A Phase 1, Open Label, Dose Escalation, Multicenter Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of Oral AUR104 in Patients With Select Relapsed/Refractory Lymphoid Malignancies (VIJAY-1)
Phase: PHASE1
Conditions: Select Relapsed/Refractory Lymphoid Malignancies
Sponsor: Aurigene Discovery Technologies Limited

Clinical Trial Protocol 
 
Protocol AUR104-101 
  
Version 3.0, 04 Jan 2024 
CLINICAL TRIAL PROTOCOL  
A Phase 1, Open Label, Dose Escalation, Multicenter Study Evaluating the 
Safety, Pharmacokinetics, and Pharmacodynamics of Oral AUR104 in 
Patients with Select Relapsed/Refractory Lymphoid Malignancies (VIJAY-
1) 
 
 
 
Confidentiality Statement 
This document is the property of Aurigene Oncology Limited (a subsidiary of Dr. Reddy's Laboratories Limited). The 
information in this document contains trade secrets and commercial information that are privileged or confidential and may 
not be disclosed without the express written permission of Aurigene Oncology Limited, unless required by federal or state 
law or regulations. Any person to whom the information is disclosed must be informed that the information is privileged or 
confidential and may not be further disclosed by them. These restrictions on disclosure will apply equally to all future 
information supplied to you that is indicated as privileged or confidential. 
 
Protocol Number  
AUR104-101 
Clinical Trial Protocol Version 
3.0 
Version date 
04 Jan 2024 
Trial Phase 
Phase 1 
Investigational Product  
AUR104 (previously known as XL-114) 
Sponsor 
Aurigene Oncology Limited 
(Subsidiary of Dr. Reddy's Laboratories 
Limited) 
39-40, KIADB Industrial Area, Phase II, 
Electronic City Hosur Road, 
Bangalore- 560100, Karnataka, India 
US IND Number 
167118 (NCT06761586) 

Clinical Trial Protocol 
 
Protocol AUR104-101 
  
Version 3.0, 04 Jan 2024 
SPONSOR SIGNATURE 
 
Study Title: 
A Phase 1, Open Label, Dose Escalation, Multicenter Study 
Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of 
Oral AUR104 in Patients with Select Relapsed/Refractory Lymphoid 
Malignancies (VIJAY-1) 
Protocol Number: 
AUR104-101 
Final Version and 
Date 
Version 3.0  dated 04 Jan 2024 
 
This study will be conducted in compliance with the clinical trial protocol approved by the 
Ethics Committee(s) (ECs) / Institutional Review Boards (IRBs) of the respective sites. The 
study will comply with the International Council for Harmonization (ICH) Good Clinical 
Practice (GCP) guidelines and current revision of the Declaration of Helsinki. In addition, this 
study will be conducted in compliance with all local regulatory and ethical requirements, US 
FDA guidelines and the New Drugs and Clinical Trials Rules, 2019 of the Department of 
Health and Family Welfare, India. The investigator will be provided with details of any 
significant or new findings, including adverse events, relating to treatment with the 
investigational product. 
 
 
____________________________________                            _________________ 
Dr. Suchit Kumbhare, MBBS, MSCR, MS  
 
 
Dated 
Senior Manager - Clinical Development                                    
 
Aurigene Oncology Limited 
(Subsidiary of Dr. Reddy’s Laboratories Limited) 
 
 

Clinical Trial Protocol 
 
Protocol AUR104-101 
  
Version 3.0, 04 Jan 2024 
PROTOCOL SIGNATURE PAGE 
Study Title: A Phase 1, Open Label, Dose Escalation, Multicenter Study Evaluating the 
Safety, Pharmacokinetics, and Pharmacodynamics of Oral AUR104 in Patients with 
Select Relapsed/Refractory Lymphoid Malignancies (VIJAY-1) 
 
I confirm that I have read, and I understand this protocol and other appropriate related 
documentation, including the Investigator’s Brochure for AUR104. I agree that the available 
nonclinical information on the investigational product is adequate to support the proposed 
clinical trial. This study will be conducted in compliance with the clinical trial protocol 
approved by the Ethics Committee (EC) / Institutional Review Board (IRB) overseeing the 
study at the site. The study will comply with the International Council for Harmonisation (ICH) 
Good Clinical Practice (GCP) guidelines and the current revision of the Declaration of Helsinki 
and all the local regulatory and ethical requirements. I will also appropriately direct and assist 
the personnel at the trial site who will be involved in the conduct of the study. 
 
Principal Investigator or Clinical Site Investigator: 
 
 
 
Signature  
 
 
 
 
 
 
 
Date 
 
Name: 
 
Title: 
 
Name of the site: 
 
 
 

Clinical Trial Protocol 
 
Protocol AUR104-101 
  
Version 3.0, 04 Jan 2024 
1.0 
SYNOPSIS   
Name of 
sponsor/com
pany: 
Aurigene Oncology Limited 
(Subsidiary of Dr. Reddy's Laboratories Limited) 
39-40, KIADB Industrial Area, Phase II, 
Electronic City, Hosur Road, 
Bangalore- 560100, Karnataka, India 
Name of 
investigation
al product: 
AUR104 (previously known as XL114) 
Name of 
active 
ingredient:  
AUR104 (previously known as XL114) 
Title of Trial:   
A Phase 1, Open Label, Dose Escalation, Multicenter Study Evaluating 
the Safety, Pharmacokinetics, and Pharmacodynamics of Oral 
AUR104 in Patients with Select Relapsed/Refractory Lymphoid 
Malignancies (VIJAY-1) 
Estimated 
Number of 
Trial 
Center(s): 
Multicenter 
Approximately 15-20 sites in Dose Escalation Cohorts 
Trial Duration 
(months):  
15-18 months  
Phase of 
development:  
1 
Objectives: 
 
Primary  
• To assess the safety and tolerability of single-agent AUR104 in 
patients with relapsed advanced lymphoid malignancies. 
• To assess the pharmacokinetics (PK) profile of AUR104. 
Exploratory 
• To explore the pharmacodynamics (PD) effects of AUR104.  
• Efficacy of AUR104 
Methodology:  
 
This is a multicenter, open-label, Phase 1 study of AUR104 in adult 
patients 
with 
select 
Relapsed/Refractory 
(R/R) 
Lymphoid 
Malignancies. 
 
The dose escalation will be conducted in a rule-based manner in 
patients who do not have any available curative treatment options and 
have exhausted all effective therapies available locally. The main 
objective of the study will be to evaluate the safety and tolerability of 
the study drug AUR104.  
 
 

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Dosing Regimen 
The starting dose level of single agent AUR104 is 20 mg once a day 
(QD). Currently, three dose levels are planned with six DLT evaluable 
patients at each dose cohort. These include 20 mg PO QD, 10 mg PO 
BID, and 15 mg PO BID. There is no increase in cumulative daily dose 
from Cohort 1 to Cohort 2 and only the dosing regimen is changed, 
from QD (20 mg QD) to BID (10 mg BID). This is primarily done to 
reduce the Cmax.  Any dosages above 15 mg BID will be presented as 
an amendment, if deemed appropriate. This will be following an overall 
assessment of safety, PK, and PD at these three dose cohorts.   
 
Additional patients may be enrolled at any of these dose cohorts to 
assess non-DLT AEs and/or PK and/or PD in greater detail, if deemed 
appropriate. 
 
Enrollment plan and Definition of DLT Evaluable 
Each Cohort will enroll six DLT evaluable patients. For Cohort 1 and 
2, a patient will be considered DLT evaluable if they successfully 
complete the first cycle of dosing (28 days) with ≥75% compliance to 
the study drug (i.e., taking the study drug for at least 21 out of 28 days). 
In Cohort 3 (and any future cohorts, after amendment), there will be a 
4-day ramp up phase. Therefore, for Cohort 3 (and future cohorts after 
amendment), a DLT evaluable patient will be one who completes 32 
days of dosing (which includes an initial 4-day ramp-up phase) with a 
compliance of 75% (i.e., taking the study drug at the assigned dose 
level for at least 21 out of last 28 days of dosing). If <75 % compliance 
is due to study drug related AE, then it will be considered a DLT. If < 
75% compliance is due to any other factor other than an AE, then the 
patient will be replaced.   
 
Rules for escalation and de-escalation 
• Within first dose cohort (20 mg QD) only, initial 3 patients will 
be dosed sequentially with at least one week gap. Thus, the 2nd 
patient in 1st cohort will start on or after Day 8 of the first patient 
in the cohort, the 3rd patient dosing will start on or after Day 8 
of the second patient in the cohort; The 4th, 5th, and 6th patient 
in Cohort 1 will start dosing on or after Day 8 of the 3rd patient.  
This sequential dosing will not be done in Cohort 2 or Cohort 3 
as in Cohort 2 the cumulative daily dosing is unchanged from 
Cohort 1 and in Cohort 3, there will be a ramp up phase of initial 
4 days in each patient. 
• Among 6 DLT-evaluable patients in each group, if 0 or 1 patient 
experiences DLT, then enrollment in the next higher dose 

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cohort may be started once the data of the previous cohort is 
reviewed by the SRC and once the SRC has confirmed that the 
enrolment in new cohort can be started.  
• Accrual will be paused after the sixth enrollment unless one or 
more patients are disqualified or are not eligible for DLT 
evaluation. 
• If 2 or more of 6 patients at a given dose level experience DLT 
during the first cycle, then maximal tolerated dose would have 
been exceeded and additional patients may be treated at a lower 
dose level.  
• If 0 or 1 of 6 patients experience DLT at a dose (and the higher 
dose led to at least 2 DLTs out of 6 patients), then this dose will 
be declared the maximal tolerated dose (MTD). In other words, 
MTD is defined as the dose at which ≤1 of 6 patients experience 
a DLT during Cycle 1 (28 days of dosing), with the next higher 
dose having at least 2 of 6 patients experiencing a DLT during 
Cycle 1 (28 days of dosing). 
• If ≤ 1 out of the six patients in Cohort 3 experience a DLT, a 
comprehensive safety, PK, and PD assessment will be 
conducted to suggest potential new dosing cohorts. If such a 
recommendation is warranted, an amendment of the protocol 
will be done and will be shared with regulators.    
• In addition to the above safety-related criteria, if mean Cmax and 
AUC0-24 cross 1500 ng/mL and/or 22,000 hr*ng/mL in Cohort 
1, respectively even if the safety limit allows (i.e., 0/6 or 1/6 
patients with DLT), then the study enrolment will be 
interrupted, and all available data (PK, PD, and safety) will be 
shared with regulators before any  dose escalation. If mean Cmax 
and AUC0-12 cross 1500 ng/mL and/or 11,000 hr*ng/mL 
respectively in Cohort 2 or Cohort 3, then the study enrolment 
will be interrupted, and all available data will be shared with 
regulators before additional enrolment.  
• If at any of these Cohorts (Cohort 1, 2 or 3), there is acceptable 
safety, PK and PD (even without reaching MTD), then also the 
dose escalation will stop and additional patients (approximately 
18 total including the initial 6 in dose escalation) will be 
enrolled at this cohort in order to assess more safety at this dose.  
 
Method of dosing  
Patients will take AUR104 orally with water at approximately the same 
time on each dosing day. Patients will not eat (but can drink water) for 
two hours before and one hour after taking the study drug.  

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For Cohorts 1 and 2, a total of 4 weeks (28 days) will be considered as 
one cycle, and Cycle 1 (first 28 days) is considered as the "DLT 
Evaluation Period." Enrollment day will be considered as Day 1 of 
Cycle 1 (C1D1). Day 29 of the study will be considered Day 1 of Cycle 
2 (C2D1). Accordingly, nomenclature will continue C3D1, C4D1, etc. 
for Cohorts 1 and 2. 
 
For Cohort 3 (15 mg BID cohort), the dosing regimen will have a ramp-
up phase for a period of 4 days. i.e., the patient will receive 10 mg BID 
for the first 4 days and will start receiving 15 mg BID from Day 5 
onwards.  For example, for patients in Cohort 3 (15 mg BID dose 
cohort), the starting dose will be 10 mg BID for 4 days, followed by a 
planned dose of 15 mg BID from C1D5 onwards.   
Therefore, the DLT evaluation period (i.e., first cycle) for Cohort 3 will 
be 32 days (including 4 days of ramp-up phase) from the day of drug 
initiation (Day 1). After that every cycle will comprise of 28 days for 
cohort 3 as well. 
If ≤ 1 out of the six patients in Cohort 3 experience DLT, a 
comprehensive safety, PK, and PD assessment will be conducted to 
suggest potential new dosing cohorts. An amendment will 
subsequently be initiated if deemed appropriate.  
Maximum Tolerated Dose 
The dose at which no more than one DLT has occurred in six patients 
and a higher dose has shown two or more DLTs, will be assessed as the 
"Maximum Tolerated Dose."  
 
Backfill cohorts may also be allowed in the trial. The Backfill cohort 
patients could only be enrolled at a dose level that the SRC has already 
reviewed, and the dose level has been deemed to be safe by the SRC. 
Backfill cohort patients may provide "Intensive PK" sampling if 
required for more PK data of respective dose levels. They might 
undergo PD sampling and sparse PK as needed. 
 
Part 2 [Single agent AUR104 dose expansion] 
Expansion cohorts in any specific lymphoid malignancy will only be 
started after an amendment. 
 
Number of 
Patients (Planned): 
• ~ 18 patients will participate in the three cohorts during the 
Dose Escalation Part.  
 

Clinical Trial Protocol 
 
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• ~  If there is adequate safety, PK and PD, then additional ~ 12 
patients (to a total of ~ 18 at the dose level) will be enrolled 
for better assessment of safety at the dose level.  
 
• Additional cohorts beyond Cohort 3 as well as dose expansion 
cohorts in any specific lymphoid malignancy will be 
introduced through an amendment. 
 
• There may also be enrollment of additional patients for 
backfill cohorts. 
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 ≥ 1000/μL (without WBC growth factor support)  
b. Platelet count: For patients with CLL ≥ 50,000/μL; For 
patients with lymphomas ≥ 75,000/μL without bone marrow 
involvement and ≥ 50,000/μL with bone marrow 
involvement. These thresholds should be qualified without 
current 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). (Cockcroft-
Gault formula for estimated creatinine clearance [eCrCl]: 
eCrCl = [140– Age] × Weight [kg] × [0.85 if Female] / [72 
× serum creatinine (mg/dL)]). 
4. Ability to swallow and retain oral medications.  
5. Histopathological diagnosis of Non-Hodgkin Lymphoma 
(NHL) or Chronic Lymphocytic Leukemia (CLL) or Hodgkin 
disease. 
Note:  
5a. The lymphoma should be either in Stage III or IV according 
to Lugano classification (Cheson et al. 2014) at screening.  

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5b. The lymphomas included in this study must fall within one 
of the following 2017 World Health Organization categories 
except lymphoma mentioned in Exclusion criterion #5: 
i. 
Mature B-cell neoplasms (excluding plasma cell 
neoplasms, heavy chain disease, and primary 
central nervous system [CNS] lymphoma). 
ii. 
Mature T- and NK-cell neoplasms. 
iii. 
Hodgkin lymphomas. 
5c. The CLL should be Binet Stage C/Rai stage III or IV, as per 
the International Workshop on Chronic Lymphocytic Leukemia 
(iwCLL) guidelines (Halek et al. 2018). 
6. In the case of patients who have lymphoid malignancies for 
which high-dose chemotherapy and autologous stem cell 
transplantation (HD-ASCT) is considered standard curative 
therapy, eligibility for this study requires that the subject's 
disease has relapsed after HD-ASCT, or the subject is not 
eligible for HD-ASCT, or the subject has refused HD-ASCT. 
7. In the case of patients who have lymphoid malignancies for 
which CAR-T therapy is indicated, eligibility for this study 
requires that the disease has relapsed after CAR-T, or the patient 
is not eligible for CAR-T, or the patient has refused CAR-T, or 
the CAR-T is not available locally. 
8. Evidence of measurable disease as per Lugano Criteria for 
Lymphoma (Cheson et al. 2014) or evidence of measurable 
disease as per iwCLL Criteria for CLL (Halek et al. 2018). 
Note: Patients with Small Lymphocytic Lymphoma (SLL) alone 
or in combination with CLL are allowed.  
9. Standard curative measures do not exist, and the patient must 
have exhausted all effective therapies available locally. At a 
minimum, the patients must have relapsed or refractory disease 
to at least 2 prior lines of systemic therapies for NHL or CLL, 
or Hodgkin’s disease. 
Note:  
• Any cancer patient with access to any effective therapy 
locally must not be enrolled. 
Exclusion Criteria  
1. Systemic anti-cancer therapy, such as chemotherapy, biological 
therapy, or immunomodulatory drug therapy, received within 
the past 28 days or 5 half-lives, whichever is longer, from Cycle 
1 Day 1 of the study.  
Note: Concomitant use of low-dose prednisone (up to 10 mg/day) 
is allowed.  

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2. Presence of acute or chronic toxicity resulting from prior anti-
cancer treatment, except for alopecia or nail changes that have 
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 Burkitt's lymphoma, Burkitt-like lymphoma, post-
transplant lymphoproliferative disease, primary mediastinal 
large-B cell lymphoma, cutaneous lymphomas, mycosis 
fungoides (MF), or Sezary syndrome (SS). 
6. 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 a CNS 
perspective, are allowed. 
7. Patients with lymphoma requiring immediate cytoreductive 
therapy. 
8. Patients with low-grade or indolent lymphoma not meeting 
conventional criteria (Jeong SH, 2022) for treatment. 
 
9. Elevated Serum cardiac Troponin I or troponin T > ULN at 
screening. 
10. Serum magnesium and calcium levels > 1.2 x ULN or < 0.8x 
LLN. 
11. Serum Potassium > 1.0x ULN or < 1.0x LLN. 
Note: Patients experiencing hypokalemia are permitted to 
undergo treatment to attain normal potassium levels during the 
screening period. 
12. Mean Heart Rate <60 at screening or Cycle 1 Day 1 (to be 
recorded at least 3 times at least 5 minutes apart) in ECG.  
13. Left ventricular ejection fraction (LVEF) < 50% as determined 
by an echocardiogram (ECHO) or Multigated Acquisition 
(MUGA) scan. 
14. QTcF (Fridericia) interval >450 ms for patients on ECG at 
screening and/or at Cycle 1 Day 1.  
15. Uncontrolled arterial hypertension defined as supine SBP of ≥ 
140 mm Hg AND/OR supine DBP ≥ 90 mmHg on stable doses 
of three or lesser different classes of antihypertensive drugs. 
Notes:  

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• Patients taking 4 or more classes of antihypertensives are 
excluded. Diuretics (such as furosemide or spironolactone) 
are considered as one class of anti-hypertensives. 
• The blood pressure has to be recorded 3 times at least 10 
minutes apart during Screening and Cycle 1 Day 1 (before 
dosing) in the supine position. Among these recordings, a 
single instance of SBP ≥140 mm Hg or DBP ≥ 90 mmHg will 
exclude the patient. Note: A patient excluded on these criteria 
can be re-screened after optimal BP management. 
16. Current or past history of heart failure (NYHA Class 2 or higher) 
17. Having a history of moderate to severe cardiovascular disease 
including 
unstable 
angina, 
myocardial 
infarction, 
cerebrovascular accident, or transient ischemic attack (TIA), 
within 1 year prior to Cycle 1 Day 1. 
18. Ongoing cardiac arrhythmias or conduction blocks. 
19. History 
of 
any 
ventricular 
arrhythmia 
including 
supraventricular or ventricular premature contractions.  
20. Patients on drugs which are sensitive substrates of CYP3A4 and 
cannot be discontinued at least one week prior to Cycle 1 Day 
1. 
21. Use of strong CYP3A4 inhibitors or inducers within 2 weeks 
prior to Cycle 1 Day 1.  
22. Concomitant use of any drug which is known to prolong QTc 
interval or use of such drugs within one week prior to Cycle 1 
Day 1. 
23. Major surgery ≤ 28 days from Cycle 1 Day 1 (major surgery is 
defined as a procedure requiring general anesthesia) 
24. Active infection requiring systemic therapy.  
Note: Prophylactic use of antibiotics is allowed. Any infection 
detected during the screening period, which is resolved 
adequately according to the investigator before Cycle 1 Day 1, 
is allowed. 
25. Known to be human immunodeficiency virus (HIV) positive or 
have an acquired immunodeficiency syndrome-related illness. 
26. Known active or chronic hepatitis B (HBsAg +ve) or hepatitis 
C infection (HCV antibody +ve). 
27. Patient expected to require any other form of antineoplastic 
therapy or targeted therapy while in the study. 
28. Uncontrolled intercurrent illness including, but not limited to, 
symptomatic congestive heart failure,  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, 

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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 patient's ability to participate in the study  
29. 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 the person(s) with 
confirmed Covid-19 infection, at screening or Cycle 1 Day 1. 
30. History of another primary malignancy within 5 years prior to 
starting the study drug, except for adequately treated basal or 
squamous cell carcinoma of the skin or cancer of the cervix in 
situ or cured early-stage (Stage 1 or 2) prostate cancer. 
31. Positive pregnancy test for women of childbearing potential 
(WOCBP) at the screening or enrolment visit 
32. 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). 
 
Test Product, Dose, 
and Mode of 
Administration: 
AUR104 is formulated as 5 and 20 mg tablets for oral 
administration.  
 
Reference Therapy:  
None 
Duration of 
Treatment:  
Each treatment cycle will be 28 days in length for Cohort 1 and 
Cohort 2.  
 
In Cohort 3, the treatment cycle 1 will be 32 days which includes 4 
days of ramp-up phase. Cycle 2 and future cycles in Cohort 3 will be 
28 days.  
 
Patients who are deriving clinical benefit (defined as not meeting 
criteria for progressive disease by Lugano Criteria for NHL/Hodgkin 
lymphoma (Cheson et al. 2014) or iwCLL criteria for CLL (Halek et 
al. 2018) may continue to receive AUR104 until either progressive 
disease or intolerable toxicity occurs. 
Endpoints: 
 
Primary Endpoints:  
• First cycle DLT  
• Safety and tolerability of AUR104 as measured by NCI 
CTCAE v 5.0.  
• PK parameters including but not limited to AUC(0-12), AUC (0-

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24), AUC0-t, Cmax, Cmin, Tmax, MRT, and t½.  
Dose-Limiting Toxicities (DLTs) 
DLT assessment will occur in the initial 28 days (Cycle 1) of treatment 
for Cohorts 1 and 2. In the case of Cohort 3, DLT evaluation will be 
done in 32 days which includes the initial 4 days of the ramp-up phase. 
Safety and tolerability will be assessed by the incidence and severity of 
adverse events as determined by NCI Common Terminology Criteria 
for Adverse Events (NCI CTCAE v 5.0). A Safety Review Committee 
(SRC) comprised of the Medical Monitor(s), Principal Investigators, 
and Sponsor representatives will review safety information and decide 
upon dose escalation and further patient enrollment. 
 
A DLT is defined as any of the following toxicities occurring during 
Cycle 1 during Part 1 (Single agent Dose Escalation Part) unless clearly 
or incontrovertibly related to the underlying malignancy, any other co-
morbidities or concomitant medications or extraneous causes: 
 
The DLTs include: 
• Decrease in Left Ventricular Ejection Fraction (LVEF) to < 
50% AND an absolute drop in LVEF by > 10%. 
      (Note: Both need to be fulfilled to be called a DLT) 
• Grade 3 or higher Left Ventricular Systolic Dysfunction. 
• Asymptomatic Systolic BP ≥160 mmHg AND/OR Diastolic 
BP ≥100 mmHg, persisting for 3 days despite optimal medical 
management.  
• Symptomatic Systolic BP ≥160 mmHg AND/OR Diastolic BP 
≥100 mmHg, regardless of duration.  
• Grade 4 hypertension. 
• Myocardial Infarction, new onset angina, Transient Ischemic 
Attack (TIA), or Stroke. 
• Asymptomatic Grade 3 or higher QTc prolongation (Average 
QTcF > 500 ms. and/or >60 ms. change from baseline).  
• Grade 2 or higher QTc prolongation (Average QTcF: 481- 500 
ms.) with cardiovascular symptoms suggestive of arrhythmia, 
such as palpitation, shortness of breath, chest pain, etc. 
Note: If the QTcF interval exceeds 480 ms. at any timepoint, the ECG 
will be repeated twice, and the average reading will be recorded. 
• Grade 3 or higher Sinus Bradycardia. 
• Grade 2 or higher Atrial Fibrillation. 
• Grade 2 or higher Atrial Flutter.  
• Grade 2 or higher Ventricular Arrhythmia. 

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• Grade 2 or higher Atrio-Ventricular Block. 
• Asymptomatic elevation of Cardiac Troponin I and/or Cardiac 
Troponin T ≥ 1.2 x ULN confirmed by two separate readings.  
• Grade 2 or higher Rhabdomyolysis. 
• Grade 2 or higher CPK elevation (2.5-5 x ULN) with Grade 2 
or higher muscle weakness, myalgia, or myopathy. 
• Asymptomatic Grade 3 or higher CPK elevation (> 5.0 x 
ULN). 
• Febrile neutropenia as per NCI CTCAE v 5.0 - ANC < 1000 
/µL with a single temperature of >38.3 degrees C (101 degrees 
F) or a sustained temperature of ≥ 38 degrees C (100.4 degrees 
F) for more than one hour 
• Grade 4 neutropenia (ANC < 500/µL). 
• Grade 3 neutropenia (ANC < 1000 - 500/μL) without fever, 
lasting at least for 7 days. 
• Grade 4 thrombocytopenia (< 25,000/µL). 
• Grade 3 thrombocytopenia (platelet count < 50000-25000/μL) 
associated with Grade 2 or higher bleeding. 
• Grade 4 anemia (life-threatening and/or with a need for urgent 
interventions) not due to underlying disease. 
• Positive for Hy's law (AST or ALT ≥ 3 x ULN with 
concomitant Total Bilirubin≥ 2 x ULN, without findings of 
cholestasis on radiological scans and no other reasons for 
increase in AST/ALT and bilirubin, such as viral hepatitis or 
acute liver disease or another drug which can clearly result into 
these findings). 
• Any other Grade 3 or higher clinically significant toxicity 
(except alopecia or nail changes), per NCI CTCAE v 5.0, which 
is considered as "not clearly or incontrovertibly related to the 
underlying 
malignancy, 
any 
other 
co-morbidities 
or 
concomitant medications or extraneous causes" by the 
investigator/SRC. 
(Asymptomatic 
Grade 
3 
electrolyte 
abnormalities are excluded from DLT definition if these 
abnormalities resolve to Grade 1 or less within 72 hours). 
• Any other AE, apart from the aforementioned DLTs, (not 
clearly or incontrovertibly related to the underlying 
malignancy, any other co-morbidities or concomitant 
medications or extraneous causes) that leads to either 
discontinuation of the study drug or leading to < 75% 
compliance during 1st cycle (i.e. < 21 out of 28 day of dosing 
in Cycle 1 in Cohorts 1 and 2  and < 21 out of last 28 day of 
dosing in Cycle 1 in Cohort 3) 

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• Any other toxicity which, in the judgment of the Safety 
Review Committee (SRC), is determined to be a DLT.   
 
Exploratory Endpoints:  
• PD biomarkers. 
• Efficacy assessments of overall response rates (ORR), 
duration of response (DOR), Progression Free Survival (PFS), 
etc., as measured by Lugano Criteria for NHL/ Hodgkin’s 
lymphoma (Cheson et al. 2014) or iwCLL criteria for CLL 
(Halek et al. 2018).  
 
Early termination or Interruption Criteria 
 
This study may be prematurely terminated, if in the opinion of the 
Sponsor there is sufficiently reasonable cause. In the event of such 
action, written notification documenting the reason for the study 
termination will be provided to each Investigator and the regulators. 
 
The study will be terminated if any of the following circumstances 
occurs:  
• Occurrence of two DLTs at any dose level, without adequate 
PK exposure where de-escalation is not meaningful for further 
drug development. 
• Determination of unexpected, significant, or unacceptable risk 
to subjects. 
• Slow recruitment. 
• Plans to modify, suspend, or discontinue the development of 
the study treatment. 
• Decisions of regulatory authorities or IRB/IEC. 
 
Enrolment in the study will be interrupted and engagement with 
regulators will immediately occur, if any of the following events 
(irrespective of the cycle) occur at any time (during or beyond the 
DLT evaluation period): 
• Any case of life-threatening or fatal cardiovascular toxicity, 
e.g., malignant hypertension, unstable angina, myocardial 
infarction, stroke, TIA (transient ischemic attack), ventricular 
arrhythmia, etc.  
• Any case of life-threatening or fatal rhabdomyolysis 
• Any other case of life-threatening or fatal event, which is not 
clearly or incontrovertibly related to the underlying 

Clinical Trial Protocol 
 
Protocol AUR104-101 
  
Version 3.0, 04 Jan 2024 
malignancy, any other co-morbidities or concomitant 
medications or extraneous causes. 
• If mean Cmax and AUC0-24 cross 1500 ng/mL and/or 22,000 
hr*ng/mL respectively at any QD dosing cohort. In the case of 
BID dosing, if mean Cmax and AUC0-12 cross 1500 ng/mL 
and/or 11,000 hr*ng/mL respectively.  
 
In addition to above “Interruption Criterion” for the study, if there 
are non-life threatening cardiovascular / muscular DLT 
equivalents in patients, in the post- DLT period, then dosing in 
those patients will be stopped and all the safety data will be 
thoroughly evaluated as a whole. If such non-life threatening DLT 
equivalents (for cardiovascular and/or muscular toxicity) are 
occurring in more than 20% of patients at any specific dose or 
across dosages, then a report will be prepared and presented to the 
agency, for discussion if the study should be stopped or continued.  
If a DLT or DLT equivalent (cardiovascular and/or muscular 
toxicities) AEs are observed in over 30% of patients at a particular 
dose level or across multiple doses over any treatment duration, 
then the enrollment in the study will be halted. A comprehensive 
safety report will be prepared and presented to regulators to guide 
the decision-making process for the next steps for the trial. 
 Statistical Analysis: 
 
General: 
Descriptive statistics will be used.  
Safety Analyses: 
Safety observations and measurements include drug exposure, AEs, 
safety laboratory tests, vital signs, physical examinations, ECGs, 
echocardiograms, cardiac biomarkers, muscle biomarkers, and ECOG 
performance status. Adverse events will be coded using the Medical 
Dictionary for Regulatory Activities (MedDRA™) dictionary. The 
number and percentages of patients experiencing AEs will be tabulated 
by system organ class (SOC), preferred term, maximum severity, and 
relationship to AUR104. The severity of AEs will be graded according 
to the NCI CTCAE v 5.0. Summaries of the number of patients with 
dose 
reductions/interruptions, 
SAEs, 
AEs 
resulting 
in 
trial 
discontinuation, and deaths will be presented by dose, tumor type, and 
overall. Laboratory parameters will be summarized using descriptive 
statistics by post-dosing shifts in NCI CTCAE toxicity grade relative 
to baseline and data listings of clinically significant abnormalities. 
Vital signs and ECG data will be summarized by changes from baseline 
values using descriptive statistics (number of patients, mean, median, 
standard deviation, minimum, and maximum), and physical 
examination abnormalities and ECOG performance status will be 

Clinical Trial Protocol 
 
Protocol AUR104-101 
  
Version 3.0, 04 Jan 2024 
summarized using frequencies and percentages. 
 
Efficacy Analyses: 
Patients will be assessed by radiological scans by Lugano Criteria for 
NHL/ Hodgkin’s lymphoma (Cheson et al. 2014) or iwCLL criteria for 
CLL (Halek et al. 2018).  
 
Objective tumor response rates (ORR), duration of response (DOR), 
time to objective tumor response, time to progression (TTP), and 
progression free survival (PFS) will be presented. Additionally, tumor 
lesion measurements and changes from baseline will be summarized 
by cycle, tumor type, and dose. Tumor markers will also be 
summarized by cycles.   
 
Pharmacokinetic Analyses:   
Individual plasma PK parameters, including but not limited to AUC (0-
12), AUC (0-24), AUC0-t, Cmax, Tmax, Mean Residence Time (MRT), and 
t½, will be estimated using appropriate compartmental or non-
compartmental models. Summaries of PK parameters will be presented 
by dose groups and tumor histology.  
  
Exploratory Biomarkers: Summaries of PD biomarkers will be 
presented by dose groups.