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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05453825
• Other study ID #: ONCX-NAV-G201
• Status: Recruiting
• Phase: Phase 2
• Start date: August 5, 2022
• Est. completion date: December 15, 2024

Study information

• Verified date: January 2023
• Source: OncXerna Theraputics, Inc.
• Contact: OncXerna Therapeutics
• Phone: 781-907-7810
• Email: medical[@]oncxerna.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: December 15, 2024
• Est. primary completion date: April 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Colorectal Cancer
• Gastric Cancer
• Ovarian Cancer
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Biological:
• navicixizumab+paclitaxel
navicixizumab 3 mg/kg Q2W; paclitaxel 80 mg/m2 weekly
• navicixizumab+irinotecan
navicixizumab 3 mg/kg Q2W; irinotecan 180 mg/m2 Q2W
• navicixizumab monotherapy
navicixizumab 3 mg/kg Q2W

Locations

Country	Name	City	State
United States	Northside Hospital	Atlanta	Georgia
United States	Hematology Oncology Clinic	Baton Rouge	Louisiana
United States	The Zangmeister Cancer Center	Columbus	Ohio
United States	Genesis Cancer Center	Hot Springs	Arkansas
United States	Keck Medicine of USC	Los Angeles	California
United States	Tennessee Oncology	Nashville	Tennessee
United States	New York University - Langone Health - Perlmutter Cancer Center	New York	New York
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
OncXerna Theraputics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Immunogenicity	The presence of anti-navicixizumab antibodies (ie, immunogenicity)	Up to 6 months
Other	Navicixizumab Pharmacokinetics	Navicixizumab concentrations by time point	Up to 6 months
Primary	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
Primary	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	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
Secondary	Overall Survival (OS	Defined as the time from first dose to death	Up to 18 months
Secondary	Time to Response (TTR)	Defined as the time from first dose to first documentation of response (CR or PR)	Up to 12 months
Secondary	Disease control rate (DCR)	Defined as the proportion of patients with SD or a confirmed BOR of CR or PR	Up to 12 months
Secondary	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
Secondary	Xerna™ TME biomarker	Relationship between antitumor activity of navicixizumab therapy and Xerna™ TME Panel biomarker subtypes	Up to 18 months