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

NCT06087289 | Completed Phase 1 DMC

• 3 other identifiers: KAN00072024-515572-13-002022-002792-11
• Study Type: interventional
• Target: 18
• Locations: 3 countries
• Sites: 4

Brief 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. 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.

Conditions

Epithelial Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer

Keywords

Fractalkine; Ovarian cancer

Outcome Measures

Primary Outcomes (6)

• 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)

  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

  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

  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)

  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)

  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).

  From the first KAND567 IMP administration to the subject (Day 2) until the end of study visit (Week 20).

Secondary Outcomes (7)

• Overall Response Rate (ORR)

  Week 12 and 18

• Progression-Free Survival (PFS)

  From the first IMP administration to the subject (Day 1) to Week 12 and 18

• Overall survival (OS)

  From the first IMP administration to the subject (Day 1) until the end of study visit (Week 20)

• Disease control rate (DCR)

  Week 12 and 18

• Duration of response

  From the first IMP administration to the subject (Day 1) until the end of study visit (Week 20)

Study Arms (2)

Part 1: Dose escalation to determine Recommended Phase II Dose (RPIID)

EXPERIMENTAL

Part 1 of the study will include escalating doses of KAND567 administered in combination with carboplatin (according to standard of care) to approximately 10 subjects in total (may range from 6 to 24 subjects depending on DLTs). Carboplatin will be given on Day 1 of the 21-day cycle at a dose of AUC 5 according to standard of care. KAND567 will be orally administered during the first 2 weeks (Days 2 to 14) of each 21-day carboplatin cycle for up to 6 treatment cycles (or until unacceptable toxicity or disease progression). KAND567 dose escalation will apply for the first week (Days 2 to 7) of the treatment cycle. During the second week of the treatment cycle (Days 8 to 14), KAND567 will be administered at a fixed dose of 250 mg BID to all subjects. Doses of KAND567 will be escalated according to an adaptive, intra-individual dose escalation design.

Drug: KAND567; Drug: Carboplatin

Part 2: Expansion cohort to evaluate RPIID

EXPERIMENTAL

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. Carboplatin will be given on Day 1 of the 21-day cycle at a dose of AUC 5 according to standard of care. For KAND567, the RPIID will be orally administered to the cohort during the first week of each carboplatin cycle (Days 2 to 7). During the second week of the treatment cycle (Days 8 to 14), KAND567 will be administered at 250 mg BID. Up to 6 treatment cycles will be given (or until unacceptable toxicity or disease progression).

Drug: KAND567; Drug: Carboplatin

Interventions

KAND567 DRUG

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).

Also known as: Fractalkine

Part 1: Dose escalation to determine Recommended Phase II Dose (RPIID); Part 2: Expansion cohort to evaluate RPIID

Carboplatin DRUG

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.

Part 1: Dose escalation to determine Recommended Phase II Dose (RPIID); Part 2: Expansion cohort to evaluate RPIID

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• \*Prior treatment with PARPi is allowed. In bevacizumab-naive patients, bevacizumab can be included as part of treatment after tumor progression on study drugs according to local clinical practice
• Participants must have had platinum-based chemotherapy in the first-line setting (at primary treatment or 1st relapse requiring chemotherapy)
• 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. Non-measurable disease must be evaluable using GCIG CA 125 criteria (CA 125 ≥ 2 x upper limit of normal \[ULN\]). If the subject has only 1 measurable lesion, this should not be the same lesion used for biopsy, nor should it be in a previously irradiated area.
• 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 ULN or calculated creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault formula, Total bilirubin ≤ ULN, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ ULN
• 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 for the study duration and 6 months afterwards. She must use contraceptive methods with a failure rate of \< 1% to prevent pregnancy\* and drug exposure of a partner. Male partners must refrain from donating sperm from their partner's first IMP dose until 6 months after their partner's last IMP dose.
• \* Combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device (IUD) or intrauterine hormone-releasing system (IUS); bilateral tubal occlusion, vasectomy, and sexual abstinence.
• Willingness and ability to comply with study procedures, visit schedules, study restrictions and requirements

You may not qualify if:

• Primary platinum-refractory disease, defined as tumor progression during or within 12 weeks from end of first platinum treatment
• Concurrent cancer therapy (including anti-hormonal therapy for breast cancer unless it is omitted at the latest at study enrollment).
• Received other than platinum-containing therapy for primary disease (first-line treatment)
• Received non-platinum-containing chemotherapy line (e.g. weekly paclitaxel) in treatment of recurrent ovarian cancer. Maintenance with bevacizumab and/or PARP-inhibitor is allowed.
• Treatment with an investigational agent concurrently, or where the last dose was administered within 5 elimination half-lives or where pharmacological activity may still be present as assessed by the Investigator.
• Previous malignant disease: subjects are not eligible for the study if actively being treated for invasive cancer other than ovarian cancer. Subjects with previous malignant disease other than ovarian cancer who are relapse-free and treatment-free for more than three years may enter this study (exception: anti-hormonal therapy, which must be omitted at the latest at study enrollment). Subjects with previous history of in situ carcinoma, stage 1A cervical cancer or non-invasive basal cell and squamous cell skin carcinoma can enter this trial.
• Immunodeficiency or organ transplant. Autoimmune or inflammatory condition that requires immunosuppressive or steroid therapy during the course of the study. Subjects using immunosuppressive medications within 14 days prior to the first IMP dose, except for topical medications (intranasal, inhaled, local injection, systemic \[prednisolone equivalent 10 mg/day or less\]) or as needed for hypersensitivity reactions such as CT scan premedication.
• 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 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

Sponsors & Collaborators

• Novakand Pharma AB: lead
• Nordic Society of Gynaecological Oncology - Clinical Trials Unit: collaborator

Study Sites (4)

Odense University Hospital

Odense, 5000, Denmark

Location

Oslo University Hospital

Oslo, 0424, Norway

Location

Skåne University Hospital

Lund, 221 85, Sweden

Location

Karolinska University Hospital

Solna, 171 76, Sweden

Location

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

Chemokine CX3CL1; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Chemokines, CX3C; Chemokines; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Membrane Proteins; Chemotactic Factors; Biological Factors; Inflammation Mediators; Coordination Complexes; Organic Chemicals

Study Officials

• Hanna Dahlstrand, MD/PhD

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2023
• First Posted: October 17, 2023
• Study Start: April 26, 2023
• Primary Completion: April 3, 2025
• Study Completion: April 3, 2025
• Last Updated: June 8, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1); NO (1); SE (2)