A Phase I, Open label, First in Human Dose-Escalation and Dose Expansion Study

Phase 1

Recruiting

• Conditions: Malignant neoplasm of other specified ill-defined sites,

• Registration Number: CTRI/2022/09/046061
• Lead Sponsor: Aurigene Discovery Technologies Limited

Brief Summary

This is amulti-center, open-label, First in Human, Phase 1 study of AUR 105 in adultpatients with advanced malignancies.

 The study will have twoparts: a Dose Escalation Part and Dose Expansion Part.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-03-10
• Last Update Posted: 2023-02-15

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: All
• Target Recruitment: 40

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) greater than equal to 60 mL/min (either measured or estimated by the Cockcroft Gault formula).
• (Cockcroft Gault formula for estimated creatinine clearance (eCrCl) : eCrCl (140– Age)xWeight (kg)x(0.85 if Female)/ (72xserum creatinine mg/dL.) 4.
• Ability to swallow and retain oral medications 5.
• Histo pathological diagnosis of a solid tumor, Non Hodgkin lymphoma or Hodgkin Lymphoma Note: The solid tumors must be in Stage IV at screening.
• The lymphoma could be either in Stage III or IV according to Lugano classification (Cheson et al.
• 2014. at screening.
• Evidence of measurable disease per RECIST v1.1 for solid tumors (Eisenhauer et al.
• 2009. and per Lugano Criteria for Lymphoma (Cheson et al.
• 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.
• (Note: Any cancer patient with access to any effective therapy must not be enrolled).

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.
• 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.
• 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) 4.
• Use of any investigational agent within 28 days or 5 half-lives (whichever is longer) prior to Cycle 1 Day 1 5.
• 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 6.
• 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) 8.
• Patients with leukemia or myelodysplastic syndrome or multiple myeloma 9.
• Active infection requiring systemic therapy.
• 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 illness 11 Known active or chronic hepatitis B (HBsAg +ve) or hepatitis C infection (HCV antibody +ve) 12.The patient who is expected to require any other form of antineoplastic therapy or targeted therapy while on study.
• 13.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 14.
• Ongoing cardiac dysrhythmias requiring treatment of any grade or treatment of cardiac dysrhythmias in past 3 months before Cycle 1 Day 1 15.
• 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 pre-dose 16.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 major medical illness eg renal hepatic hematologic gastrointestinal endocrine pulmonary or psychiatric illness social situations or clinically significant laboratory ECG abnormalities at screening any or a combination of illnesses which in the opinion of the PI may either put the patient at risk because of participation in the study or influence the results or the patients ability to participate in the study 17.
• Current swab positive or suspected (under investigation) Covid-19 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 18.
• 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 19.
• Positive pregnancy test for women of child-bearing potential (WOCBP) at the screening or enrolment visit 20.
• 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 or cervical cap).

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary Endpoints	During first 28 Days (Cycle 1)
First cycle DLT	During first 28 Days (Cycle 1)
Safety and tolerability of AUR105 as measured by NCI CTCAE v 5.0	During first 28 Days (Cycle 1)
Recommended Phase 2 Dose (RP2D)	During first 28 Days (Cycle 1)
PK parameters including but not limited to Cmax, Cmin, Tmax, AUC0-t, AUC0-last, MRT and t½	During first 28 Days (Cycle 1)
Comparison of PK parameters in fasting and fed conditions	During first 28 Days (Cycle 1)

Secondary Outcome Measures

Name	Time	Method
Exploratory Endpoints:	PD biomarkers

Trial Locations

Locations (11)

All India Institute of Medical Sciences; 🇮🇳 Anugul, ORISSA, India

HCG Cancer Centre; 🇮🇳 Gulbarga, KARNATAKA, India

HCG City Cancer Centre; 🇮🇳 Krishna, ANDHRA PRADESH, India

Healthcare Global Enterprises Limited; 🇮🇳 Bangalore, KARNATAKA, India

IMS&SUM Hospital; 🇮🇳 Khordha, ORISSA, India

Kailash Cancer Hospital and Research Centre; 🇮🇳 Vadodara, GUJARAT, India

Krupamayi Hospital; 🇮🇳 Aurangabad, MAHARASHTRA, India

Moraya Multi-Speciality Hospital; 🇮🇳 Pune, MAHARASHTRA, India

Omega Hospitals; 🇮🇳 Visakhapatnam, ANDHRA PRADESH, India

PDEAs Ayurved Rugnalaya & Sterling Multispeciality Hospital; 🇮🇳 Pune, MAHARASHTRA, India

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All India Institute of Medical Sciences

🇮🇳Anugul, ORISSA, India

Dr Deepam Pushpam

Principal investigator

9650629370

deepampushpam@gmail.com

Dr Sourav Mishra

Principal investigator

7008651823

drskmishra1984@gmail.com