A Study of Intraperitoneally Administered AVB-001 in Patients With Serous Adenocarcinoma of the Ovary

NCT05538624 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: AVB-1A-101
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 5

Brief Summary

This is an open-label, First-in-Human, Phase 1/2, multicenter study to evaluate the safety and efficacy of a single dose of AVB-001. AVB-001 is an encapsulated cell product engineered to produce native human interleukin-2 (hIL-2). It is delivered intraperitoneally (IP) to patients with high grade serous adenocarcinoma of the ovary, primary peritoneum, or fallopian tube.

Conditions

Neoplasm, Ovarian; Fallopian Tube Cancer; Primary Peritoneal Cavity Cancer; Adenocarcinoma Ovary; Serous Adenocarcinoma of Ovary; Serous Adenocarcinoma of Primary Peritoneum; Primary Peritoneal Carcinoma; High Grade Serous Adenocarcinoma

Keywords

Ovarian Cancer; Primary Peritoneum Cancer; Fallopian Tube Cancer; Immunotherapy; IL-2 Immunotherapy; Metastatic Cancer; Human Interleukin 2; Interleukin 2; IL-2; Encapsulated Cell Therapy

Outcome Measures

Primary Outcomes (3)

• Incidence of dose limiting toxicities (DLTs) of IP administered AVB-001 to determine the MTD and RP2D in the Dose Escalation Phase (Part 1)

  4 weeks

• Incidence of treatment-emergent adverse events (AEs) and serious AEs (SAEs) of IP administered AVB-001 in the Dose Escalation Phase (Part 1)

  1 year

• Investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 of IP administered AVB-001 in the Dose Expansion Phase (Part 2)

  1 year

Secondary Outcomes (12)

• Investigator-assessed ORR per RECIST v1.1 of IP administered AVB-001 in the Dose Escalation Phase (Part 1)

  1 year

• Investigator-assessed ORR per the modified RECIST guideline for immunotherapy (iRECIST) of IP administered AVB-001 in the Dose Escalation Phase (Part 1)

  1 year

• Duration of response (DOR) in the Dose Escalation Phase (Part 1)

  1 year

• Progression Free Survival (PFS) in the Dose Escalation Phase (Part 1)

  1 year

• Overall survival (OS) in the Dose Escalation Phase (Part 1)

  1 year

Other Outcomes (2)

• Immunologic changes in peripheral blood and IP environments in the Dose Escalation and Dose Expansion Phases (Parts 1 and 2)

  1 year (Part 1); 1 year (Part 2)

• Analysis of anti-drug antibodies (ADA) to AVB-001 in human serum in the Dose Escalation and Dose Expansion Phases (Parts 1 and 2)

  1 year (Part 1); 1 year (Part 2)

Study Arms (1)

Part 1 escalating AVB-001 between 0.6 and 3.6 ug hIL-2/kg/day; and Part 2 AVB-001 at the MTD/RP2D

EXPERIMENTAL

Part 1: one of four ascending doses of AVB-001 planned for IP, single dose administration at each dose level cohort of the Dose Escalation Phase. Part 2: a single dose of AVB-001 at the MTD/RP2D level (determined in Part 1) to be further evaluated in the Dose Expansion Phase.

Drug: AVB-001 (Dose Escalation Phase); Drug: AVB-001 (Dose Expansion Phase)

Interventions

AVB-001 (Dose Escalation Phase) DRUG

One of four ascending doses of AVB-001 planned for IP, single dose administration in each dose level cohort of the Dose Escalation Phase (Part 1).

Part 1 escalating AVB-001 between 0.6 and 3.6 ug hIL-2/kg/day; and Part 2 AVB-001 at the MTD/RP2D

AVB-001 (Dose Expansion Phase) DRUG

The MTD/RP2D as determined in the Dose Escalation Phase will be further evaluated in the Dose Expansion Phase.

Part 1 escalating AVB-001 between 0.6 and 3.6 ug hIL-2/kg/day; and Part 2 AVB-001 at the MTD/RP2D

Eligibility Criteria

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

You may qualify if:

• Have histologically confirmed, metastatic or unresectable, platinum-resistant, high-grade, serous adenocarcinoma of the ovary, primary peritoneum, or fallopian tube;
• Note: For the purposes of this study, platinum-resistant is defined as a patient who has received platinum-containing chemotherapy and either has platinum-refractory disease (progressed during initial platinum-based chemotherapy) or resistant disease (relapsed within 6 months of initial platinum-containing chemotherapy) or, if previously with platinum-sensitive disease, has received at least 2 lines of platinum-containing chemotherapy and progressed.
• Note: A pathology report confirming histology will be required for enrollment.
• Have not received more than 5 lines of prior therapy;
• May have received poly adenosine diphosphate-ribose polymerase (PARP) inhibitors, bevacizumab (or any other antiangiogenic agent), immunotherapy, or cell therapies. (Patients with germline or somatic breast cancer gene (BRCA) mutations must have progressed or been intolerant to PARP inhibitor therapy);
• Have an Eastern Cooperative Oncology Group performance status 0 to 1 at Screening;
• Meet the following laboratory criteria:
• Absolute neutrophil count \>1500/μl;
• Hemoglobin level ≥9.0 g/dL (transfusion allowed);
• Platelet count ≥100,000/μl;
• Creatinine clearance ≥50 mL/minute, measured using the Cockcroft-Gault formula, and serum creatinine ≤1.5 upper limit of normal (ULN);
• Alanine aminotransferase (ALT) ≤2.5× ULN, aspartate aminotransferase (AST) ≤2.5×ULN; and total bilirubin ≤1.5×ULN (or ≤3×ULN in cases of Gilbert's syndrome); and
• International normalized ratio \<1.5 and activated partial thromboplastin time (or partial thromboplastin time) within normal limits per the institution.
• Note: Patients on direct-acting anticoagulants or other anticoagulation medications are eligible as long as they are able to hold the drug for the laparoscopic procedure on Day 1 per institutional guidance.
• Have evidence of measurable disease on computed tomography (CT) or magnetic resonance imaging (MRI) scan as defined by RECIST v1.1;

You may not qualify if:

• Have low-grade serous, mucinous, clear cell, or endometrioid adenocarcinoma of the ovary, primary peritoneum, or fallopian tube; carcinosarcoma; or a mixed histology tumor;
• Have another malignancy or have had a prior malignancy within 3 years prior to the first dose of study drug or any evidence of residual disease from a previously diagnosed malignancy, excluding adequately managed with curative-intent treatment for basal cell carcinoma, squamous cell carcinoma of the skin, cervical intraepithelial neoplasia, cervical carcinoma in situ, melanoma in situ, or ductal carcinoma in situ of the breast;
• Have a known or suspected allergy to AVB-001 or known or suspected allergy to any components of AVB-001, including alginate or seaweed;
• Have any condition that, in the opinion of the Investigator, would lead to the inability of the patient to comply with the Protocol.

Sponsors & Collaborators

• Avenge Bio, Inc: lead

Study Sites (5)

National Cancer Institute

Bethesda, Maryland, 20892, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

UPMC Magee-Womens Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

Women & Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Not applicable in this open-label trial.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In this two-part study, Part 1 is the Dose Escalation Phase; Part 2 is the Dose Expansion Phase.

Study Record Dates

• First Submitted: August 22, 2022
• First Posted: September 14, 2022
• Study Start: December 9, 2022
• Primary Completion: April 1, 2024
• Study Completion: April 10, 2024
• Last Updated: April 24, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)