This Phase 1, multi-center, open-label, dose escalation and dose optimization study is designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PDx), and preliminary clinical activity of MOMA-313 administered orally as a single agent or combination therapy in patients with homologous recombinant deficient solid tumors.
MOMA-313 is a novel therapeutic agent designed to target homologous recombination (HR)-deficient cancers by inhibiting DNA polymerase theta. MOMA-313 is being developed as a single-agent and in combination with a poly (adenosine diphosphate ribose) polymerase (PARP) inhibitor in patients with HR-deficient advanced (including locally), relapsed or metastatic solid tumors. This phase 1, first-in-human, open-label study of MOMA-313 is primarily intended to evaluate the safety and tolerability of MOMA-313 when administered orally as a single agent (Treatment Arm 1) or in combination with olaparib (Treatment Arm 2). Each treatment arm of the study includes a dose-escalation phase followed by a dose-optimization phase. In the dose-escalation phase of each treatment arm, successive cohorts of patients will receive increasing oral doses of MOMA-313 as a single agent or in combination with olaparib to determine the presumptive optimal biologic dose(s) (OBD) in this population. The dose-optimization phase of each arm will enroll additional patients to support the confirmation of the OBD. The data from this study conducted in patients with HR-deficient advanced (including locally), relapsed or metastatic solid tumors, including safety, tolerability, PK/PDx findings, and antitumor activity, will form the basis for subsequent clinical development of MOMA-313 as a single-agent and in combination with olaparib.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
220
Investigative Site #108
Goodyear, Arizona, United States
RECRUITINGInvestigative Site #101
La Jolla, California, United States
RECRUITINGInvestigative Site #111
San Francisco, California, United States
RECRUITINGInvestigative Site #104
Lake Mary, Florida, United States
RECRUITINGInvestigative Site #110
St Louis, Missouri, United States
RECRUITINGInvestigative Site #103
New York, New York, United States
RECRUITINGInvestigative Site #106
New York, New York, United States
RECRUITINGInvestigative Site #109
Philadelphia, Pennsylvania, United States
RECRUITINGInvestigative Site #107
Myrtle Beach, South Carolina, United States
RECRUITINGInvestigative Site #102
Nashville, Tennessee, United States
RECRUITING...and 8 more locations
Number of participants with AEs, dose-limiting toxicities (DLTs), serious AEs (SAEs), and/or AEs leading to discontinuation
To assess the safety and tolerability of MOMA-313 given as a single-agent or in combination with olaparib
Time frame: From screening until treatment discontinuation (up to 35 months)
Identify the recommended phase 2 dose (RP2D)
Determine the RP2D of MOMA-313 as a single-agent or in combination with olaparib
Time frame: From screening until treatment discontinuation (up to 35 months)
PK parameter: area under curve (AUC) of MOMA-313
Time frame: Up to 6 weeks with sparse sampling up to 35 months
PK parameter: maximum concentration (Cmax) of MOMA-313
Time frame: Up to 6 weeks with sparse sampling up to 35 months
PK parameter: time to maximum concentration of MOMA-313
Time frame: Up to 6 weeks with sparse sampling up to 35 months
PK parameter: half-life of MOMA-313
Time frame: Up to 6 weeks with sparse sampling up to 35 months
Plasma concentration of olaparib
Time frame: Up to 6 weeks with sparse sampling up to 35 months
Objective response rate (ORR)
ORR is defined as the percentage of subjects with evidence of a complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 and/or Prostate Cancer Working Group-3 (PCWG-3).
Time frame: Up to 35 months
Duration of response (DOR)
DOR is defined as time from first documented PR or better to disease progression (as assessed by RECIST v1.1 and/or PCWG-3 by Investigator assessment) or death whichever is earlier for participants who have achieved a CR or PR
Time frame: Up to 35 months
Time to response (TTR)
TTR is defined as the period of time from the date of first dose of study treatment until the first objective documentation of a CR or PR per RECIST 1.1 and/or PCWG-3.
Time frame: Up to 35 months
Progression free survival (PFS)
PFS is time from first dose of study treatment to progressive disease or death from any cause, whichever is earlier, as assessed via RECIST v1.1 and/or PCWG-3 by Investigator assessment
Time frame: Up to 35 months
Disease control rate (DCR)
DCR defined by the proportion of subjects who achieved either a complete response (CR), partial response (PR), or stable disease (SD) at their first scheduled disease assessment according to disease-specific response criteria.
Time frame: Up to 35 months
Overall survival (OS)
OS is defined as the time from first dose of study treatment to the date of death, irrespective of the cause of death
Time frame: Up to 35 months
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