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. The SRC is also mandated to modify the dose levels within the dose range (125 to 625 mg BID), as well as the schedule to maintain subject safety and best serve the objectives of the study. 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
KAND567 is a drug in capsule and is intended to be orally administered approximately every 12 hours (±1 hour) with an initial loading dose on Day 2 of two times the dose specified for that dose group (e.g., 2 x 250, 2 x 375, 2 x 500, or 2 x 625 mg KAND567, depending on the dose group; in Part 2, this is the RPIID), followed by a KAND567 dose (Day 2, evening dose) that corresponds to the given dose level. On Days 3 to 7, the subjects will be orally administered the specified KAND567 dose (e.g., 250, 375, 500, or 625 mg BID, depending on the dose group; in Part 2, this is the RPIID). During the second week of dosing (Days 8 to 14) in Part 1 and Part 2, the subjects will be orally administered KAND567 at a dose of 250 mg BID. One treatment cycle is defined as a 21-day period, and each subject will receive up to 6 treatment cycles (or until unacceptable toxicity or disease progression).
Carboplatin will be administered i.v. according to standard of care at a dose of AUC 5. One cycle is defined as a 21-day period with chemotherapy given on Day 1. Each subject will receive up to 6 treatment cycles (or until unacceptable toxicity or disease progression). The carboplatin dose should be calculated using the Calvert formula: Carboplatin dose (mg) = target AUC 5 × (GFR + 25). GFR should be calculated using the Cockcroft-Gault formula. The maximum carboplatin dose is based on a calculated GFR that is capped at 125 mL/min for subjects with normal renal function.
Odense University Hospital
Odense, Denmark
Oslo University Hospital
Oslo, Norway
Skåne University Hospital
Lund, Sweden
Karolinska University Hospital
Solna, Sweden
Evaluate the safety and tolerability of KAND567 in combination with carboplatin therapy in recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, as measured by the occurence of adverse events (AEs)
Measured by occurence of AEs and serious adverse events (SAEs)
Time frame: From the first IMP administration to the subject (Day 1) until the end of study visit (Week 20)
Evaluate the safety and tolerability of KAND567 in combination with carboplatin therapy in recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, as measured by the occurrence of dose limiting toxicities (DLTs)
Measured by the occurrence of DLTs
Time frame: From the first IMP administration to the subject (Day 1) until the end of study visit (Week 20)
Evaluate the safety and tolerability of KAND567 in combination with carboplatin therapy in recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, as measured by vital signs
Measured by the occurrence of clinically abnormal vital signs
Time frame: From the first IMP administration to the subject (Day 1) until the end of study visit (Week 20)
Evaluate the safety and tolerability of KAND567 in combination with carboplatin therapy in recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, as measured by ECG
Measured by the occurrence of clinically abnormal electrocardiography (ECG)
Time frame: From the first IMP administration to the subject (Day 1) until the end of study visit (Week 20)
Evaluate the safety and tolerability of KAND567 in combination with carboplatin therapy in recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, as measured by lab safety tests
Measured by the occurrence of clinically abnormal lab test results (routine clinical chemistry, haematology, and urinalysis)
Time frame: From the first IMP administration to the subject (Day 1) until the end of study visit (Week 20)
Determine the Recommended Phase II Dose (RPIID) of KAND567 in combination with carboplatin therapy in recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer
In Part 1/Phase Ib, RPIID of KAND567 in combination with carboplatin therapy will be determined based on safety and tolerability (DLTs).
Time frame: From the first KAND567 IMP administration to the subject (Day 2) until the end of study visit (Week 20).
Overall Response Rate (ORR)
Evaluate ORR according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and Gynecologic Cancer Intergroup (GCIG) definitions, i.e., best overall response in subjects with measurable disease, or without measurable disease who are evaluable by CA 125.
Time frame: Week 12 and 18
Progression-Free Survival (PFS)
Evaluate PFS according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and Gynecologic Cancer Intergroup (GCIG) definitions, i.e., the time from start of treatment to disease progression or death.
Time frame: From the first IMP administration to the subject (Day 1) to Week 12 and 18
Overall survival (OS)
Evaluate OS according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and Gynecologic Cancer Intergroup (GCIG) definitions, i.e., the time from the start of treatment to death due to any cause.
Time frame: From the first IMP administration to the subject (Day 1) until the end of study visit (Week 20)
Disease control rate (DCR)
Evaluate DCR, i.e., Complete response (CR) + Partial response (PR) + Stable disease (SD), according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and Gynecologic Cancer Intergroup (GCIG) definitions, where: CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameter; and SD= Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study.
Time frame: Week 12 and 18
Duration of response
Evaluate duration of response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and Gynecologic Cancer Intergroup (GCIG) definitions, i.e., time from documentation of tumor response to disease progression.
Time frame: From the first IMP administration to the subject (Day 1) until the end of study visit (Week 20)
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Change in pain score
Change in pain score (patient reported outcome), as measured by the Numeric Rating Scale (NRS). The NRS is a scale rating pain from "no pain" to "worst pain possible" from 0 to 10, where a higher value indicates greater pain intensity.
Time frame: From baseline (Week 1) to Weeks 4, 7, 10, 13, 16 and 20.
Determine the plasma exposure of KAND567
Blood samples will be collected for the determination of concentrations of KAND567 in plasma. The determination of the total concentration of KAND567 in plasma will be carried out using Liquid Chromatography - Tandem Mass Spectrometry (LC-MS/MS). KAND567 PK drug concentration data will be graphically visualized together with normalized PK drug concentration data from the previous KAN0001 study (i.e., no formal PK analysis will be performed).
Time frame: For each 21-day treatment cycle, on Day 7 (0, 1, 2, and 4 hours after KAND567 morning dose) and Day 14 (0, 2 and 4 hours after KAND567 morning dose). Each subject receives up to 6 treatment cycles (or until unacceptable toxicity or disease progression)