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

Primary Purpose

Neoplasm, Ovarian, Fallopian Tube Cancer, Primary Peritoneal Cavity Cancer

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AVB-001 (Dose Escalation Phase)
AVB-001 (Dose Expansion Phase)
Sponsored by
Avenge Bio, Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neoplasm, Ovarian focused on measuring Ovarian Cancer, Primary Peritoneum Cancer, Fallopian Tube Cancer, Immunotherapy, IL-2 Immunotherapy, Metastatic Cancer, Human Interleukin 2, Interleukin 2, IL-2, Encapsulated Cell Therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. 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.

  2. Have not received more than 5 lines of prior therapy;
  3. 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);
  4. Have an Eastern Cooperative Oncology Group performance status 0 to 1 at Screening;
  5. 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.

  6. Have evidence of measurable disease on computed tomography (CT) or magnetic resonance imaging (MRI) scan as defined by RECIST v1.1;

    Note: Measurable disease cannot include a lesion that was biopsied. Patients must, at a minimum, have 1 measurable lesion.

    Note: Patients with IP disease who also have disease involving the pleural cavity or distant metastases will be eligible if they have measurable or evaluable disease in the IP cavity.

  7. Are willing and able to provide written informed consent or have a legally authorized representative willing and able to provide informed consent at Screening.

Exclusion Criteria:

  1. Have low-grade serous, mucinous, clear cell, or endometrioid adenocarcinoma of the ovary, primary peritoneum, or fallopian tube; carcinosarcoma; or a mixed histology tumor;
  2. 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;
  3. Have a known or suspected allergy to AVB-001 or known or suspected allergy to any components of AVB-001, including alginate or seaweed;
  4. Have any condition that, in the opinion of the Investigator, would lead to the inability of the patient to comply with the Protocol.

Sites / Locations

  • National Cancer InstituteRecruiting
  • Massachusetts General HospitalRecruiting
  • UPMC Magee-Womens HospitalRecruiting
  • Women & Infants Hospital of Rhode IslandRecruiting
  • MD Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

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

Arm Description

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.

Outcomes

Primary Outcome Measures

Incidence of dose limiting toxicities (DLTs) of IP administered AVB-001 to determine the MTD and RP2D in the Dose Escalation Phase (Part 1)
Incidence of treatment-emergent adverse events (AEs) and serious AEs (SAEs) of IP administered AVB-001 in the Dose Escalation Phase (Part 1)
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)

Secondary Outcome Measures

Investigator-assessed ORR per RECIST v1.1 of IP administered AVB-001 in the Dose Escalation Phase (Part 1)
Investigator-assessed ORR per the modified RECIST guideline for immunotherapy (iRECIST) of IP administered AVB-001 in the Dose Escalation Phase (Part 1)
Duration of response (DOR) in the Dose Escalation Phase (Part 1)
Progression Free Survival (PFS) in the Dose Escalation Phase (Part 1)
Overall survival (OS) in the Dose Escalation Phase (Part 1)
Concentrations of hIL-2 in blood and ascites/IP fluid during the Dose Escalation Phase (Part 1)
Incidence of treatment-emergent AEs and SAEs of IP administered AVB-001 in the Dose Expansion Phase (Part 2)
Investigator-assessed ORR per iRECIST of IP administered AVB-001 in the Dose Expansion Phase (Part 2)
DOR in the Dose Expansion Phase (Part 2)
PFS in the Dose Expansion Phase (Part 2)
OS in the Dose Expansion Phase (Part 2)
Concentrations of hIL-2 in blood and ascites/IP fluid during the Dose Expansion Phase (Part 2)

Full Information

First Posted
August 22, 2022
Last Updated
October 11, 2023
Sponsor
Avenge Bio, Inc
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1. Study Identification

Unique Protocol Identification Number
NCT05538624
Brief Title
A Study of Intraperitoneally Administered AVB-001 in Patients With Serous Adenocarcinoma of the Ovary
Official Title
A Phase 1/2 Open-Label, Multicenter, Dose Escalation and Expansion Study of AVB-001, an Intraperitoneally Administered, Cell-Generated, Human IL-2 Immunotherapy in Patients With Platinum-Resistant, High-Grade, Serous Adenocarcinoma of the Ovary, Primary Peritoneum, or Fallopian Tube
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 9, 2022 (Actual)
Primary Completion Date
August 2026 (Anticipated)
Study Completion Date
August 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Avenge Bio, Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
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 (IL-2). It is delivered intraperitoneally (IP) to patients with high grade serous adenocarcinoma of the ovary, primary peritoneum, or fallopian tube. The study will be conducted in two parts. Part 1 is the Dose Escalation Phase using a Bayesian optimal interval (BOIN) model-assisted design in which a single dose of 1 of 4 dose levels of AVB-001 will be administered intraperitoneally (IP) in up to 24 patients. The four ascending dose levels of AVB-001 are targeted to produce hIL-2 levels of 0.6, 1.2, 2.4, and 3.6 μg hIL-2/kg/day. The purpose of Part 1 is to determine the maximally tolerated dose (MTD)/recommended Phase 2 dose (RP2D) level. Part 2 is the Dose Expansion Phase 2 in which a single dose of AVB-001 at the RP2D will be administered in up to 20 additional adult patients with platinum-resistant, high-grade, serous adenocarcinoma of the ovary, primary peritoneum, or fallopian tube. Additional expansion cohorts may be opened in Part 2 either as monotherapy or as an exploratory combination strategy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
In this two-part study, Part 1 is the Dose Escalation Phase; Part 2 is the Dose Expansion Phase.
Masking
None (Open Label)
Masking Description
Not applicable in this open-label trial.
Allocation
N/A
Enrollment
44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
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
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
AVB-001 (Dose Escalation Phase)
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
AVB-001 (Dose Expansion Phase)
Intervention Description
The MTD/RP2D as determined in the Dose Escalation Phase will be further evaluated in the Dose Expansion Phase.
Primary Outcome Measure Information:
Title
Incidence of dose limiting toxicities (DLTs) of IP administered AVB-001 to determine the MTD and RP2D in the Dose Escalation Phase (Part 1)
Time Frame
4 weeks
Title
Incidence of treatment-emergent adverse events (AEs) and serious AEs (SAEs) of IP administered AVB-001 in the Dose Escalation Phase (Part 1)
Time Frame
1 year
Title
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)
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Investigator-assessed ORR per RECIST v1.1 of IP administered AVB-001 in the Dose Escalation Phase (Part 1)
Time Frame
1 year
Title
Investigator-assessed ORR per the modified RECIST guideline for immunotherapy (iRECIST) of IP administered AVB-001 in the Dose Escalation Phase (Part 1)
Time Frame
1 year
Title
Duration of response (DOR) in the Dose Escalation Phase (Part 1)
Time Frame
1 year
Title
Progression Free Survival (PFS) in the Dose Escalation Phase (Part 1)
Time Frame
1 year
Title
Overall survival (OS) in the Dose Escalation Phase (Part 1)
Time Frame
1 year
Title
Concentrations of hIL-2 in blood and ascites/IP fluid during the Dose Escalation Phase (Part 1)
Time Frame
1 year
Title
Incidence of treatment-emergent AEs and SAEs of IP administered AVB-001 in the Dose Expansion Phase (Part 2)
Time Frame
1 year
Title
Investigator-assessed ORR per iRECIST of IP administered AVB-001 in the Dose Expansion Phase (Part 2)
Time Frame
1 year
Title
DOR in the Dose Expansion Phase (Part 2)
Time Frame
1 year
Title
PFS in the Dose Expansion Phase (Part 2)
Time Frame
1 year
Title
OS in the Dose Expansion Phase (Part 2)
Time Frame
1 year
Title
Concentrations of hIL-2 in blood and ascites/IP fluid during the Dose Expansion Phase (Part 2)
Time Frame
1 year
Other Pre-specified Outcome Measures:
Title
Immunologic changes in peripheral blood and IP environments in the Dose Escalation and Dose Expansion Phases (Parts 1 and 2)
Time Frame
1 year (Part 1); 1 year (Part 2)
Title
Analysis of anti-drug antibodies (ADA) to AVB-001 in human serum in the Dose Escalation and Dose Expansion Phases (Parts 1 and 2)
Time Frame
1 year (Part 1); 1 year (Part 2)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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; Note: Measurable disease cannot include a lesion that was biopsied. Patients must, at a minimum, have 1 measurable lesion. Note: Patients with IP disease who also have disease involving the pleural cavity or distant metastases will be eligible if they have measurable or evaluable disease in the IP cavity. Are willing and able to provide written informed consent or have a legally authorized representative willing and able to provide informed consent at Screening. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Claudio Dansky Ullmann, MD
Phone
508-290-0502
Email
info@avengebio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claudio Dansky Ullmann, MD
Organizational Affiliation
Avenge Bio, Inc
Official's Role
Study Director
Facility Information:
Facility Name
National Cancer Institute
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stephanie Canady, RN
Phone
240-858-7573
Email
stephanie.canady@nih.gov
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Oladapo Yeku, MD, PhD, FACP
Phone
617-724-4000
Email
oyeku@mgh.harvard.edu
Facility Name
UPMC Magee-Womens Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joshua Plassmeyer, MSCR
Phone
412-648-6417
Email
plassmeyerjm@upmc.edu
Facility Name
Women & Infants Hospital of Rhode Island
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emma Locke
Phone
401-430-8181
Email
oncologyresearch@wihri.org
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shannon Westin, MD, MPH
Phone
713-794-4314
Email
swestin@mdanderson.org

12. IPD Sharing Statement

Plan to Share IPD
No

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

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