First in Human, Dose Escalation, Dose Expansion Study of AUR105 (SURYA-1)

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Hodgkin Lymphoma; Solid Tumor, Adult; Non-hodgkin Lymphoma
• Intervention / Treatment: Drug: AUR105

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Divyesh Dr Mandavia; Phone Number: 9427181182; Email: divyesh_m@aurigene.com
• Study Contact Backup: Name: Suresh Mr Oduru; Phone Number: 9866225593; Email: suresh_o@aurigene.com

Study Locations

• India
  • Bhubaneswar, India, 751003
    • Recruiting
    • IMS&SUM Hospital
    • Contact: Lalatendu Dr Moharana; Phone Number: 9538752579; Email: drlalatendu@gmail.com
  • New Delhi, India, 110029
    • Recruiting
    • ALL India Institute of medical Scieneces
    • Contact: Deepam Dr Pushpam; Phone Number: 9650629370; Email: deepampushpam@gmail.com
  • Andhra Pradesh
    • Vijayawada, Andhra Pradesh, India, 520002
      • Recruiting
      • HCG City Cancer Center
      • Contact: Lakshmi Priyadarshini, MBBS; Phone Number: 9966030988; Email: priyadarshini006@gmail.com
    • Visakhapatnam, Andhra Pradesh, India, 530040
      • Recruiting
      • Omega Hospitals
      • Contact: Bellala Ravi Shankar, MBBS; Phone Number: 9849123256; Email: dr.bellalaravishankar@gmail.com
  • Gujarat
    • Vadodara, Gujarat, India, 391760
      • Recruiting
      • Kailash Cancer Hospital and Research Centre
      • Contact: Santhosh Dr Vandanasetti; Phone Number: 9427423693; Email: Vandanasetti.santhosh@greenashram.org
  • Maharasthra
    • Pune, Maharasthra, India, 411033
      • Recruiting
      • Moraya Multi-Speciality Hospital
      • Contact: Rakesh Dr Neve; Phone Number: 9881143140; Email: rakesh.neve@gmail.com
  • Maharastra
    • Aurangabad, Maharastra, India, 431001
      • Recruiting
      • Krupamayi Hospital
      • Contact: Viraj Vijay Dr Borgaonkar; Phone Number: 9673073555; Email: viraj.oncosurg@gmail.com
  • Odisha
    • Bhubaneswar, Odisha, India, 751019
      • Recruiting
      • All India Institute of Medical Sciences
      • Contact: Sourav Dr Mishra; Phone Number: 7008651823; Email: drskmishra1984@gmail.com
    • Bhubaneswar, Odisha, India, 751007
      • Recruiting
      • Sparsh Hospital and Critical Care
      • Contact: Ghanshyam Dr Biswas; Phone Number: 9937500878; Email: drgbiswas@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 97 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

  1. 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).
  2. 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Aurigene Discovery Technologies Limited

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2022
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): May 30, 2026

Study Registration Dates

• First Submitted: October 5, 2022
• First Submitted That Met QC Criteria: October 28, 2022
• First Posted (Actual): November 4, 2022

Study Record Updates

• Last Update Posted (Estimated): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: AUR105-101; CTRI/2022/09/046061 (Other Identifier: Clinical Trial registry of India)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No