MC# 22-02 - A First-in-Human, Phase I/II, Open-Label, Multi-Center, Dose-Escalation and Dose-Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of the ATR Inhibitor IMP9064 Monotherapy and in Combination with PARP Inhibitor Senaparib in Patients with Advanced Solid Tumors
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Agent(s): IMP9064
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Disease Type(s): Solid Tumor
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Phase(s): I, II
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Drug Classification(s): Small Molecule, Targeted Therapy
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Molecular Target(s): ATR, PARP
Mechanism of Action
IMP9064 is designed to inhibit that function of ATR, a component of the DNA damage repair system in all cells. Inhibition of DNA damage repair interferes with the replication of rapidly dividing cells.
Senaparib (IMP4297) is an inhibitor of PARP 1 and PARP 2, both components of the DNA damage repair system.
Purpose
In this study, the sponsor and investigators want to learn:
- How much IMP9064 can be given, alone and in combination with Senaparib, with an acceptable level of side effects
- The effects of the IMP9064 when given alone and in combination with Senaparib (good and bad)
- How much of the study drugs are absorbed into the blood and how fast they are removed
- If research tests can be used in the future to predict who will benefit from the study drugs
Inclusion Criteria
- Patients must have histologically confirmed diagnosis of the following described below:
- For Part 1: Male or Female patients with histologically or cytologically confirmed AST refractory to or intolerant of available standard-of-care therapy or for which no standard treatment exists
- For Part 2A: Evidence of ATM loss by either pathogenic ATM mutation and/or loss of ATM expression (defined as <1% by immunohistochemistry [IHC]):
- i. Cohort 1: Female patients with advanced endometrial carcinoma and refractory to or intolerant of platinum-based chemotherapy, immunotherapy, and any approved targeted therapy
- ii. Cohort 2: male or female patients with metastatic colorectal cancer refractory to or intolerant of fluoropyrimidine, oxaliplatin, irinotecan, anti-vascular endothelial growth factor therapy, anti-therapy (if RAS wild type), and any approved targeted
- iii. Cohort 3: male or female patients with HER2(-) advanced breast cancer and refractory to or intolerant of chemotherapy (including an anthracycline and a taxane), hormonal therapy (for HR+ disease), approved immunotherapy, and any approved target therapy
- iv. Cohort 4; male patients with mCRPC (progression confirmed using PCWG 3) with ongoing androgen deprivation with gonadotropin-releasing hormone analogue or bilateral orchiectomy, with serum testosterone < 50 ng/dL (<1.73 nmol/L) within 28 days before study entry and refractory to or intolerant of ADT, a second-generation antiandrogen (e.g., enzalutamide and/or abiraterone), a taxane, and any approved targeted therapy. Patients receiving ADT at study entry should continue to do so throughout the study.
- v. Cohort 5: male or female patients with other AST and refractory to or intolerant of available standard-of-care therapy or for which no standard treatment exists
- For Part 2B: Male or female patients with AST with mutation in ARID1A and refractory to or intolerant of available standard-of-care therapy or for which no standard treatment exists
- For Part 2C: Male or Female patients with AST with other selected gene mutations, including BRCA1, CHEK1, CHEK2, FANCA, MSH2, MRE11, PALB2, RAD51, ATRX, CDK12, PARP1, POLD1, XRCC2, NBN, RAD50, SETD2, XRCC3, and DAXX, or RNaseH2A/RNase2B loss (determined by IHC), or low expression of ATM protein (defined as ≥ 1% and ≤ 25% by IHC) and refractory to or intolerant of available standard-of-care therapy or for which no standard treatment exists
- At least one measurable lesion as defined by RECIST version 1.1 (for Part 2). For Cohort 4: At least evaluable lesion (documented by positive bone scan or metastatic lesions on computed tomography [CT] or magnetic resonance imaging [MRI] according to RECIST version 1.1 or PCWG3).
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (Part 1 & 3) and ≤ 2 (for Part 2 & 4) at screening
- For Part 3 and Part 4: Male or female patients with histologically or cytologically confirmed AST refractory to or intolerant of available standard-of-care therapy or for which no standard treatment exists
Exclusion Criteria
- Receipt of any treatment targeting the ATR/CHK1 pathway
Location
- Dallas, TX - Mary Crowley Cancer Research - Medical City
