A Phase II Study Evaluating the Effect of GEN-1 on SLL When Administered in Combination With Bevacizumab and NACT in Subjects Newly Diagnosed With Advanced Ovarian, Fallopian Tube or Primary Peritoneal Cancer (MRD)

• ClinicalTrials.gov Identifier: NCT05739981
• Recruitment Status: Recruiting
• First Posted: February 22, 2023
• Last Update Posted: February 22, 2023
• Sponsor: Imunon
• Collaborator: Break Through Cancer Foundation
• Information provided by (Responsible Party): Imunon

Study Description

Brief Summary:

This is a 1:1 randomized, open label, multi-center phase II trial to evaluate the safety, dosing, efficacy, and biological activity of adding GEN-1 to chemotherapy + BEV compared to chemotherapy + BEV alone.

Condition or disease	Intervention/treatment	Phase
Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer	Drug: Paclitaxel; Drug: Carboplatin; Drug: Bevacizumab; Drug: GEN1	Phase 2

Detailed Description:

This is a 1:1 randomized, open label, multi-center phase II trial to evaluate the safety, dosing, efficacy, and biological activity of adding GEN-1 to chemotherapy + BEV compared to chemotherapy + BEV alone. The chemotherapy (NACT & adjuvant) will be a standard regimen of carboplatin + paclitaxel administered every three weeks for a total of 7-9 cycles. The protocol requires at least 4 cycles of NACT and allows up to 2 additional cycles of neoadjuvant therapy at the Principal Investigator's discretion based on response and other clinical considerations. ICS will take place after 3-4 weeks from last dose of NACT. Following at least a 4-week recovery from ICS, 3 additional adjuvant cycles of study treatments will be administered. The minimum time interval between surgery and BEV administration will be 4 weeks for safety. BEV will be included at Cycles 2, 3, 6, and 7. BEV may be substituted by an FDA approved biosimilar. In the experimental arm, GEN-1 will begin on C1D15 and continue weekly though the last cycle of adjuvant therapy. The experimental arm will add GEN-1 weekly to each cycle of chemotherapy + BEV beginning with cycle 1 day 15.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study Evaluating the Effect of GEN-1 (IL-12 Plasmid Formulated With PEG-PEI-Cholesterol Lipopolymer) on Second Look Laparoscopy (SLL) When Administered in Combination With Bevacizumab (BEV) and Neoadjuvant Chemotherapy (NACT) in Subjects Newly Diagnosed With Advanced Ovarian, Fallopian Tube or Primary Peritoneal Cancer
• Actual Study Start Date: February 10, 2023
• Estimated Primary Completion Date: August 30, 2026
• Estimated Study Completion Date: January 30, 2028

Arms and Interventions

Arm	Intervention/treatment
Experimental: Chemotherapy + BEV + GEN-1 (Experimental); Chemotherapy (neoadjuvant and adjuvant): Paclitaxel 175 mg/m2 IV followed by carboplatin AUC 5-6 IV starting on C1D1. During the neoadjuvant period, there will be a total of 4 - 6 cycles, at the Investigator's discretion, repeated every 21 days. Adjuvant chemotherapy for another 3 cycles. BEV 15 mg/kg IV administration will be on Day 1 of Cycles 2, 3, 6, and 7. During the maintenance phase, BEV 15 mg/kg will be administered every 3 weeks as a single agent until disease progression or unacceptable toxicity for an additional 18 cycles. In total, BEV may be administered up to 22 cycles. FDA approved BEV biosimilars may be used in this study in place of BEV. In addition to the standard drug regimen of the control arm, GEN-1 80 mg/m2 IP will be administered weekly beginning C1D15. At the conclusion of chemotherapy, GEN-1 will be administered every 21 days with BEV in subjects who are BRCA-/HRP until disease progression or unacceptable toxicity for up to an additional 18 cycles.	Drug: Paclitaxel; Paclitaxel 175 mg/m2 IV; Drug: Carboplatin; Carboplatin AUC 5-6 IV; Drug: Bevacizumab; BEV 15 mg/kg IV administration will be on Day 1 of Cycles 2, 3, 6, and 7. During the maintenance phase, BEV 15 mg/kg will be administered every 3 weeks as a single agent until disease progression or unacceptable toxicity for an additional 18 cycles. In total, BEV may be administered up to 22 cycles. FDA approved BEV biosimilars may be used in this study in place of BEV.; Drug: GEN1; IL-12 Plasmid Formulated with PEG-PEI-Cholesterol Lipopolymer
Chemotherapy + BEV (Control); Chemotherapy (neoadjuvant and adjuvant): Paclitaxel 175 mg/m2 IV followed by carboplatin AUC 5-6 IV starting on C1D1. During the neoadjuvant period, there will be a total of 4 - 6 cycles, at the Investigator's discretion, repeated every 21 days. Adjuvant chemotherapy for another 3 cycles. BEV 15 mg/kg IV administration will be on Day 1 of Cycles 2, 3, 6, and 7. During the maintenance phase, BEV 15 mg/kg will be administered every 3 weeks as a single agent until disease progression or unacceptable toxicity for an additional 18 cycles. In total, BEV may be administered up to 22 cycles. FDA approved BEV biosimilars may be used in this study in place of BEV.	Drug: Paclitaxel; Paclitaxel 175 mg/m2 IV; Drug: Carboplatin; Carboplatin AUC 5-6 IV; Drug: Bevacizumab; BEV 15 mg/kg IV administration will be on Day 1 of Cycles 2, 3, 6, and 7. During the maintenance phase, BEV 15 mg/kg will be administered every 3 weeks as a single agent until disease progression or unacceptable toxicity for an additional 18 cycles. In total, BEV may be administered up to 22 cycles. FDA approved BEV biosimilars may be used in this study in place of BEV.

Outcome Measures

Primary Outcome Measures :

1. Minimal Residual Disease [ Time Frame: 8 months ]
   To determine if the addition of GEN-1 can reduce rate of MRD at SLL from an expected 70% in the control group (chemotherapy + BEV) to 35% in the experimental group (chemotherapy + BEV + GEN-1).

Secondary Outcome Measures :

1. PFS [ Time Frame: 2 years ]
   Progression Free Survival comparison in experimental vs. control arm
2. OS [ Time Frame: 3 years ]
   Overall Survival comparison in experimental vs. control arm

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Subjects must have a suspected diagnosis of high grade epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with histologic confirmation per pre- treatment biopsies.
2. Subjects must have an International Federation of Gynecology and Obstetrics (FIGO) stage of III or IV who based on standard of care clinical considerations have been determined to benefit from neoadjuvant therapy.
3. Subjects only with high grade serous adenocarcinoma histologic epithelial cell type are eligible.
4. Subjects must have adequate: bone marrow function, renal function, hepatic function, and neurologic function.
5. Subjects should be free of active infection requiring isolation, parenteral antibiotics or a serious uncontrolled medical illness or disorder within four weeks of study entry.
6. Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to the first treatment. Continuation of hormone replacement therapy is permitted.
7. Subjects must have a performance status score of 0-1 by Eastern Cooperative Group (ECOG) criteria.
8. Subjects of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of protocol therapy and be practicing an effective form of contraception.
9. Subjects must have satisfactory results for the baseline laboratory analyses and diagnostic procedures as specified in the protocol.
10. Subjects must have signed an IRB-approved informed consent and authorization permitting release of personal health information.

Exclusion Criteria:

1. Subjects who have received prior treatment with GEN-1 or who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to GEN-1 or other drugs used in this study.
2. Subjects who have received oral or parenteral corticosteroids within 2 weeks of study entry or who have a clinical requirement for ongoing systemic immunosuppressive therapy such as chronic steroid use not related to chemotherapy administration.
3. Subjects with autoimmune disease requiring immunosuppressive therapy within the last 2 years.
4. Subjects with known human immunodeficiency virus (HIV) or human T-lymphotropic virus (HTLV) infections are excluded.
5. Subjects with other invasive malignancies are excluded if there is any evidence of the invasive malignancy being present within the last three years. Subjects are also excluded if their previous cancer treatment contraindicates this protocol therapy.
6. Subjects who have received prior radiotherapy or chemotherapy to any portion of the abdominal cavity or pelvis are excluded.
7. Subjects with known active hepatitis.
8. Subjects with nephrotic syndrome.
9. Subjects with concurrent severe medical problems unrelated to the malignancy that would significantly limit full compliance with the study or expose the patient subject to extreme risk or decreased life expectancy.
10. Subjects with clinically significant cardiovascular disease.
11. Subjects of childbearing potential, not practicing adequate contraception, subjects who are pregnant, or subjects who are breastfeeding are not eligible for this trial.
12. Subjects with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study.
13. Subjects with a history of diverticulitis.
14. Subjects having hemoptysis within the last month.
15. Subjects with any condition/anomaly that would interfere with the appropriate placement of the IP catheter for study drug administration including abdominal surgery within 4 weeks of study entry (for reasons other than IP port placement), intestinal dysfunction, fistulas, or suspected extensive adhesions from prior history or finding at laparoscopy.

Contacts and Locations

Contacts

Contact: Khursheed Anwer, PhD; 609.896.9100; kanwer@imunon.com

Contact: Lauren Musso; 609.896.9100; lmusso@imunon.com

Locations

United States, Texas

University of Texas MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Contact: Kerri Fernandes kefernan@mdanderson.org

Principal Investigator: Amir Jazaeri, MD

Sponsors and Collaborators

Imunon

Break Through Cancer Foundation

Investigators

• Study Chair: Amir Jazaeri, MD; University of Texas MD Anderson Center

More Information

• Responsible Party: Imunon
• ClinicalTrials.gov Identifier: NCT05739981
• Other Study ID Numbers: 201-21-202
• First Posted: February 22, 2023
• Last Update Posted: February 22, 2023
• Last Verified: February 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Fallopian Tube Neoplasms; Peritoneal Neoplasms; Neoplasms by Site; Neoplasms; Adnexal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Fallopian Tube Diseases; Abdominal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases; Paclitaxel; Bevacizumab; Carboplatin; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors