A Phase I clinical trial evaluating the Safety, Tolerability, and Efficacy of Oral AUR107 in Patients with Advanced Cancer

Phase 1

Conditions: Health Condition 1: C801- Malignant (primary) neoplasm, unspecified

Registration Number: CTRI/2023/05/052954

Lead Sponsor: Aurigene Oncology Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Open to Recruitment

Sex: Not specified

Target Recruitment: 0

Inclusion Criteria

1.Males and females = 18 years of age.

2.Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1.

3.Acceptable bone marrow and organ function at screening as described below:

a.ANC = 1500/µL (without WBC growth factor support).

b.Platelet count = 100,000/µL without transfusion support.

c.Hemoglobin = 9 g/dL (Transfusion is allowed to achieve this Hb).

d.Total Bilirubin = 1.5 x ULN; (Patients with known Gilbert’s syndrome are allowed with a Total Bilirubin = 2.5 x ULN).

e.AST (SGOT) = 3 x ULN (= 5 × ULN if known liver metastases).

f.ALT (SGPT) = 3 x ULN (= 5 × ULN if known liver metastases).

g.Creatinine clearance (CrCl) = 60 mL/min (either measured or estimated by the Cockcroft-Gault formula).

4.Ability to swallow and retain oral medications.

5.Histo-pathological diagnosis of a solid tumor.

Note: The solid tumors must be in Stage IV at screening.

6.Evidence of measurable disease per RECIST, v1.1 for solid tumors (Eisenhauer et al. 2009).

7.Standard curative measures do not exist, and patient must have exhausted all effective therapies, available locally.

Notes:

7a. At a minimum, solid tumor patients must have received at least two lines of systemic therapies in the metastatic incurable settings (these two lines must be in the metastatic setting and not in the earlier stage of cancer).

7b. Any cancer patient with access to any effective therapy must not be enrolled.

Exclusion Criteria

1.Systemic anti-cancer therapy, such as chemotherapy, or biological therapy, immunomodulatory drug therapy, received within the past 28 days or 5 half-lives, whichever is longer, from the 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 analogues, and such patients are allowed.

2.Presence of an acute or chronic toxicity resulting from prior anti-cancer treatment, with the exception of alopecia or nail changes, that has not resolved to Grade = 1, as determined by NCI CTCAE v 5.0.

3. 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 1.

4.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 1 (The list of these medications is provided in specific rows within Table 5).

•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.

5.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.

6.Major surgery = 28 days from Cycle 1 Day 1 (major surgery is defined as a procedure requiring general anesthesia).

7.Patients with leukemia, myelodysplastic syndrome, multiple myeloma, or lymphoma.

8.Active infection requiring systemic therapy.

Note: Prophylactic use of antibiotics is allowed. Any infection detected during screening period which is resolved adequately according to investigator before the Cycle 1 Day 1, is allowed.

9.Known to be human immunodeficiency virus (HIV) positive or have an acquired immunodeficiency syndrome-related illness.

10.Known active or chronic hepatitis B (HBsAg +ve) or hepatitis C infection (HCV antibody +ve).

11.The patient who is expected to require any other form of antineoplastic therapy or targeted therapy while on study.

12.Uncontrolled congestive heart failure (New York Heart Association [NYHA] Class 2-4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, or transient ischemic attack, or pulmonary embolism within 3 months prior to Cycle 1 Day 1.

13.Ongoing cardiac dysrhythmias requiring treatment of any grade or treatment of cardiac dysrhythmias in past 3 months, before Cycle 1 Day 1.

14.QTc (Bazzett) interval >460 ms on ECG at screening and/or at Cycle 1 Day 1 pre-dose.

15.Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or significant gastritis, active bleeding diatheses, presence of any

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
•First cycle Dose Limiting Toxicities (DLT) <br/ ><br>•Safety and tolerability of AUR107 as measured by NCI CTCAE v 5.0 <br/ ><br>•Optimal Biological Dose (OBD) <br/ ><br>•PK parameters including but not limited to Cmax, Cmin, Tmax, AUC0-t, AUC0-last, MRT and t½ <br/ ><br>•Comparison of PK parameters in fasting and fed conditions <br/ ><br>Timepoint: 28 days <br/ ><br> <br/ ><br>

Secondary Outcome Measures

Name	Time	Method
•PD biomarkers <br/ ><br>•Efficacy assessments: overall response rates, duration of response, PFS, etc., as measured by RECIST 1.1 response criteria for solid tumor (Eisenhauer et al. 2009) <br/ ><br>•Change in Tumor Specific Markers like PSA in Castrate Resistant Prostate Cancer, CA-125 in ovarian cancer, CEA in colorectal cancer <br/ ><br>Timepoint: 28 days <br/ ><br>