A Study to Evaluate the Safety of KAND567, in Combination With Carboplatin Therapy, in Women With Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

• Status: Recruiting
• Trial end date: 2024-06-30
• Target enrollment: 0
• Participant gender: Female

Summary

The study is a multicenter, Phase Ib/IIa, open-label, dose-escalation study to evaluate the safety and tolerability of orally administered KAND567 in combination with carboplatin therapy, and to determine the Recommended Phase II Dose (RPIID) of KAND567 in combination with carboplatin in subjects with recurrent platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.

In Part 1, dose escalation will be based on the recommendation of the Safety Review Committee (SRC) after review of the emerging safety and tolerability information. Once the RPIID has been identified in Part 1, the SRC may recommend to the Sponsor to start Part 2.

An expansion cohort will be enrolled in Part 2 of the study to further evaluate the RPIID (approximately 20 subjects; may range from 6 to 24 subjects, depending on Part 1). If the number of subjects with confirmed CX3CR1 expression in tumor cells is below 50%, an additional 15 subjects may be included in Part 2 of the study.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kancera AB
• Collaborator: Nordic Society of Gynaecological Oncology - Clinical Trials Unit
• Treatments: Carboplatin

Criteria

Inclusion Criteria:

• Histologically verified high-grade serous or high-grade endometrioid epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer

• Participants must have recurrent disease, defined as: 1st relapse 3 to 6 months after completion of the last dose of primary platinum containing treatment, or 2nd or 3rd relapse within 6 months after completion of the last dose of the latest platinum-containing regimen (platinum-free interval within 6 months)

• Participants must have had platinum-based chemotherapy in the first-line setting (primary treatment)

• For BRCA status, samples must be available for analysis; for HRD status, samples should be available for analysis, if possible. If not already analyzed, the subject agrees to undergo analysis of HRD and BRCA status on primary tumor tissue and/or recurrent tumor tissue

• ECOG performance status 0-2

• Subjects must have at least 1 measurable disease according to RECIST 1.1 guidelines

• Able to take oral medications

• Adequate organ function: Absolute neutrophil count ≥ 1.5 x 10^9/L, Platelets > 100 x 10^9/L, Hemoglobin ≥ 80 g/dl, Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault formula, Total bilirubin ≤ 1.5 x ULN, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN, and Serum albumin ≥ 30 g/L.

• Consent to biopsy taken prior to starting treatment and Week 8 (± 1 week) of treatment

• At least 18 years of age

• Life expectancy of at least 12 weeks

• Women of childbearing potential must use adequate birth control

• Willingness and ability to comply with study procedures, visit schedules, study restrictions and requirements

• Able to fully understand and participate in study-related procedures, including compliance and patient reported outcome

• Written informed consent. Subjects must give informed consent prior to any study-specific procedure

Exclusion Criteria:

• Ovarian sarcomas, small cell carcinoma with neuroendocrine differentiation, non-epithelial cancers, and cancer types not mentioned in the inclusion criteria

• Primary platinum-refractory disease, defined as tumor progression during or within 12 weeks from end of first platinum treatment

• Concurrent cancer therapy

• Received other than platinum-containing therapy for primary disease (first-line treatment)

• Received non-platinum-containing chemotherapy in recurrent setting

• Treatment with an investigational agent concurrently, or within the past 3 months

• Previous malignant disease: subjects are not eligible for the study if actively being treated for invasive cancer other than ovarian cancer

• Immunodeficiency or organ transplant. Autoimmune or inflammatory condition that requires immunosuppressive or steroid therapy during the course of the study

• Live vaccines within 28 days prior to the first IMP dose

• Major surgery within 28 days prior to the first IMP dose, or not recovered from previous surgery to CTCAE (v5) grade 1 equivalent

• Active infection including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)

• Transient ischemic attack (TIA) or stroke, including bleeding, within the past 6 months

• Brain and/or liver metastases

• Major cardiac dysfunction defined as > NYHA II

• Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug

• Serious, uncontrolled, and active infection at enrollment, as determined by the Investigator

• Pregnancy or breastfeeding

• Persistence of clinically relevant therapy-related toxicity from previous chemotherapy (any grade 3-4 toxicity or grade ≥ 2 neuropathy)

• Current use of drugs sensitive to CYP3A4 inhibition which cannot be paused or switched to an alternative within the same class of medication for the period of IMP administration

• Continuous use of herbal preparations (e.g., St. John's wort) within 2 weeks prior to enrollment

• Any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the participant (e.g., compromise well-being) or that could prevent, limit, or confound the protocol-specified assessments