First in Human, Dose Escalation, Dose Expansion Study of AUR105

Study Overview
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Brief Summary
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This is a multi-center, open-label, First in Human, Phase 1 study of AUR 105 in adult patients with advanced malignancies. The study will have two parts: a Dose Escalation Part and Dose Expansion Part.

Detailed Description
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This is a Phase I, Open label First in Human Study in adult patients with relapsed advanced malignancies. The study will have two parts. Dose escalation part and Dose expansion part

Official Title
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A Phase 1, Open Label, Dose Escalation, Dose Expansion, Multicenter, First in Human (FIH) Study Evaluating the Safety, Pharmacokinetics and Pharmacodynamics of Oral AUR105 in Patients With Relapsed Advanced Malignancies (SURYA-1)

Conditions
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Solid Tumor, Adult, Non-hodgkin Lymphoma, Hodgkin Lymphoma

Intervention / Treatment
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* Drug: AUR105


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ≥ 18 years of age Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1 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 (Patients with lymphoma are allowed with Platelet count ≥ 75,000 / μL) 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). (Cockcroft-Gault formula for estimated creatinine clearance [eCrCl]: eCrCl = [140- Age] × Weight [kg] × [0.85 if Female] / [72 × serum creatinine (mg/dL)]). Ability to swallow and retain oral medications Histo-pathological diagnosis of a solid tumor, Non-Hodgkin lymphoma or Hodgkin Lymphoma Evidence of measurable disease per RECIST, v1.1 for solid tumors (Eisenhauer et al. 2009) and per Lugano Criteria for Lymphoma (Cheson et al. 2014). Standard curative measures do not exist, and patient must have exhausted all effective therapies, available locally. 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). At a minimum, lymphoma patients must have received at least 2 prior lines of systemic therapies. These systemic therapies could be either in the stage II, III or IV. Exclusion Criteria: 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. Presence of an 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 5.0 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 Use of moderate / strong CYP3A4 inhibitors/inducers or moderate / strong P-gp inhibitor/inducers within 2 weeks or 5 half-lives (whichever is longer) prior to Cycle 1 Day 1 (The list of these medications is provided in the first four rows of Table 5) Known symptomatic or untreated or recently treated (≤ 6 months of screening) central nervous system (CNS) metastases or CNS lymphoma. Patients with previously treated (> 6 months of screening) CNS metastases or CNS lymphoma 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) Patients with leukemia or myelodysplastic syndrome or multiple myeloma Active infection requiring systemic therapy. 10. 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. Known to be human immunodeficiency virus (HIV) positive or have an acquired immunodeficiency syndrome-related illnessKnown active or chronic hepatitis B (HBsAg +ve) or hepatitis C infection (HCV antibody +ve) The patient who is expected to require any other form of antineoplastic therapy or targeted therapy while on study. 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 Ongoing cardiac dysrhythmias requiring treatment of any grade or treatment of cardiac dysrhythmias in past 3 months, before Cycle 1 Day 1 QTc (Bazzett) interval >450 ms for male patients or >460 ms for female patients on ECG at screening and/or at Cycle 1 Day 1 predose. 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 Current swab-positive or suspected (under investigation) Covid19 infection or fever and other signs or symptoms suggestive of Covid-19 infection with recent contact of person(s) with confirmed Covid-19 infection, at screening or Day 1 of Cycle 1 History of another primary malignancy within 5 years prior to starting study drug, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study. Positive pregnancy test for women of child-bearing potential (WOCBP) at the screening or enrolment visit Lactating women or WOCBP who are neither surgically sterilized nor willing to use reliable contraceptive methods (hormonal contraceptive, IUD, or any double combination of male or female condom, spermicidal gel, diaphragm, sponge, cervical cap)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Dose Escalation 3+3 dose escalation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AUR105 50mg to 750mg<br>Currently planned dose levels in Part 1 are 50mg, 100mg, 200mg, 300mg, 450mg, 600mg and 740mg once daily | Drug: AUR105<br>* Once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Endpoints | First cycle DLT | 28 Days | 
| Primary Endpoints | PK parameters - Cmax | Day 16 | 
| Primary Endpoints | PK parameters- AUC | Day 16 | 
| Primary Endpoints | PK parameters- Tmax | Day 16 | 
| Primary Endpoints | Recommended Phase 2 Dose determination | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exploratory Endpoints: | PD biomarkers (SDMA) | Day 15 | 
| Exploratory Endpoints: | Efficacy assessments overall response rate | Through study completion, an average of 1 year | 
| Exploratory Endpoints: | Efficacy assessments- duration of response | Through study completion, an average of 1 year | 
| Exploratory Endpoints: | Efficacy assessments- PFS | Through study completion, an average of 1 year | 
| Exploratory Endpoints: | Change in Tumor Specific Markers - CA-125 in ovarian cancer | Through study completion, an average of 1 year | 
| Exploratory Endpoints: | Change in Tumor Specific Markers - PSA in Castrate Resistant Prostate Cancer | Through study completion, an average of 1 year | 
| Exploratory Endpoints: | Change in Tumor Specific Markers - CEA in colorectal cancer | Through study completion, an average of 1 year |