SOT106 is a special cancer medicine designed to find and kill certain cancer cells that carry a marker called LRRC15, while causing less harm to healthy cells. The study consists of two parts, Part A and Part B. The goal of Part A is to collect information about SOT106, understand its effects, and see whether it is safe and well tolerated at different dose levels. Part B of the study collects information on which of the two selected safe dose levels chosen in Part A gives the best balance between benefit and risk.
The trial will consist of the following parts: * Part A: a multinational, multicenter, open-label, TITE-BOIN-guided trial to determine the MTD and RP2Ds, to evaluate the safety, PK, and preliminary efficacy of escalating doses of SOT106 in participants with LRRC15-positive advanced or metastatic osteosarcoma or soft tissue sarcoma (STS) who have received and/or have been determined to be intolerant of all standard of care therapy known to confer clinical benefit. * Part B: This is a randomized, multinational, multicenter, open-label dose optimization trial evaluating the two recommended doses for optimization (RDOs) identified in Part A. After the determination of the MTD in Part A and identification of RDOs, a randomized dose optimization part will be initiated to evaluate the two selected RDOs and to identify the optimal biological dose that offers the best balance between benefit and risk and to evaluate safety and efficacy of SOT106 in participants with advanced unresectable or metastatic osteosarcoma or STS who have no further standard treatment options.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
70
SOT106 is a LRRC15-directed monoclonal antibody conjugated to a linker-payload, Monomethyl auristatin E
Arensia Exploratory Medicine Research Unit, Institute of Oncology
Chisinau, Moldova
Part A: Maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of SOT106
MTD will be selected as guided by the time to-event Bayesian optimal interval (TITEBOIN) design. The RP2D will be selected based on integrated evaluation of the totality of clinical and preclinical data, for all dose levels tested.
Time frame: At the end of Cycle 1 (one cycle is 21 days)
Part B: Optimal dose of SOT106 for subsequent clinical trials
Assessment of the safety and tolerability of two recommended doses under evaluation for dose optimization (RDOs) of SOT106 by evaluation of the occurrence of SOT106 related TEAEs, serious TEAEs, TEAEs leading to premature discontinuation of SOT106, deaths, and clinical laboratory test abnormalities of grade 3 or higher according to NCI CTCAE Version 6.0
Time frame: Cycle 1 Day 1 up to 30 days after the last dose (each cycle is 21 days)
Part B: Objective Response Rate (ORR) of SOT106
Percentage of participants who achieve a Best Overall Response of Complete Response (CR) or Partial Response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Time frame: From Day 1 of Cycle 1 (one cycle is 21 days) until disease progression, initiation of new anticancer therapy, withdrawal of consent, or study discontinuation, whichever comes first, to be assessed up to approximately 10 months
Part B: Duration of Response (DoR) of SOT106
The time from the first documentation of objective response (CR or PR) to the first documented date of progressive disease (PD) according to RECIST v1.1.
Time frame: From the date of first documented objective response until disease progression, initiation of new anticancer therapy, withdrawal of consent, or study discontinuation, whichever comes first, assessed up to approximately 10 months.
Part A: Safety and Tolerability of SOT106
The occurrence of dose-limiting toxicities (DLTs), SOT106-related treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs leading to premature discontinuation of SOT106, deaths, and clinical laboratory test abnormalities of grade 3 or higher according to National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) Version 6.0
Time frame: From Cycle 1 Day 1 (one cycle is 21 days) assessed for approximately 17 months
Part A: Characterization of maximum concentration (Cmax)
Cmax in plasma of total antibody, conjugated antibody and free MMAE
Time frame: From Cycle 1 Day 1 up to approximately 17 months (each cycle is 21 days)
Part A: Characterization of time to maximum concentration (Tmax)
Time to maximum concentration of total antibody, conjugated antibody and free MMAE.
Time frame: From Cycle 1 Day 1 up to approximately 17 months (each cycle is 21 days)
Part A: Characterization of area under the curve
Area under the concentration versus time curve calculated for total antibody, conjugated antibody and free MMAE.
Time frame: From Cycle 1 Day 1 up to approximately 17 months (each cycle is 21 days)
Part A: Preliminary anticancer activity of SOT106
Tumor response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by LRRC15 expression
Time frame: From Day 1 of Cycle 1 (one cycle is 21 days) until disease progression, initiation of new anticancer therapy, withdrawal of consent, or study discontinuation, whichever comes first, to be assessed up to approximately 17 months
Part A: Immunogenicity of SOT106 as Evaluated by Anti-Drug Antibody (ADA) Incidence
Proportion of participants who test positive for ADAs to SOT106.
Time frame: From Cycle 1 Day 1 up to approximately 17 months (each cycle is 21 days)
Part B: Progression-Free Survival (PFS) of SOT106
Progression-free survival is defined as the time from Cycle 1 Day 1 to the first documented date of progressive disease (PD) according to RECIST v1.1, or death from any cause, whichever occurs first
Time frame: From Cycle 1 Day 1 (one cycle is 21 days) until first documented disease progression or death from any cause, assessed up to approximately 10 months
Part B: Characterization of Cmax
Evaluation of the maximum plasma concentration (Cmax) for total antibody, conjugated antibody, and free MMAE payload.
Time frame: From Cycle 1 Day 1 up to approximately 10 months (each cycle is 21 days)
Part B: Characterization of Tmax
Evaluation of the time to maximum plasma concentration (Tmax) for total antibody, conjugated antibody, and free payload.
Time frame: From Cycle 1 Day 1 up to approximately 10 months (each cycle is 21 days)
Part B: Characterization of area under the curve
To characterize the total drug exposure over time (AUC) for total antibody, conjugated antibody, and free payload.
Time frame: From Cycle 1 Day 1 up to approximately 10 months (each cycle is 21 days)
Part B: Immunogenicity of SOT106 as Evaluated by Anti-Drug Antibody (ADA) Incidence
Proportion of participants who test positive for ADAs to SOT106. The potential impact of ADA status on the pharmacokinetic (PK) profiles (Cmax, AUC, Tmax) of SOT106 will be evaluated by comparing PK data between ADA-positive and ADA-negative participants
Time frame: From Cycle 1 Day 1 up to approximately 10 months (each cycle is 21 days)
Part A: Baseline LRRC15 expression in tumor tissue
Baseline LRRC15 expression in tumor tissue, as determined by immunohistochemistry (IHC) and quantified as the percentage of LRRC15-positive tumor cells
Time frame: From Cycle 1 Day 1 up to approximately 17 months (each cycle is 21 days)
Part B: Baseline LRRC15 expression in tumor tissue
Baseline LRRC15 expression in tumor tissue, as determined by immunohistochemistry (IHC) and quantified as the percentage of LRRC15-positive tumor cells
Time frame: From Cycle 1 Day 1 up to approximately 10 months (each cycle is 21 days)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.