A Study of Navicixizumab Monotherapy or in Combination in Patients With Select Advanced Solid Tumors

A Phase 2, Multicenter, Open-Label Basket Study of Navicixizumab Monotherapy or in Combination With Paclitaxel or Irinotecan in Patients With Select Advanced Solid Tumors

This is a study of navicixizumab monotherapy or in combination with paclitaxel or irinotecan in patients with advanced cancer. Patients will be enrolled into one of the following cancer cohorts:

• Cohort A: CRC
• Cohort B: Gastric and GEJ cancer
• Cohort C: TNBC
• Cohort D: Platinum-resistant/refractory epithelial ovarian, primary peritoneal, or fallopian tube cancer (ovarian cancer)

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Colorectal Cancer; Ovarian Cancer; Triple Negative Breast Cancer
• Intervention / Treatment: Biological: navicixizumab+paclitaxel; Biological: navicixizumab+irinotecan; Biological: navicixizumab monotherapy

Detailed Description

After completing all screening procedures, including the submission of a tissue sample, patients that meet eligibility requirements will be assigned to receive navicixizumab alone or in combination with another anticancer agent. Treatment is assigned based on the patients type of tumor and the cohort that is open at the time of enrollment. Patients will receive treatment in 4 week cycles, attend study visits and have their heart monitored through echocardiograms and daily blood pressure measurements. Patients will also have their tumors monitored regularly through CT scans. Patients receiving benefit may continue on study drug until their tumor progresses, they experience intolerable side effects, their physician decides it is in their best interest to discontinue therapy or they choose to withdrawal from the study. After discontinuing study treatments, all patients will receive regular follow up calls or visits to assess their status and other anticancer treatments they may start.

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: OncXerna Therapeutics; Phone Number: 781-907-7810; Email: medical@oncxerna.com

Study Locations

• United States
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Recruiting
      • Genesis Cancer Center
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • Keck Medicine of USC
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Northside Hospital
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Recruiting
      • Hematology Oncology Clinic
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • New York University - Langone Health - Perlmutter Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43219
      • Recruiting
      • The Zangmeister Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient provides informed consent.
2. Patient is ≥18 years old.

3. Patient has one of the following locally advanced or metastatic, unresectable solid malignancies that is incurable:

   • CRC
   • Gastric or GEJ cancer
   • TNBC
   • Platinum-resistant/refractory epithelial ovarian, primary peritoneal, or fallopian tube cancer
4. Patient has provided an FFPE archive or newly obtained core or excisional biopsy of a tumor lesion.
5. Patient has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
6. Patient has measurable disease, as defined by RECIST v1.1.
7. Patient has adequate organ function.
8. Female patients of childbearing potential must have a negative pregnancy test.
9. Female patients of childbearing potential must agree to follow instructions for highly effective method(s) of contraception while receiving study treatment and for 6 months after the last dose of study drug.
10. Male patients with female sexual partners of childbearing potential must agree to use an acceptable form of contraception while receiving study treatment and for 6 months after the last dose of any study drug.
11. Patient is willing and able to comply with scheduled visits and procedures.

12. Patient must have discontinued other anticancer interventions before Cycle 1 Day 1 per study protocol.

    Cohort A1 and Cohort A2 - CRC only:

13. Patient has definitive pathologically confirmed adenocarcinoma of the colon or rectum.

14. Patient must have received at least 2 and no more than 3 prior lines of standard therapy for metastatic disease.

    Cohort B1 - Gastric/GEJ cancer only:

15. Patient has definitive pathologically confirmed metastatic gastric or GEJ adenocarcinoma that is not amenable to surgery.

16. Patient must have received only 1 prior line of standard therapy for metastatic disease.

    Cohort C1 and Cohort C2 - TNBC only:

17. Patient has definitive pathologically confirmed metastatic or locally advanced TNBC that is not amenable to surgery or radiotherapy with curative intent.

18. Patient must have received at least 2 prior and no more than 4 prior lines of standard therapy for metastatic disease.

    Cohort D1 - Ovarian cancer only:

19. Patient has definitive pathologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal cancer.
20. Patient must be considered platinum-resistant/refractory.
21. Patient must have received at least 2 and no more than 5 prior lines of standard therapy.

Exclusion Criteria:

1. Patient has cardiac conditions as listed in the protocol.
2. Patient has blood pressure (BP) >140/90 mmHg.
3. Patient is pregnant or lactating.
4. Patient has known untreated, active or uncontrolled brain metastases.
5. Patient with leptomeningeal disease.
6. Patient has a known additional malignancy that was progressing or required active treatment within 2 years prior to the first dose of study medication.
7. Patient has a history of bowel obstruction, including sub-occlusive disease, related to the underlying disease or history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess.
8. Patient has an active infection requiring IV systemic therapy.
9. Patient has known hypersensitivity to any components of any study drug or any of its excipients that, in the opinion of the investigator, suggests a high risk for a severe hypersensitivity reaction while on treatment.
10. Patient has a known clinically significant bleeding disorder.
11. Patient is currently using oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes for which the dose has not been stable for >14 days prior to C1D1.
12. Patient had hemoptysis >2.5 mL within 8 weeks prior to C1D1 or serious bleeding from another site within this time frame.
13. Patient had a major surgical procedure, or significant traumatic injury within 28 days prior to C1D1.
14. Patient has an uncontrolled seizure disorder or active neurologic disease.
15. Patient has a cardiac aneurysm.
16. Patient has a known psychiatric disorder, substance abuse disorder, or geographical travel limitations that in the opinion of the investigator would interfere with patient's ability to cooperate with the requirements of the study.

17. Patient has a history or current evidence of any condition, therapy, or laboratory abnormality that may confound the results of the study, interfere with the patient's participation for the full duration of the study, or indicates a condition for which study participation is not in the best interest of the patient, in the opinion of the investigator.

    Cohort A1 and Cohort A2 - CRC only:

18. Patient has known microsatellite instability-high status.

    Cohort A2 - CRC (navicixizumab + irinotecan) only:

19. Patient is on dialysis.

20. Patient has received hepatic intra-arterial chemotherapy.

    Cohort B1 - Gastric/GEJ cancer only:

21. Patient has experienced weight loss >10% over 2 months prior to first dose of study treatment.
22. Patient has definitive pathologically confirmed HER2 positive metastatic gastric or GEJ adenocarcinoma.

23. Patient has pre-existing Grade ≥2 peripheral neuropathy, according to CTCAE v5.0.

    Cohort C2 - TNBC (navicixizumab + paclitaxel) only

24. Patient has pre-existing Grade ≥2 peripheral neuropathy, according to CTCAE v5.0.

    Cohort D1 - Ovarian cancer only:

25. Patient has non-epithelial ovarian carcinoma.
26. Patient has ovarian tumors with low malignant potential (ie, borderline tumors).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination navicixizumab + paclitaxel; Gastric/GEJ and TNBC cancer patients will be assigned to this treatment arm.	Biological: navicixizumab+paclitaxel; navicixizumab 3 mg/kg Q2W; paclitaxel 80 mg/m2 weekly
Experimental: Combination navicixizumab + irinotecan; CRC patients will be assigned to this treatment arm.	Biological: navicixizumab+irinotecan; navicixizumab 3 mg/kg Q2W; irinotecan 180 mg/m2 Q2W
Experimental: Navicixizumab monotherapy; CRC,TNBC and ovarian cancer patients will be assigned to this treatment arm.	Biological: navicixizumab monotherapy; navicixizumab 3 mg/kg Q2W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	The proportion of patients with a confirmed best overall response (BOR) of complete response (CR) or PR by Response Evaluation Criteria in Solid Tumors, version 1.1 as determined by investigator tumor response assessments	Up to 12 months
Progression Free Survival (PFS)	The time from first dose to the date of first documentation of objective disease progression or death (any cause), whichever occurs first, as determined by investigator tumor response assessments	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE v5.0); clinical laboratory tests; vital sign measurements; electrocardiograms (ECGs); Doppler echocardiograms (ECHOs); physical examinations (PEs)	Up to 12 months
Overall Survival (OS	Defined as the time from first dose to death	Up to 18 months
Time to Response (TTR)	Defined as the time from first dose to first documentation of response (CR or PR)	Up to 12 months
Disease control rate (DCR)	Defined as the proportion of patients with SD or a confirmed BOR of CR or PR	Up to 12 months
Duration of Response (DOR)	Defined as the time from first documentation of response (CR or PR) to documentation of objective disease progression or death due to any cause, whichever occurs first	Up to 18months
Xerna™ TME biomarker	Relationship between antitumor activity of navicixizumab therapy and Xerna™ TME Panel biomarker subtypes	Up to 18 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cancer antigen-125 response	Serum levels of cancer antigen-125 (CA-125) to determine CA-125 response (Cohort D [ovarian cancer] only) and biomarker research through the analysis of tumor and blood samples	Up to 12 months
Immunogenicity	The presence of anti-navicixizumab antibodies (ie, immunogenicity)	Up to 6 months
Navicixizumab Pharmacokinetics	Navicixizumab concentrations by time point	Up to 6 months

Collaborators and Investigators

• Sponsor: OncXerna Theraputics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2022
• Primary Completion (Anticipated): April 15, 2024
• Study Completion (Anticipated): December 15, 2024

Study Registration Dates

• First Submitted: July 7, 2022
• First Submitted That Met QC Criteria: July 7, 2022
• First Posted (Actual): July 12, 2022

Study Record Updates

• Last Update Posted (Actual): December 20, 2022
• Last Update Submitted That Met QC Criteria: December 19, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: navicixizumab
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Paclitaxel; Irinotecan
• Other Study ID Numbers: ONCX-NAV-G201

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: Yes
• Studies a U.S. FDA-regulated device product: No