A Phase 1, Open Label, Dose Escalation, Dose Expansion, Multicenter, First in Human Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of Oral AUR107 in Patients With Relapsed Advanced Malignancies (SHAKTI-1)
Overview
- Phase
- Phase 1
- Intervention
- AUR107
- Conditions
- Relapsed Malignant Solid Neoplasm
- Sponsor
- Aurigene Discovery Technologies Limited
- Enrollment
- 50
- Locations
- 44
- Primary Endpoint
- Maximum concentration (Cmax) administered under fasting/fed condition
- Status
- Recruiting
- Last Updated
- 15 days ago
Overview
Brief Summary
An open-label, first-in-human, Phase 1 study in adult patients with relapsed advanced malignancies will be done to assess AUR107 safety, tolerability, pharmacokinetics, pharmacodynamics, and optimal biological dose.
Detailed Description
This is a Phase I, Open Label, Dose-Escalation, First-in-Human study in adult patients with select relapsed advanced malignancies. The safety and tolerability of oral AUR107 will be evaluated in patients with selected advanced solid tumors (Non-small cell lung cancer, Gastric cancer, Urothelial cancer, Kidney cancer, Colon cancer, and Esophageal cancer) who do not have any available curative or life-prolonging treatment options and have exhausted all effective locally available therapies. The traditional 3+3 design for dose escalation will be used to evaluate the safety, pharmacokinetics/pharmacodynamics, and determine the Optimal Biological Dose of AUR107 as a single agent. The Optimal Biological Dose will be selected using a totality of safety, PK, and PD data.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Males and females ≥ 18 years of age.
- •Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or
- •Acceptable bone marrow and organ function at screening as described below:
- •ANC ≥ 1500/μL (without WBC growth factor support)
- •Platelet count ≥ 100,000/μL without transfusion support
- •Hemoglobin ≥ 9 g/dL (Transfusion is allowed to achieve this Hb)
- •Total Bilirubin ≤ 1.5 x ULN; (Patients with known Gilbert's syndrome are allowed with a Total Bilirubin ≤ 2.5 x ULN)
- •AST (SGOT) ≤ 3 x ULN (≤ 5 × ULN if known liver metastases)
- •ALT (SGPT) ≤ 3 x ULN (≤ 5 × ULN if known liver metastases)
- •Creatinine clearance (CrCl) ≥ 60 mL/min (either measured or estimated by the Cockcroft-Gault formula).
Exclusion Criteria
- •Systemic anti-cancer therapy, such as chemotherapy, biological therapy, or immunomodulatory drug therapy, received within the past 28 days or 5 half-lives, whichever is longer, from Cycle 1 Day 1 of the study.
- •Note: Concomitant use of low-dose prednisone (up to 10 mg/day) or medroxyprogesterone is allowed.
- •Note: Patients with CRPC (castrate-resistant prostate cancer) should continue to receive ongoing medical castration with LHRH analogs, and such patients are allowed.
- •Presence of acute or chronic toxicity resulting from prior anticancer treatment, with the exception of alopecia or nail changes, that has not resolved to Grade ≤ 1, as determined by NCI CTCAE v 5.
- •Definitive Radiotherapy within the last 21 days of Cycle 1 Day 1 (limited field palliative radiation is allowed and no restrictions during the screening period or during the trial)
- •Use of any investigational agent within 28 days or 5 half-lives (whichever is longer) prior to Cycle 1 Day
- •Use of drugs which are moderate / strong CYP3A4 inducers and/or drugs which are predominantly metabolized by CYP3A4 within 1week or 5 half-lives (whichever is longer) prior to Cycle 1 Day
- •Note: This class of drugs are also prohibited during DLT evaluation period and must be either avoided or used with caution beyond DLT evaluation period.
- •Known symptomatic or untreated or recently treated (≤ 6 months of screening) central nervous system (CNS) metastases. Patients with previously treated (\> 6 months of screening) CNS metastases and are now stable and asymptomatic, from CNS perspective, are allowed.
- •Major surgery ≤ 28 days from Cycle 1 Day 1 (major surgery is defined as a procedure requiring general anesthesia).
Arms & Interventions
AUR107, 5mg to 200mg
Currently, planned dose levels are 5 mg QD, 10 mg QD, 20 mg QD, 40 mg QD, 60 mg QD, 90 mg QD, 135 mg QD, and 200 mg QD
Intervention: AUR107
Outcomes
Primary Outcomes
Maximum concentration (Cmax) administered under fasting/fed condition
Time Frame: Day 8 and Day 9
Compare in fast and fed conditions
Area under curve (AUC) administered under fasting/fed condition
Time Frame: Day 8 and Day 9
Compare AUC in fast and fed conditions
Time to Maximum concentration (Tmax) administered under fasting/fed condition
Time Frame: Day 8 and Day 9
Compare Tmax in fast and fed conditions
Safety of AUR107 as measured by the number of participants with treatment-related adverse events (AE) graded according to NCI CTCAE version 5.0
Time Frame: 28 days
The assessment of safety was based on the frequency of deaths, AEs, SAEs, AEs leading to discontinuation of study drug, and abnormalities in specific clinical laboratory assessments. AEs and laboratory values will be graded for severity according to the NCI CTCAE version 5.0.
Pharmacokinetics: Maximum concentration (Cmax)
Time Frame: Day 1 and Day 15
Maximum concentration of AUR107
Pharmacokinetics: Time to Maximum concentration (Tmax)
Time Frame: Day 1 and Day 15
Tmax in hours
Pharmacokinetics: Mean Residence Time (MRT)
Time Frame: Day 1 and Day 15
Average time the drugs stays in the body
First cycle Dose Limiting Toxicities (DLT)
Time Frame: 28 days
Assess dose limiliting toxicities of AUR107
Optimal Biological Dose
Time Frame: 28 days
Determine optimal Biological dose
Pharmacokinetics: Area under the curve (AUC)
Time Frame: Day 1 and Day 15
Area under the curve (AUC) of AUR 107 in h\* mcg/mL
Pharmacokinetics: Terminal elimination half-life
Time Frame: Day 1 and Day 15
Terminal elimination half-life of AUR 107 in hours