1, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurs first

Patient with cervix cancer; Patient with endometrial cancer; Patient with ovarian cancer

Bevacizumab DRUG

IV infusion, 15mg/kg, every 3 weeks. Treatment with both study drugs will continue until disease progression according to RECIST v1.1, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurs first

Patient with cervix cancer; Patient with endometrial cancer; Patient with ovarian cancer

Eligibility Criteria

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

You may qualify if:

• I1. Female patients ≥ 18 years of age at time of ICF signature.
• I2. Patients must have histologically or cytologically confirmed locally advanced or metastatic gynaecological cancer including
• Cohort I - all endometrial carcinoma (endometroid, serous, carcinosarcoma and undifferentiated or clear cell carcinoma). Uterine neuroendocrine carcinoma and uterine sarcoma are not eligible.
• Cohort II - high grade ovarian cancer patients (endometrioid, serous, clear cell, carcinosarcoma), platinum resistant. Note 1: Patients who have only had 1 prior line of platinum based therapy must have received at least 4 cycles of platinum, must have had a response (complete response/remission \[CR\] or partial response/remission \[PR\]) and then progressed between \> 3 months and ≤ 6 months after the date of the last dose of platinum; patients who have received 2 or 3 prior lines of platinum therapy must have progressed on or within 6 months after the date of the last dose of platinum; patients allergic to platinum and unable to reintroduce platinum despite a desensitisation technique are eligible. Beyond 3 prior lines, no specific requirements about PD on platinum. Note 2: Platinum-Resistant Ovarian Cancer (PROC) with high folate receptor-alpha expression should have received mirvetuximab soravtansine if reimbursed before to be included.
• Cohort III - squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix.
• I3. Previously treated by at least one previous line of platinum-based therapy but no more than 5 lines of systemic therapies (maintenance treatment is not considered as a line of treatment). Note 1- Previous bevacizumab\* is allowed except if therapy was stopped for bevacizumab-related grade 3 or 4 adverse events. Note 2 - Required prior treatment, except in case of major contraindication:
• For BRCA mutated ovarian cancer: PARP inhibitor
• For CPS≥10 cervical cancer : immunotherapy
• For dMMR endometrial carcinoma : immunotherapy
• For pMMR recurrent endometrial carcinoma : immunotherapy
• I4. Documented FGFR2b overexpressing tumor as determined by IHC test on tumor sample either archival or a fresh biopsy. Note - Molecular screening should be initiated during an ongoing therapy line, i.e. before documented progression.
• I5. Documented disease progression and at least one measurable lesion that can be accurately assessed at baseline by computed tomography (CT) or magnetic resonance imaging \[MRI\] and is suitable for repeated assessment as per RECIST v1.1.
• I6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• I7. Adequate organ and marrow function with following lab values within 7 days before C1D1:
• absolute neutrophil count (ANC) ≥1.5 \* 109/L,

You may not qualify if:

• E1. Patient with ocular related disorders:
• Presence or history of systemic disease or ophthalmologic disorders requiring chronic use of ophthalmic steroids.
• Evidence of any ongoing ophthalmologic abnormalities or symptoms that are acute (within 4 weeks) or are actively progressing.
• Unwillingness to avoid use of contact lenses during study treatment and for ≥ 100 days after the end of treatment.
• Recent (within 6 months) corneal surgery or ophthalmic laser treatment or corneal defects, corneal ulcerations, keratitis, or keratoconus, or other known abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer.
• E2. Evidence or treatment for another active malignancy within 3 years prior to study entry. Curatively treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia is allowed.
• E4. Untreated or symptomatic central nervous system (CNS) metastases or leptomeningeal disease.
• NOTE - Patients with asymptomatic CNS metastases are eligible if clinically stable for ≥ 4 weeks and require no intervention (including use of corticosteroids).
• Subjects with treated brain metastases are eligible provided the following criteria are met:
• Definitive therapy was completed ≥ 2 weeks before the first planned dose of study treatment (stereotactic radiosurgery ≥ 7 days before C1D1),
• Any CNS disease is clinically stable, patient is off steroids for CNS disease (unless steroids are indicated for a reason unrelated to CNS disease), and patient is off (or on stable doses of) antiepileptic agents ≥ 7 days prior to C1D1.
• E5. Use or expected need of prohibited concomitant medications or procedures or no respect of the wash out period listed below:
• Any investigational agent or approved anti-cancer therapy within 4 weeks prior to C1D1.
• Within 10 days prior to C1D1 for the following treatment: acetylsalicylic acid (\> 325 mg/day); clopidogrel (\> 75 mg/day); Therapeutic oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes except if INR or aPTT is within therapeutic limits (according to the medical standard of the enrolling institution) and the patient has been on a stable dose of anticoagulants for at least 2 weeks at C1D1.
• Live or live-attenuated vaccine within 30 days prior to the first dose of study drug. Note: killed vaccine sare allowed. Vaccination with a live or live-attenuated vaccines will not be allowed during therapy. Subjects enrolled in this study are permitted to receive vaccinations for COVID-19, however, vaccination should not be administered within 2 days before or after bemarituzumab infusion.

Sponsors & Collaborators

• Centre Leon Berard: lead

MeSH Terms

Conditions

Endometrial Neoplasms; Ovarian Neoplasms; Uterine Cervical Neoplasms

Interventions

bemarituzumab; Bevacizumab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Cervical Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

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

Model Details: The dose escalation will be conducted according to a sequential and adaptive Bayesian scheme, using the method of TITE-CRM to determine the MTD of bemarituzumab in combination with a fixed dose of bevacizumab. This method allows continual accrual (i.e. the study will be opened to accrual continually) throughout the trial while using the 6-week toxicity endpoint as basis of dose escalation. Dose allocation will be centrally defined, before each inclusion considering the DLT observed in all patients previously evaluated, and the current toxicity status of patients who have not received a full 2-cycle treatment (i.e. DLT period is still ongoing). After the dose escalation part, study will be opened with 87 patients (including patients from the dose escalation part) at DL1, DL2 or DL3

Study Record Dates

• First Submitted: August 14, 2025
• First Posted: August 28, 2025
• Study Start: October 15, 2025
• Primary Completion (Estimated): October 15, 2030
• Study Completion (Estimated): October 15, 2030
• Last Updated: April 23, 2026

Record last verified: 2026-04