Phase 1 safety study of the antibody-drug conjugate (ADC) XMT-1536 (upifitamab rilsodotin) administered as an intravenous infusion once every four weeks in combination with Carboplatin in participants with high-grade serous ovarian cancer (HGSOC, including fallopian tube and primary peritoneal cancer). The trial consists of dose escalation (DES) and expansion (EXP) portion. In addition to safety assessments, the pharmacokinetics of the drug will be assessed along with ADC activity.
This trial is an open-label, multi-center Phase 1 study of upifitamab rilsodotin administered as an intravenous infusion once every 28 days in combination with Carboplatinin patients with high-grade serous ovarian cancer (HGSOC, including fallopian tube and primary peritoneal cancer). The trial consists of dose escalation (DES) and expansion (EXP) portion. The primary objective of the dose escalation (DES) portion is to establish the maximum tolerated dose (MTD) for upifitamab rilsodotin in combination with Carboplatin. In the EXP portion of the trial, participants will initiate treatment at the MTD or recommended phase 2 dose (RP2D) determined in the DES for the combination.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
31
Drug: XMT-1536 (Upifitamab Rilsodotin) XMT-1536 (Upifitamab Rilsodotin) will be administered on Day 1 of each 28-day cycle until disease progression, unacceptable toxicity, or either the patient or study physician determines it is in the best interest of the patient to discontinue participation in the study Other Names: * XMT-1536 * UpRi Drug: Carboplatin Carboplatin will be administered on Day 1 on each of the first six 28 day cycles.
Drug: XMT-1536 (Upifitamab Rilsodotin) XMT-1536 (Upifitamab Rilsodotin) will be administered on Day 1 of each 28-day cycle until disease progression, unacceptable toxicity, or either the patient or study physician determines it is in the best interest of the patient to discontinue participation in the study Other Names: * XMT-1536 * UpRi Drug: Carboplatin Carboplatin will be administered on Day 1 on each of the first six 28 day cycles.
START Midwest
Grand Rapids, Michigan, United States
DES: Maximum tolerated dose (MTD) for Upifitamab Rilsodotin with carboplatin
Determine the MTD of Upifitamab rilsodotin in combination with carboplatin by evaluating adverse events in combination with carboplatin
Time frame: Up to 24 weeks, from the date of first dose until unacceptable side effects or a dose-limiting toxicity is met
EXP: Assess the feasibility of Upifitamab rilsodotin combination initiated at MTD or RP2D
Assess the feasibility of Upifitamab rilsodotin combination initiated at MTD or RP2D Assess the feasibility of Upifitamab rilsodotin combination initiated at MTD or RP2D, where the regimen will be considered feasible if at least 60% of participants complete at least four cycles of the carboplatin-upifitamab rilsodotin combination, allowing for standard treatment modifications, without discontinuing treatment earlier for reasons other than disease progression
Time frame: First dose up until 30 days after study termination
DES and EXP: Safety and Tolerability, by observance of frequency and grade of adverse events based on CTCAE v5.0.
DES and EXP: Safety and Tolerability, by observance of frequency and grade of adverse events based on CTCAE v5.0.
Time frame: First dose up until 30 days after study termination
DES and EXP: Time of maximum observed concentration of carboplatin
Determine the pharmacokinetics of carboplatin
Time frame: Daily for one week after first dose; weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent
DES and EXP: Maximum concentration of XMT-1536 (Upifitamab rilsodotin)
Determine the pharmacokinetics of XMT-1536 (Upifitamab rilsodotin)
Time frame: weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses
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DES and EXP: Maximum concentration of carboplatin
Determine the pharmacokinetics of carboplatin
Time frame: Weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses
DES and EXP: Area under the concentration curve of the last measurable concentration of XMT-1536 (upifitamab rilsodotin)
Determine the pharmacokinetics of XMT-1536 (Upifitamab rilsodotin)
Time frame: Weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses
DES and EXP: Area under the concentration curve of the last measurable concentration of carboplatin
Determine the pharmacokinetics of carboplatin
Time frame: Weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses
DES and EXP: Anti-neoplastic effects of XMT-1536 (Upifitamab rilsodotin) in combination with carboplatin
ORR (by RECIST 1.1)
Time frame: Every 8 weeks for the first 12 months, then every 12 weeks on treatment
DES and EXP: Anti-neoplastic effects of XMT-1536 (Upifitamab rilsodotin) in combination with carboplatin
DOR
Time frame: Every 8 weeks for the first 12 months, then every 12 weeks on treatment
DES and EXP: Anti-neoplastic effects of XMT-1536 (Upifitamab rilsodotin) in combination with carboplatin
DCR
Time frame: Every 8 weeks for the first 12 months, then every 12 weeks on treatment
DES and EXP: Anti-neoplastic effects of XMT-1536 (Upifitamab rilsodotin) in combination with carboplatin PFS (by RECIST 1.1)
PFS (by RECIST 1.1)
Time frame: Every 8 weeks for the first 12 months, then every 12 weeks on treatment
DES and EXP: Anti-neoplastic effects of XMT-1536 (Upifitamab rilsodotin) in combination with carboplatin
OS
Time frame: Every 90 days
DES and EXP: Assess the correlation of tumor expression of NaPi2b and objective tumor response
Potential NaPi2b protein or RNA levels of NaPi2b transcript or other genes related to cancer measured in tumor samples Blood-based biomarkers, which may include serum cytokines, circulating immune cells, and circulating tumor cells
Time frame: Every 8 weeks for the first 12 months, every 12 weeks on treatment, every 90 days for OS