Patients With Platinum-Resistant Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer MedDRA version: 20.0 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Navicixizumab
Product Code: OMP-305B83
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Navicixizumab
CAS Number: 1638338-43-8
Current Sponsor code: OMP-305B83
Other descr
Sponsors
OncXerna Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient provides signed informed consent to participate in the study prior to undergoing any study procedures, including screening procedures. 2. Patient is =18 years old or age of majority in the country in which they reside, whichever is higher. 3. Patient must have epithelial ovarian, fallopian tube, or primary peritoneal cancer consisting of one of the following histological subtypes: - adenocarcinoma not otherwise specified - clear cell adenocarcinoma - endometrioid adenocarcinoma - malignant Brenner's tumor - mixed epithelial carcinoma - malignant mixed Mullerian - serous adenocarcinoma - transitional cell carcinoma - undifferentiated carcinoma 4. Patients must have received =2 and not more than 5 prior therapies, including at least 1 line of therapy containing bevacizumab (or biosimilar). - Adjuvant/neoadjuvant therapy is counted as only 1 regimen in the absence of intervening progression. - Maintenance therapy (e.g., bevacizumab or a PARP inhibitor will be considered part of the preceding line of therapy [i.e., not counted independently]). - Therapy changed due to toxicity in the absence of progression will be considered part of the same line (i.e., not counted independently). - Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance. - Patients with known BRCA-1 or -2 mutation should have received a prior PARP inhibitor. 5. Patients must be considered platinum-resistant, defined as progression within 6 months from completion of a platinum-containing therapy. The date should be calculated from the last administered dose of platinum-containing therapy. 6. Patient must be considered appropriate for treatment with weekly paclitaxel monotherapy as the next line of therapy. 7. Patient must be willing and able to provide an FFPE archival or core tumor sample for determination of biomarker status on the Xerna™ TME Panel biomarker assay (positive or negative)prior to study treatment. 8. Determination of B+ or B- status on the Xerna™ TME Panel biomarker assay. 9. Presence of at least one measurable lesion, as defined by RECIST v1.1. Previously irradiated lesions can be considered as measurable if disease progression has been unequivocally demonstrated at that lesion since radiation. 10. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1. 11. Adequate organ function defined as: - Absolute neutrophil count (ANC) =1.5 x 109/L. - Hemoglobin =9 g/dL. The patient may have been transfused to meet eligibility criteria; however, hemoglobin should remain stable and =9 g/dL for at least 1 week prior to first dose of study therapy. - Platelet count =100 x 109/L. - Total serum bilirubin =1.5 x institutional upper limit of normal (ULN). Patients with known Gilbert syndrome who have serum bilirubin level =3 x ULN may be enrolled upon discussion with the medical monitor. - Aspartate aminotransferase and alanine aminotransferase =3.0 x ULN or =5 x ULN (based on institutional limits) if there are documented metastases in the liver. - Serum creatinine =1.5 x ULN for the reference laboratory or a calculated creatinine clearance of =30 mL/min by the Cockcroft-Gault equation. - International normalized ratio and activated partial thromboplastin time (aPTT) within 1.5 x the institutional ULN. If a patient is receiving anticoagulant therapy, then prothrombin time/aPTT should be within therapeutic range of intended use. 12. Women of childbearing potential must have a negative serum or urine pregna
Exclusion criteria
Exclusion criteria: 1. Non-epithelial ovarian carcinoma. 2. Ovarian tumors with low malignant potential (i.e., borderline tumors). 3. Primary platinum-refractory disease (defined as progression during or within 4 weeks after completion of the first platinum regimen). 4. Patient has received an anti-angiogenic product other than bevacizumab or biosimilar. 5. Patient has any of the following conditions related to cardiac function: - Symptomatic congestive heart failure (New York Heart Association Class II to IV; Appendix 2). - History of myocardial infarction, cerebral vascular accident, or transient ischemic attacks within 6 months prior to C1D1. - History of cardiac ischemia or heart failure within 6 months prior to C1D1. - Baseline B-type natriuretic peptide (BNP) value >100 pg/mL or N-terminal-proBNP (NT-proBNP)value of > 125 pg/mL. - LVEF 3.0 m/s on Doppler ECHO. - Clinically significant ECG abnormality, as assessed by the investigator. 6. Blood pressure (BP) >140/90 mmHg. Patients taking antihypertensive medications must be taking =2 medications to obtain BP control of =140/90 mmHg. Note: Fixed-dose combination treatments should be considered 2 medications. 7. Pregnant or lactating women. 8. Active/unstable brain metastases including leptomeningeal disease. 9. Known additional malignancy that was progressing or had required active treatment within 2 years prior to the first dose of study medication. Exceptions include malignancies with a negligible risk of metastasis or death, including basal cell basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ). 10. History of bowel obstruction, including sub-occlusive disease, related to the underlying disease and history of abdominal fistula, GI perforation, or intra-abdominal abscess. Evidence of recto sigmoid involvement by pelvic examination or bowel involvement on computed tomography (CT) scan or clinical symptoms of bowel obstruction. 11. Pre-existing Grade =2 peripheral neuropathy, according to the CTCAE v5.0. 12. Active infection requiring IV systemic therapy. 13. Known hypersensitivity to any components of monoclonal antibodies, including navicixizumab or any of its excipients that, in the opinion of the investigator, suggests a high risk for a severe hypersensitivity reaction while on treatment. 14. Known clinically significant bleeding disorder. 15. Current use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes that has not been stable for >14 days prior to C1D1. Note: Prophylactic doses of anticoagulants, low-dose aspirin, and/or non-steroidal anti-inflammatory agents are allowed. 16. Hemoptysis >2.5 mL within 8 weeks prior to C1D1 or serious bleeding from another site within this time frame. 17. Major surgical procedure, or significant traumatic injury within 28 days prior to C1D1, or anticipation of need for major surgical procedure during the study. Note: Placement of a vascular access device will not be considered major surgery. 18. Patients with an uncontrolled seizure disorder or active neurologic disease. 19. Patients with a cardiac aneurysm. 20. Known psychiatric, substance abuse disorder, or geographical travel limitations that would interfere with patient’s ability to cooperate with the requirements of the study. 21. History or current evidence of any condition, therapy, or laboratory abnormality that may confound the results o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To compare the objective response rate (ORR) and evaluate the duration of response (DOR) in patients with B+ disease, as well as in all-comers, treated with navicixizumab in combination with weekly paclitaxel to patients treated with weekly paclitaxel monotherapy • To compare the progression-free survival (PFS) in patients with B+ disease, as well as in all-comers, treated with navicixizumab in combination with weekly paclitaxel to patients treated with weekly paclitaxel monotherapy • To compare the ORR and evaluate the DOR in patients with B+ disease, as well as in all-comers, treated with navicixizumab monotherapy to patients treated with weekly paclitaxel monotherapy;Secondary Objective: • To evaluate overall survival (OS) in patients with B+ disease, as well as in all-comers, treated with navicixizumab in combination with weekly paclitaxel to patients treated with weekly paclitaxel monotherapy • To evaluate whether biomarker status on the Xerna™ TME Panel is a predictive biomarker for ORR, PFS, and OS in patients receiving treatment with navicixizumab either in combination with weekly paclitaxel or as monotherapy Other Secondary Objectives: • To evaluate the PFS and OS in patients treated with navicixizumab monotherapy vs patients treated with weekly paclitaxel monotherapy • To further characterize the antitumor activity and clinical benefit of navicixizumab in combination with weekly paclitaxel in comparison to weekly paclitaxel monotherapy or navicixizumab monotherapy • To characterize concordance between archived and core tumor samples in terms of Xerna™ TME Panel biomarker status;Primary end point(s): • ORR, defined as the proportion of patients with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR), by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) • PFS, defined as the time from randomization to the date of first documentation of objective disease progression or death (any | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • OS, defined as the time from randomization to death • Time to response (TTR), defined as the time from randomization to first documentation of response(CR or PR) • Disease control rate (DCR), defined as the proportion of patients with stable disease (SD) or a confirmed BOR of CR or PR • 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 • Changes in measures of health-related QOL (EORTC QLC-30 and supplemental ovarian cancer module [QLQ-OV28]; EQ-5D-5L) • Concordance in Xerna™ TME Panel biomarker status between archived and core tumor samples collected during the screening period.;Timepoint(s) of evaluation of this end point: As defined in the secondary end point(s) | — |
Countries
Belgium, Canada, France, Germany, Italy, Korea, Republic of, Poland, Romania, Spain, United Kingdom, United States
Contacts
Public ContactSusan MacIntyre
OncXerna Therapeutics, Inc.
Outcome results
None listed