A Phase I clinical trial evaluating the Safety, Tolerability, and Efficacy of Oral AUR108 in Patients with Relapsed Advanced Lymphoma

Phase 1

Conditions: Health Condition 1: C833- Diffuse large B-cell lymphomaHealth Condition 2: C82- Follicular lymphomaHealth Condition 3: C84- Mature T/NK-cell lymphomasHealth Condition 4: C817- Other Hodgkin lymphoma

Registration Number: CTRI/2023/08/056321

Lead Sponsor: Aurigene Oncology Limited(Subsidiary of Dr. Reddy’s Laboratories 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 or 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 = 1000/µL (without WBC growth factor support)

b. Platelet count = 75,000/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) = 30 mL/min .

4. Ability to swallow and retain oral medications

5. Histo-pathological diagnosis of a Non-Hodgkin lymphoma or Hodgkin Lymphoma

Note: The lymphoma should be either in Stage III or IV according to Lugano classification (Cheson BD et al, 2014) at screening.

6. In the case of subjects who have lymphoma for which high-dose chemotherapy and autologous stem cell transplantation (HDASCT) is considered a standard curative therapy, eligibility for this study requires that the subject’s disease has relapsed after HDASCT, that the subject is not eligible for HD-ASCT, or that the subject has refused HD-ASCT.

7. In the case of subjects who have lymphoma for which CAR-T therapy is considered a standard therapy, eligibility for this study requires that the subject’s disease has relapsed after CAR-T, or that the subject has refused CAR-T, or that the CAR-T therapy is not accessible to the patient.

8. Evidence of measurable disease as per Lugano Criteria for Lymphoma (Cheson BD et al, 2014).

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

a. At a minimum, the 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.

b. 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.

2. 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

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. Patients with cutaneous lymphomas, mycosis fungoides (MF) or Sézary syndrome (SS).

6. Primary CNS lymphoma

7. Known symptomatic or untreated or recently treated (= 6 months of screening) central nervous system (CNS) lymphoma. Patients with previously treated ( > 6 months of screening) CNS lymphoma and are now stable and asymptomatic, from CNS perspective, are allowed

8. Patients with lymphoma that requires immediate cytoreductive therapy

9. Patients with low-grade lymphoma that does not meet conventional criteria for requiring treatment.

10. Patients on the drugs which are sensitive substrates of CYP2C8 and cannot be discontinued at least one week prior to Cycle 1 Day 1.

11. Patients on the drugs which are sensitive substrates of either Pglycoprotein (P-gp) or breast cancer resistance protein (BCRP) and cannot be discontinued at least one week prior to Cycle 1

Day 1.

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

13. 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.

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

15. Known active or chronic hepatitis B (HbsAg +ve) or hepatitis C infection (HCV antibody +ve)

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

17. 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

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

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

20. 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 (e.g. renal, hepatic, hematologic,

gastrointestinal, endocrine, pulmonary, or psychiatric illness/social situations or clinically significant laboratory / ECG

abnormalities at screening, any or a combination of illnesse

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
First cycle DLT <br/ ><br>Safety & tolerability of AUR108 as measured by NCI <br/ ><br>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, t1/2 & MRT <br/ ><br>Comparison of PK parameters in fasting & fed conditionsTimepoint: Day 28 <br/ ><br>

Secondary Outcome Measures

Name	Time	Method
PD biomarkers <br/ ><br>Efficacy assessments overall response rates, duration of <br/ ><br>response, PFS etc. as measured by Lugano Criteria for <br/ ><br>Lymphoma (Cheson BD et al, 2014)Timepoint: Day 28