Safety and Efficacy of Ubamatamab With First-line Chemotherapy in Ovarian Cancer (RegeNovar)

A Phase I/II Study of Ubamatamab Plus Carboplatin, Paclitaxel, and Bevacizumab as Salvage Therapy in Ovarian Cancer With Poor Response to First-Line Chemotherapy

The purpose of this clinical trial is to assess the safety and efficacy of ubamatamab in combination with first-line chemotherapy in patients with ovarian cancer. The main questions it aims to answer are:

• What is the safety profile of ubamatamab when administered with carboplatin-paclitaxel ± bevacizumab?
• What is the objective response rate after three cycles of ubamatamab in combination with carboplatin-paclitaxel ± bevacizumab?

Participants will:

• Receive three cycles of ubamatamab in combination with carboplatin-paclitaxel ± bevacizumab, followed by maintenance therapy with ubamatamab ± bevacizumab for up to 15 months, depending on HRD status and disease response after the initial treatment cycles.
• Attend regular clinic visits throughout the treatment period for checkups and tests

Study Overview

• Status: Not yet recruiting
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: Ubamatamab; Drug: Chemotherapy; Drug: Bevacizumab; Drug: GCSF

• Study Type: Interventional
• Enrollment (Estimated): 43
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Mihary ANDRIAMAMONJY; Phone Number: 01 84 85 20 09; Email: mandriamamonjy@arcagy.org

Study Locations

• France
  • Bordeaux, France, 33076
    • Institut Bergonie
    • Principal Investigator: Coriolan Lebreton
  • Caen, France, 14076
    • Centre François Baclesse
    • Principal Investigator: Coraline DUBOT POITELON
  • Dijon, France, 21079
    • Centre Georges François Leclerc
    • Principal Investigator: Leïla BENGRINE LEFEVRE
  • Lyon, France, 69373
    • Centre Leon Berard
    • Principal Investigator: Brunhilde HANVIC
  • Marseille, France, 13273
    • Institut Paoli Calmettes
    • Principal Investigator: Renaud SABATIER
  • Montpellier, France, 34298
    • ICM Val d'Aurelle
    • Principal Investigator: Stanislas QUESADA
  • Pierre-Bénite, France, 69495
    • HCL - Centre Hospitalier Lyon Sud
    • Principal Investigator: Benoit YOU
  • Rennes, France, 35042
    • Centre Eugène Marquis
    • Principal Investigator: Thibault DE LA MOTTE ROUGE
  • Saint-Herblain, France, 44805
    • ICO - Centre René Gauducheau
    • Principal Investigator: Jean-Sébastien FRENEL
  • Strasbourg, France, 67098
    • Hopital de Hautepierre
    • Principal Investigator: Laurianne EBERST
  • Villejuif, France, 94805
    • Gustave Roussy
    • Principal Investigator: Alexandra LEARY

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed high-grade epithelial (serous, endometrioid, or carcinosarcoma with a ≥30% epithelial tumor component) ovarian, primary peritoneal, or fallopian-tube carcinoma
2. Adult patient aged ≥ 18 years old
3. Advanced stage III or IV

4. Treated with 3 or 4 standard neo-adjuvant cycles of carboplatin-paclitaxel regimen, in first line, given every 3 weeks, and characterized by 2 unfavorable features (both are required):

   • A poorly chemosensitive disease defined by an unfavorable standardized KELIM score < 1.0 calculated on CA-125 KELIM™ calculator for patients treated with neo-adjuvant chemotherapy
   • A disease considered not amenable to complete interval cytoreductive surgery with no post-operative macroscopic residual lesion (either because the interval cytoreductive surgery attempt was incomplete CC2-CC3, or because the surgeon considers a complete interval cytoreductive surgery is not achievable based on imaging and/or laparoscopic explorations)
5. Disease measurable and assessable by imaging based on RECIST 1.1 criteria (thorax-abdomen-pelvis CT-scanner; FDG-PET-CT-scanner; and/or MRI)
6. Availability of a tumor tissue for translational research (archival tissue, or alternatively from fresh biopsy, and/or surgery)
7. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
8. BRCA and HRD status known, or planned during the trial (before maintenance treatment)

9. Adequate bone marrow function

   • Red blood cells: baseline Hemoglobin ≥8 g/dL (without red blood cell transfusion within 3 weeks before the blood work)
   • White blood cells: Absolute neutrophil count (ANC) ≥1500 cells/mm3
   • Platelets: Platelet count ≥100,000/mm3

10. Adequate renal and liver functions

    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN), or ≤5 × ULN in context of liver metastases
    • Total bilirubin ≤1.5 × ULN (patients with Gilbert's are eligible if total bilirubin ≤3 × ULN)
    • Albumin ≥3 g/dL
    • Creatinine clearance ≥40 mL/min/1.73 m2 (measured or estimated, ideally with CKD-EPI formula on https://www.kidney.org/professionals/kdoqi/gfr_calculator )
11. Adequate heart function: LVEF ≥ 50%, measured by echocardiogram, and troponin levels above the upper limit of normal (ULN). The case of troponin level comprised between 1.0 and 2 ULN, inclusion may be discussed after cardiological assessment.
12. Life expectancy of at least 3 months
13. Patients who gave their written informed consent to participate to the study
14. Patients affiliated to a social insurance regime
15. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow-up.

Non-inclusion Criteria:

1. Low-grade endometrioid, clear cell, mucinous, or sarcomatous histology, or mixed tumors containing any of these histologies, or low-grade or borderline ovarian tumor.
2. Patients with primary platinum-refractory disease, defined as disease that has radiologically progressed during the neo-adjuvant chemotherapy
3. Contraindication to ubamatamab
4. Contraindication to carboplatin, paclitaxel or bevacizumab
5. Previous treatment with bevacizumab during initial standard neo-adjuvant chemotherapy
6. Prior treatment with anti-PD-1 therapies or T-cell therapies, or any other experimental anti-cancer systemic therapy
7. Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 2 years.

8. All trial participants with brain metastases, except those meeting the following criteria (all criteria are required):

   1. Brain metastases that have been treated locally, and are clinically asymptomatic for at least 4 weeks prior to enrolment,
   2. No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable).
   3. Trial participants with brain metastases must be either off steroids except a stable or decreasing dose of <10mg daily prednisone (or equivalent).
9. Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent
10. Patients receiving any systemic chemotherapy, radiotherapy (except for symptomatic/palliative reasons), within 3 weeks before the first dose of ubamatamab. The patient can receive a stable dose of bisphosphonates for bone metastases, before and during the study if these were started at least 4 weeks prior to treatment with study drug.
11. Persistent toxicities (≥CTCAE grade 3), caused by previous cancer therapy
12. Treatment with other investigational agents.
13. Bowel occlusive syndrome, inflammatory bowel disease, immune colitis, or other gastro-intestinal disorder that does not allow oral medication, such as malabsorption.
14. Clinically significant (i.e., active) and severe cardiovascular disease according to investigator opinion such as myocardial infarction (< 6 months prior to enrollment); any history of myocarditis; significant arrhythmia including paroxysmal atrial fibrillation requiring intervention at any time or implantation of a pacemaker or defibrillator; signs or symptoms of active angina; arrhythmia or heart failure; LEVF < 50% with echocardiogram; QTc (Friedericia) interval >470 msec (in cases of asymptomatic prolonged QTc interval (>470 msec), the ECG can be repeated up to 2 times. If subsequent QTc interval is <470 msec, the patient may be enrolled but only after review and approval by a cardiologist); Evidence of Second-Degree AV block type II (Mobitz type II) or AV block type III (complete heart block); Baseline serum troponin above institutional upper limit of normal. In cases of minimally elevated troponin in absence of clinical symptoms, after clearance by a cardiologist, the patient may be enrolled.
15. Untreated pulmonary embolism (PE) or deep vein thrombosis (DVT), not currently managed with anticoagulant therapy. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immunological adverse events. The following are not exclusionary: vitiligo, childhood asthma that has resolved, hypothyroidism that required only hormone replacement, type 1 diabetes or psoriasis that does not require systemic treatment

16. Uncontrolled infection with human immunodeficiency virus, hepatitis B or hepatitis C infection; or diagnosis of immunodeficiency or known latent tuberculosis infection.

    Participants will be tested for HCV and HBV at screening per Section 5.2

    • Patients with HIV who have controlled infection (undetectable viral load and CD4 count above 350 either spontaneously or on a stable antiviral regimen) are permitted.
    • Patients with hepatitis B surface antigen positive (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection AND receiving antiviral therapy for hepatitis B) are permitted.
    • Participants with HBsAg negative but total HBV core antibody positive (HBc Ab+) are permitted with the following requirements: If serum HBV DNA PCR is above the limit of detection at screening, antiviral therapy for HBV must be initiated prior to study entry. If serum HBV DNA PCR is below the limit of detection periodic monitoring of HBsAg must be performed.
    • Patients who are Hepatitis C virus antibody positive (HCV Ab +) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.
17. Other active infections requiring hospitalization or IV anti-infectives within 2 weeks before starting study treatment.
18. Receipt of a live vaccine within 30 days of planned start of study medication.
19. Pregnant or lactating patients or patients expecting to conceive children within the projected duration of the trial.

20. Women of childbearing potential (WOCBP)* who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose. Highly effective contraceptive measures include:

    1. stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening
    2. intrauterine device (IUD); intrauterine hormone-releasing system (IUS)
    3. bilateral tubal occlusion/ligation
    4. vasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the study participant and that the vasectomized partner has obtained medical assessment of surgical success for the procedure) and/or e. sexual abstinence** *** * WOCBP are defined as women who are fertile following menarche until becoming postmenopausal, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.

    A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to determine the occurrence of a postmenopausal state. The above definitions are according to Clinical Trial Facilitation Group (CTFG) guidance.

    ** Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient.

    ***Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of contraception. Female condom and male condom should not be used together.

21. Known psychiatric disorder that would interfere with trial compliance.
22. Patient deprived of liberty, under guardianship, or under curatorship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Carboplatin-paclitaxel-bevacizumab + ubamatamab; All participants will receive 3 cycles of the combination carboplatin-paclitaxel-bevacizumab + ubamatamab. After the 3 cycles, they will undergo surgery if it is feasible. Subsequently, they will receive maintenance treatment: ubamatamab + bevacizumab: for participants with BRCA wild-type and HRD negative tumors and for participants with a disease characterized by a BRCA mutation, or HRD positive status, and experiencing stable disease during the chemotherapy; Olaparib + bevacizumab (standard of care): for participants with a disease characterized by a BRCA mutation, or HRD-positive status, and experiencing complete or partial response during the chemotherapy.

Drug: Ubamatamab; Dosage form: Solution for perfusion Dosage: 5 mg/mL; 50 mg/mL Frequency: administration every three weeks Treatment duration: 15 months; Drug: Chemotherapy; Carboplatin + Paclitaxel administered at each cycle of 21 days (in total 3 cycles).; Drug: Bevacizumab; Bevacizumab administered at each cycle of 21 days (3 cycles in total) then during maintenance therapy every 3 weeks.; Drug: GCSF; Administered at each cycle during the 3 first cycles of the drug combination (chemotherapy + bevacizumab + ubamatamab).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety run-in phase I : Safety and recommended dose for phase II trial during the Dose-limiting toxicities monitoring period	Incidence of Treatment emergent adverse events according to NCI CTCAE version 6.0 (Safety and Tolerability)	Up to 4 weeks of treatment
Safety run-in phase I : Safety and recommended dose for phase II trial during the Dose-limiting toxicities monitoring period	Dose-limiting toxicities (DLT) occurring during the DLT period (Safety and Tolerability)	Up to 4 weeks of treatment
Safety run-in phase I : Safety and recommended dose for phase II trial during the Dose-limiting toxicities monitoring period	The recommended dose for phase II trial (RP2D) of ubamatamab in combination with carboplatin-paclitaxel + bevacizumab	From Cycle 1 Day 1 of the first patient included to Cycle 3 Day 1 of the sixth patient included (each cycle is 21 days) (Safety and Tolerability)
Efficacy phase II part	Objective response rate (ORR): Percentage of patients experiencing complete (CR) or partial response (PR) as the best overall radiological response after 3 cycles of ubamatamab in combination with carboplatin-paclitaxel-bevacizumab based on RECIST 1.1 criteria	1 month after Cycle 3 Day 1 of the sixth patient included (each cycle is 21 days).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety during the whole treatment period	Incidence of Treatment emergent Adverse events according to NCI CTCAE version 6.0 during the whole treatment period (Safety and Tolerability)	From study treatment start to 90 days after the last dose of ubamatamab
Objective response rate (ORR)	Percentage of patients experiencing complete (CR) or partial response (PR) as the best overall radiological response during the whole study treatment period based on RECIST 1.1 criteria.	Through study treatment completion, an average of 15 months.
Duration of response in patients experiencing an objective response	Time from first objective response to first objective documented disease progression (based on RECIST v1.1 criteria), or to death (regardless of the cause in the absence of disease progression).	From study treatment start to disease progression or death whichever occurs first assessed up to 48 months.
Disease control rate (DCR)	Percentage of patients experiencing complete (CR) or partial response (PR) or stable disease (SD) as the best overall radiological response during the whole treatment period based on RECIST 1.1 criteria.	From study treatment start to end of treatment, an average of 15 months.
Percentage of patients operated with late cytoreductive surgery	To determine the percentage of patients operated with late cytoreductive surgery (after 3 cycles of the study regimen), and among them the percentage of patients operated with complete surgery without any macroscopic residual lesion. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable RECIST assessment.	After 3 cycles of treatment (each cycle is 21 days).
Progression-free survival (PFS)	Time from treatment start until the date of event defined as the first objective documented disease progression (based on RECIST v1.1 criteria) or death (regardless of the cause in the absence of progression).	From study treatment start to disease progression or death whichever occurs first assessed up to 48 months.
Overall survival (OS)	Time from the date from treatment start until death regardless of the cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.	From study treatment start to death or end of study whichever occurs first assessed up to 48 months.
Progression-free survival during subsequent line of treatment (PFS-ST)	Time from the start of the subsequent line of treatment until the date of event defined as the first objective documented progression (based on RECIST v1.1), or death (regardless of the cause in the absence of progression).	From new treatment start to progression or death whichever occurs first assessed up to 48 months.

Collaborators and Investigators

• Sponsor: ARCAGY/ GINECO GROUP
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Principal Investigator: Benoit YOU, HCL - Centre Hospitalier Lyon Sud

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): April 1, 2030

Study Registration Dates

• First Submitted: January 14, 2026
• First Submitted That Met QC Criteria: June 4, 2026
• First Posted (Actual): June 10, 2026

Study Record Updates

• Last Update Posted (Actual): July 10, 2026
• Last Update Submitted That Met QC Criteria: July 9, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: chemotherapy; poor prognostic; unfavorable primary chemosensitivity; incomplete debulking surgery; KELIM
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Ovarian Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Bevacizumab; Drug Therapy
• Other Study ID Numbers: GINECO-OV133b; 2025-524232-20-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes