Phase 3 Study of Paclitaxel-Carboplatin-Oregovomab vs. Paclitaxel-Carboplatin-Placebo in Advanced Epithelial Ovarian, Fallopian Tube, or Peritoneal Carcinoma

Trial ID: 2024-519218-30-00
Protocol: QPT-ORE-005
Sponsor: Canariabio Inc.

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Diseases & Conditions

Malignant peritoneal neoplasm Fallopian tube cancer Ovarian cancer

Objectives

The primary objective of this study is to determine the efficacy of **oregovomab** in comparison to placebo, as measured by progression-free survival (PFS). This is assessed using investigator evaluations of scans according to RECIST v1.1 criteria. The study targets subjects with newly diagnosed advanced epithelial ovarian, fallopian tube, or peritoneal carcinoma (FIGO Stage III or IV) who have undergone optimal debulking surgery. The clinical relevance of this objective lies in its potential to improve PFS, a critical endpoint in the management of advanced ovarian cancer, which could lead to enhanced treatment strategies and patient outcomes.

Secondary objectives include:

Determining the efficacy of oregovomab compared to placebo by overall survival when administered with background chemotherapy (paclitaxel/carboplatin).
Assessing the safety and tolerability of oregovomab compared to placebo under the same conditions.
Evaluating the effects of treatment on Health-related Quality of Life (HRQoL) using the trial outcome index (TOI) of the Functional Assessment of Cancer Therapy – Ovarian (FACT-O) and additional questions from the NFOSI-18.

Participants

The clinical trial involves a total of **618 participants** who are exclusively female, as the study focuses on individuals with newly diagnosed **advanced epithelial ovarian, fallopian tube, or peritoneal carcinoma**. The age range of participants is 18 years and older, ensuring that all are adults. Participants were selected based on specific inclusion criteria, including adequate renal, liver, and bone marrow function, as well as an **ECOG Performance Status** of 0 or 1. The trial population is characterized by their recent diagnosis of FIGO Stage III or IV disease and having undergone optimal debulking surgery. Lifestyle considerations such as diet and physical activity are not specified, but participants must be willing to complete quality of life questionnaires. The study does not include male subjects and involves a vulnerable population, given the nature of the disease. Key inclusion criteria also require participants to have suitable venous access and specific **CA 125 levels**. The trial does not provide additional information on lifestyle habits or other demographic details.

Plans and Procedures

The clinical trial is a **Phase 3**, double-blind, placebo-controlled, multicenter study designed to evaluate the efficacy of **chemo-immunotherapy** with Oregovomab in combination with Paclitaxel and Carboplatin compared to chemotherapy alone in patients with advanced epithelial ovarian, fallopian tube, or peritoneal carcinoma. The primary objective is to assess progression-free survival (PFS) using investigator assessment of scans according to RECIST v1.1. The trial is expected to conclude by August 2027, with recruitment having commenced in August 2020.

Participants will be randomly assigned to receive either the investigational treatment or a placebo, both administered intravenously. The study involves several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor treatment response and safety, and an end-of-study visit to assess final outcomes. The inclusion criteria require participants to be adults aged 18 or older with newly diagnosed FIGO Stage III or IV disease, who have undergone optimal debulking surgery. Participants must also meet specific renal, hepatic, and hematologic function criteria and agree to use effective contraception if of childbearing potential.

The expected duration of participant involvement is approximately 35 weeks, corresponding to the maximum treatment period. Participants may be withdrawn from the study early due to adverse events, non-compliance with the study protocol, or withdrawal of consent. The primary endpoint is the time from randomization to the first documented disease progression or death. Secondary endpoints include overall survival, incidence of adverse events, and changes in quality of life scores. The trial is not classified as low intervention, reflecting its comprehensive design and rigorous monitoring requirements.

Treatment

The clinical trial involves the administration of **Oregovomab**, a **solution for infusion**. Oregovomab is a biological product of protein origin, specifically classified as "Protein - Other." It is manufactured by OncoQuest Pharmaceuticals Inc. The pharmaceutical form of Oregovomab is a solution for infusion, and it is administered via the **intravenous route**. The dosing regimen for Oregovomab includes a maximum daily dose of 2 mg and a total maximum dose of 8 mg over a treatment period of 35 days. The product is identified by the sponsor product code MAB-B43.13 and has been designated as an orphan drug under the number EU/3/23/2857.

The trial also includes a **placebo** as a comparator treatment. The placebo is administered in the same pharmaceutical form and route as Oregovomab, ensuring blinding in this double-blind, placebo-controlled study. The placebo is used in conjunction with standard chemotherapy agents, **Paclitaxel** and **Carboplatin**, which are part of the chemo-immunotherapy regimen being evaluated. The study aims to compare the efficacy of the chemo-immunotherapy regimen (Paclitaxel-Carboplatin-Oregovomab) against the chemotherapy regimen (Paclitaxel-Carboplatin-Placebo) in patients with advanced epithelial ovarian, fallopian tube, or peritoneal carcinoma.

Efficacy

Efficacy in this clinical trial will be assessed primarily through **Progression-Free Survival (PFS)**, which is defined as the time from randomization following surgery to the first documented progression of disease or death from any cause, as determined by the investigator using RECIST v1.1 criteria. Secondary efficacy endpoints include **Overall Survival (OS)**, measured from the date of randomization to the date of death from any cause, and the incidence of adverse events, including serious adverse events, deaths, and adverse events leading to treatment discontinuation. Additionally, changes from baseline in the global health status/quality of life scale score of the Functional Assessment of Cancer Therapy-Ovary (FACT-O TOI) and three additional questions from the NFOSI-18 will be evaluated in each treatment group.

The trial involves a comparison between chemo-immunotherapy (Paclitaxel-Carboplatin-Oregovomab) and chemotherapy (Paclitaxel-Carboplatin-Placebo) in patients with advanced epithelial ovarian, fallopian tube, or peritoneal carcinoma. Efficacy assessments will be conducted at specified intervals throughout the study, with imaging and clinical evaluations performed according to the trial protocol. The trial is designed to provide comprehensive data on the efficacy of the investigational treatment regimen in improving progression-free survival and overall survival, as well as its impact on patient-reported outcomes related to quality of life.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Adults 18 years old or older
Subjects with newly diagnosed epithelial adenocarcinoma of ovarian, fallopian tube or peritoneal origin FIGO Stage III or IV disease.
Eligible histologic epithelial cell types: high grade serous adenocarcinoma, high grade endometrioid adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, or adenocarcinoma not otherwise specified (N.O.S.).
Completed debulking surgery (either primary debulking surgery or interval debulking surgery at the discretion of the investigator), as defined below: a. For subjects who undergo primary debulking surgery (Cohort 1 - Primary Surgery): i. Subject must receive initial dose of paclitaxel 175 mg/m2 given intravenously, and carboplatin AUC 6 IV every 3 weeks (21 days) for 6 cycles. Carboplatin total dose given as 5 consecutive daily pulse doses, for subjects who experiences significant grade 3 or higher emesis. Subsequent dose modifications will be instituted per protocol. Cycle 1 of chemotherapy ± oregovomab/placebo must be anticipated to occur within 6 weeks after primary debulking surgery, and ii. The primary debulking surgery is optimal, R1 or R0 (defined as R1, macroscopic less than 1 cm in diameter, or R0, microscopic or no evidence of tumor). Assessment of intra-abdominal optimal debulking will be determined at the time of the surgical procedure and not by postsurgical imaging (i.e., CT scan). Assessment of intra-abdominal optimal debulking will be determined at the time of the surgical procedure and not by post-surgical imaging (i.e., CT scan). b. For subjects who will undergo interval debulking surgery (IDS) (Cohort 2 – NACT+/Interval Surgery): i. Prior to IDS, subject must have received neoadjuvant treatment with 3cycles of paclitaxel and carboplatin a) paclitaxel must have been started at an initial dose of 175 mg/m2 given intravenously (IV) every 3 weeks (21 Days) ). If the subject experienced grade 3 or 4 adverse events with paclitaxel 175mg/m2, dose reduction to 135 mg/m2 is allowed for cycles 2 and/or 3. b) Carboplatin initial dose must have been an area under the curve (AUC) 5-6 IV approximately every 3 weeks (21 Days) ii. Once subjects are enrolled on the protocol, they must receive paclitaxel 175mg/m2 IV and carboplatin AUC 5-6 IV every 3 weeks starting cycle 4. Subsequent dose modifications will be instituted per protocol. Cycle 4 of chemotherapy ± oregovomab/placebo must be anticipated to occur within 6 weeks after interval debulking surgery, and iii. The interval debulking surgery is optimal, R1 or R0 (defined as R1, macroscopic less than 1 cm in diameter, or R0, microscopic or no evidence of tumor). Assessment of optimal debulking of intra-abdominal disease will be determined at the time of the surgical procedure and not by post-surgical imaging (i.e., CT scan).
Suitable venous access for the study-required procedures.
CA 125 levels: a) Cohort 1 – Primary Surgery: Preoperative serum CA-125 levels ≥ 50 U/mL, or b) Cohort 2 – NACT + Interval Surgery: serum CA-125 levels ≥ 50 U/mL prior to first neoadjuvant chemotherapy.
Adequate bone marrow function: a. Absolute neutrophil count (ANC) ≥ 1,500/μL b. Platelets ≥ 100,000/μL
Hemoglobin ≥ 8.0 g/dL (Note: Blood transfusion is permitted up to 48 hours before first dose of study treatment).
Adequate liver function: a. Bilirubin < 1.5 times upper limit of normal (ULN) b. Lactate Dehydrogenase (LDH), SGOT/AST and SGPT/ALT < 2.5 times ULN
Adequate renal function: a. Creatinine ≤ 1.5 times ULN
ECOG Performance Status of 0 or 1
For women of childbearing potential, must be willing to avoid pregnancy by using a highly effective method of contraception from the first dose of study treatment to 6 months after last dose of study treatment. Adequate contraception is defined in Section 8.2.5. (Belgium and South Korea Only: Use of a highly effective method of contraception from 28 days before first dose).
Signed informed consent and authorization permitting release of personal health information.
Willingness and ability to complete patient quality of life questionnaires.

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Exclusion Criteria

BRCA1 or BRCA2 germline gene mutation test result with: a. Pathogenic, ambiguous or inconclusive result available within 28 days prior to starting study treatment. Subjects with BRCA1 or BRCA2 variants of uncertain significance can enroll onto the study as long as there is no intent to administer PARP inhibitors for front-line maintenance therapy, or b. Known BRCA1 and BRCA2 somatic mutations, if testing is performed
Known Somatic Homologous Recombination Deficiency (HRD) who will receive PARP inhibitor front-line maintenance therapy. Subjects with somatic HRD are eligible as long as there is no intent to administer PARP inhibitor front-line maintenance therapy.
Subjects with mucinous adenocarcinoma, carcinosarcoma, tumors with neuroendocrine features and low-grade adenocarcinoma.
Female subjects who are lactating and breastfeeding, orbreastfeeding or have a positive serum pregnancy test within 7 days prior to the first dose of study treatment (C1D1 for Cohort 1 or C4D1 for Cohort 2).
Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
Active autoimmune disease, such as rheumatoid arthritis, SLE, ulcerative colitis, Crohn's Disease, MS, or ankylosing spondylitis requiring active disease modifying treatment.
Known allergy to murine proteins or hypersensitivity to any of the excipients of the oregovomab, paclitaxel, or carboplatin.
Chronically treated with immunosuppressive drugs such as cyclosporine, adrenocorticotropic hormone (ACTH), etc.
Chronic therapeutic corticosteroid use, defined as > 5 days of prednisone or equivalent, with the exception of inhalers or those on a pre-planned steroid taper. (Note: Premedication with corticosteroids per institutional standard of care is allowed.)
Recognized acquired, hereditary, or congenital immunodeficiency disease, including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia.
Clinically significant active infection(s) at the time of screening.
Any of the following conditions (on-study testing is not required unless it is required by a specific participating country): a. Known HIV-infected subjects unless on effective anti-retroviral therapy with an undetectable viral load within 6 months, or b. Known or suspected hepatitis B if active infection (subjects with chronic hepatitis B infection must have an undetectable HBV viral load on suppressive therapy, if indicated; positive surface antibody alone is not an exclusion), or c. Known or suspected hepatitis C infection which has not been treated and cured unless currently on treatment with an undetectable viral load).
Uncontrolled or life-threatening diseases compromising safety evaluation.
Diagnosed or treated for another malignancy within 5 years before the first dose, or previously diagnosed with another malignancy and have any evidence of residual disease, including ductal carcinoma in situ of the breast. Subjects with non-melanoma skin cancer, other carcinoma in situ if have undergone complete resection or cervix carcinoma in situ are not excluded if they have undergone complete resection. Synchronous endometrial and prior diagnosis of endometrial cancer within 5 years is not excluded if all of the following conditions are met: Stage IA, superficial myometrial invasion, without lymphovascular invasion, and not poorly differentiated subtypes including papillary serous, clear cell lesions.
Contraindications to the use of pressor agents.
Undergone more than one surgical debulking or have not recovered from surgery.
Anticipated treatment with any other anti-cancer medications, including bevacizumab, PARP inhibitors, or any investigational agent(s) during the study.
History or evidence upon physical examination of CNS disease, seizures not controlled with standard medical therapy, or any brain metastases.
Any of the following cardiovascular conditions: a. Acute myocardial infarction within 6 months before the first dose of study treatment. b. Current history of New York Heart Association (NYHA) Class III or IV heart failure (see Appendix H). c. Evidence of current uncontrolled cardiovascular conditions including cardiac arrhythmias, angina, pulmonary hypertension, or electrocardiographic clinically significant findings
Unable to read or understand or unable to sign the necessary written consent before starting treatment.
May not receive any live, attenuated vaccine administered within 28 days (or 4 weeks) prior to enrolment, during the study, and for at least 90 days after the last dose of study treatment.
Subjects who receive Hyperthermic Intraperitoneal Chemotherapy (HIPEC), any other anti-cancer medications, including bevacizumab, PARP inhibitors, or any other investigational agent(s) with 3 cycles of paclitaxel and carboplatin neo-adjuvant treatment prior to IDS will be excluded.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Belgium	Not Recruiting	16 Aug 2020	6
Czechia	Not Recruiting	16 Aug 2020	26
Hungary	Not Recruiting	16 Aug 2020	10
Italy	Not Recruiting	16 Aug 2020	9
Spain	Not Recruiting	16 Aug 2020	13