Clinical trial NCT05021900
Conditions: Locally Advanced Breast Cancer Metastatic Breast Cancer
Keywords: RP6530 Tenalisib
Sponsor: Rhizen Pharmaceuticals SA
Start date: 2021-10-13; Completion date: 2023-03-31
Enrollment: 40 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Phase II, randomized, open-label study, designed to evaluate the preliminary efficacy and safety of tenalisib at two dose levels in 40 patients with locally advanced or metastatic breast cancer.

Detailed description:
The study will have two groups, Group 1 with a treatment option of 800mg RP6530 BID and Group 2 with a treatment option of 1200mg RP6530 BID, where the subjects will be randomly assigned to each group in 1:1 and continued on each group of treatment till disease progressed.

Arms: arm 1: Single agent at a dose of 800 mg BID arm 2: Single agent at a dose of 1200 mg BID
Interventions: intervention 1: Tenalisib 800mg intervention 2: Tenalisib 1200mg
Intervention descriptions: intervention 1: Tenalisib will be administered 800mg BID, orally intervention 2: Tenalisib will be administered 1200mg BID, orally

Protocol documents:
Prot_000.pdf: 
CONFIDENTIAL 
Page 1 of 66 
   
                                               
 
 
PROTOCOL NO. RP6530-2101 
 
A Phase II, Multi-center, Randomized, Open label, two arm Study to Assess 
the Efficacy and Safety of Tenalisib (RP6530), a PI3K δ/γ and SIK3 Inhibitor, 
in patients with Locally Advanced or Metastatic Breast Cancer 
 
 
 
 
 
 
This document is a confidential communication of Rhizen Pharmaceuticals. Acceptance of this document 
constitutes agreement by the recipient that no unpublished information contained herein shall be 
published or disclosed without prior written approval.
PROTOCOL NUMBER 
RP6530-2101 
TRIAL DRUG 
Tenalisib (RP6530) 
 
 
SPONSOR 
Rhizen Pharmaceuticals AG 
Steinentorstrasse 23,  
4051 Basel,  
Switzerland 
 
 
SPONSOR’S MEDICAL 
EXPERT 
Prajak Barde, MD 
Sr. Medical Director, Clinical R&D  
Rhizen Pharmaceuticals AG 
Steinentorstrasse 23,  
4051 Basel,  
Switzerland 
 
 
DOCUMENT VERSION 
Version 1.0, Dated June 29, 2021  


Protocol No. RP6530-2101 
                                                     Rhizen Pharmaceuticals AG 
Version 1.0, Dated June 29, 2021 
CONFIDENTIAL 
Page 2 of 66 
Clinical Trial Protocol Statement of Compliance 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
This clinical trial shall be conducted in compliance with the protocol, as referenced herein, 
and all applicable local, national, and international regulatory requirements to include, but 
not be limited to: 
 
 
• 
International Conference on Harmonization (ICH) Guidelines on Good Clinical 
Practice (GCP) 
• 
Ethical principles that have their origins in the Declaration of Helsinki  
• 
European Commission - Detailed guidance on the collection, verification and 
presentation of adverse event/reaction reports arising from clinical trials on medicinal 
products for human use (‘CT-3’) (2011/C 172/01) 
• 
As the principal investigator (PI), I understand that my signature on the protocol 
constitutes my agreement and understanding of PI responsibilities to conduct the clinical 
trial in accordance to the protocol and applicable regulations. Furthermore, it constitutes 
my understanding and agreement that any changes initiated by myself, without prior 
agreement in writing from the Sponsor, shall be defined as a deviation from the protocol, 
and shall be formally documented as such. 
• 
As the Clinical Research Organization (CRO) Representative, I agree and accept the 
contracted sponsor responsibilities as defined by the protocol, applicable clinical trial 
agreements (CTA), and/or business contracts.  Additionally, I agree that any changes to 
the protocol, CTA, or contracts shall be implemented with the Sponsor’s review and 
approval prior to implementation.  
• 
As the Sponsor Representative, I understand that my signature constitutes agreement and 
understanding of acceptance of the defined and contracted sponsor responsibilities to the 
CRO as defined by the protocol, applicable clinical trial agreements (CTA), and/or 
business contracts, but does not in any capacity relieve me of my responsibilities as the 
Sponsor.  Additionally, my signature constitutes my understanding and agreement that 
any changes to the protocol, CTA, or contracts shall be implemented timely with my 
review and approval prior to implementation. 
 


Protocol No. RP6530-2101 
                                                     Rhizen Pharmaceuticals AG 
Version 1.0, Dated June 29, 2021 
CONFIDENTIAL 
Page 3 of 66 
Protocol Approval Page 
 
A Phase II, Multi-center, Randomized, Open label, two arm Study to Assess 
the Efficacy and Safety of Tenalisib (RP6530), a PI3K δ/γ and SIK3 Inhibitor, 
in patients with Locally Advanced or Metastatic Breast Cancer 
 
PROTOCOL NUMBER 
RP6530-2101 
TRIAL DRUG(S) 
Tenalisib (RP6530) 
DOCUMENT VERSION 
Version 1.0, Dated Jun 29, 2021 
             
 
 
 
Prajak Barde, MD 
 
 
 
 
                                                
______________________________________________________ 
 
 
________________________________________________________________________ 
Sponsor’s Medical Expert   
 
 
Signature  
 
 
Date 
 
 
 
 
 
 
 
Ajit Nair, PhD  
  
 
______________________________________________________ 
 
 
________________________________________________________________________ 
Sponsor’s Representative   
 
 
Signature 
 
 
Date             
 
 
 
 
 
 
Michael Chen, PhD 
 
 
 
 
                                                 
______________________________________________________ 
 
 
_______________________________________________________________________  
Bio-statistician 
 
 
 
 
Signature 
 
 
Date             
 
                                     
 
 
 
 
 
 


Protocol No. RP6530-2101 
                                                     Rhizen Pharmaceuticals AG 
Version 1.0, Dated June 29, 2021 
CONFIDENTIAL 
Page 4 of 66 
 
Protocol Acceptance Page 
 
A Phase II, Multi-center, Randomized, Open label, two arm Study to Assess 
the Efficacy and Safety of Tenalisib (RP6530), a PI3K δ/γ and SIK3 Inhibitor, 
in patients with Locally Advanced or Metastatic Breast Cancer 
 
PROTOCOL NUMBER 
RP6530-2101 
TRIAL DRUG(S) 
Tenalisib (RP6530) 
DOCUMENT VERSION 
Version 1.0, Dated June 29, 2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Principal Investigator 
 Signature 
 
         Date       
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 


Protocol No. RP6530-2101 
                                                     Rhizen Pharmaceuticals AG 
Version 1.0, Dated June 29, 2021 
CONFIDENTIAL 
Page 5 of 66 
PROTOCOL SYNOPSIS 
Study Title 
A Phase II, Multi-center, Randomized, Open label, two arm Study to Assess the 
Efficacy and Safety of Tenalisib (RP6530), a PI3K δ/γ and SIK3 Inhibitor, in patients 
with Locally Advanced or Metastatic Breast Cancer 
Phase 
Phase II 
Study Sponsor 
Rhizen Pharmaceuticals AG 
Study Centers  
Approximately 05 study centers in Georgia 
Study Objectives 
Primary Objective 
• 
To assess the anti-tumour activity of tenalisib in patients with locally advanced 
or metastatic breast cancer    
 
Secondary Objective 
• 
To evaluate the safety and tolerability of tenalisib  
 
Exploratory Objectives 
• 
Changes in serum cytokines/chemokines and tumour tissue gene expression 
post treatment with tenalisib.  
 
Endpoints 
Primary Endpoint 
• 
Percentage of patients without disease progression at the end of 6 months. 
 
Secondary Endpoints 
• 
Overall Response Rate (ORR), Clinical Benefit Rate (CBR) and Progression Free 
Survival (PFS). 
• 
Adverse Event (AE), Grade 3/4 AEs, Serious Adverse Event (SAE) evaluated 
and graded using NCI-CTCAE Version 5.0. 
 
Exploratory Endpoints 
• 
Change from baseline in cytokine/chemokine levels post treatment with tenalisib  
• 
Change in gene expression profiles as measured by RNA sequencing from 
tumour biopsy samples post treatment with tenalisib.  
Study Design  
This is a Phase II, randomized, open label study, designed to evaluate the preliminary 
efficacy and safety of tenalisib at two dose levels (800 mg BID and 1200 mg BID) in 
40 patients with locally advanced or metastatic breast cancer. 20 patients each, will 
be enrolled in Group 1 (Tenalisib 800 mg BID) and Group 2 (Tenalisib 1200 mg 
BID). Both groups will be run in parallel.   
Study Procedure 
The study treatment will be administered orally in 28 days of cycle until disease 
progression or unacceptable toxicity for a maximum duration of 24 months. The 
detailed study procedure is presented in Study assessment and Treatment schedule 
(Table 5). Safety including laboratory assessments and electrocardiogram (ECG), 
and radiological assessments including CT and/or MRI will be performed at the 
protocol specified timepoints at the respective sites. 
No. of Patients 
40 patients (20 patients per group) will be enrolled in two parallel groups.   
Estimated Study 
Participation  
The subject will participate in the study until disease progression, consent 
withdrawal or unacceptable toxicity for a maximum duration of 24 months. 


Protocol No. RP6530-2101 
                                                     Rhizen Pharmaceuticals AG 
Version 1.0, Dated June 29, 2021 
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Page 6 of 66 
Inclusion 
Criteria 
Individuals should meet all the following criteria to be considered eligible to 
participate in the study:  
1. Provision of full informed consent prior to any study-specific procedures.  
2. Patients must be ≥18 years of age, at the time of signing informed consent. 
3. Female patients who have histologically and/or cytologically confirmed locally 
advanced or metastatic breast cancer that has progressed following at least one 
line of therapy.  
4. Patients with at least one measurable lesion per RECIST version 1.1 at baseline 
that can be accurately assessed by CT scan or MRI and is suitable for repeated 
assessment at follow up-visits.   
5. ECOG performance status 0 to 2.  
6. Life expectancy of at least 3 months. 
7. Adequate bone marrow, liver and renal functions as assessed within 7 (±2) days 
before the first dose of study drug with the following laboratory requirements: 
a. Hemoglobin ≥ 8.0 g/dL (should not be transfused or treated with 
erythropoietin to maintain or exceed this level) 
b. Absolute neutrophil count (ANC) ≥ 1.0 x 109/L without growth factor 
support 
c. Platelet count ≥ 75 x 109/L 
d. Total bilirubin ≤ 1.5 times the ULN (or ≤ 3 x ULN, if the patient has Gilbert 
syndrome)  
e. ALT and AST ≤ 3 x ULN (≤ 5 x ULN for patients with liver metastasis or 
liver involvement)  
f. Creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault 
formula) for patients with creatinine levels above ULN. 
8. Female patient of childbearing potential should be willing to use a medically 
acceptable method of contraception as defined in Appendix B while participating 
in the study and for 30 days after the last dose of study drug AND must have a 
negative serum pregnancy test within 3 days prior to Cycle 1 Day 1 (C1D1). 
9. Ability to swallow and retain oral medication. 
10. Willingness and capability to comply with the study requirements.  
Exclusion 
Criteria 
Individuals who meet any of the following criteria will be considered ineligible to 
participate in the study:  
1. Patients with HER-2 positive breast cancer. 
2. Patients receiving anticancer therapy (e.g., chemotherapy, biologic therapy, 
hormonal therapy or any other investigational product) within 4 weeks or 5 half-
lives of the drug prior to C1D1, whichever is shorter. Treatment interval will be 
6 weeks for nitrosoureas or mitomycin C.  
3. Patient who has not recovered from acute toxicities (defined as NCI-CTCAE 
grade > 1) of previous therapy except treatment-related alopecia. (Note: Patient 
with any unresolved toxicities which in the opinion of PI are stable and controlled 
with medication can be enrolled in the study).  
4. Patients who have had disease progression within 8 weeks of platinum 
chemotherapy. (Note: Patients who have had a disease-free interval of more than 
8 weeks following platinum chemotherapy; and patients with previous 
neoadjuvant OR adjuvant platinum-based therapy can participate in the study). 
5. Prior exposure to investigational or marketed PI3K inhibitors (e.g., idelalisib, 
copanlisib, duvelisib, umbralisib, alpelisib, buparlisib) given for the treatment of 
breast cancer. 
6. Major surgery within 4 weeks of starting study treatment OR any patient who has 
not recovered from the effects of major surgery.  


Protocol No. RP6530-2101 
                                                     Rhizen Pharmaceuticals AG 
Version 1.0, Dated June 29, 2021 
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7. Patient with symptomatic uncontrolled brain metastasis. (Note: A scan to confirm 
the absence of brain metastases is not required. Patients whose brain metastatic 
disease has remained stable for ≥ 4 weeks (prior to the start of study treatment) 
following treatment of brain metastases are eligible. The patient can receive a 
stable dose of corticosteroids before and during the study if steroids were started 
at least 4 weeks prior to C1D1). 
8. HIV positive patients who are on antiretroviral therapy OR active hepatitis C OR 
active hepatitis B virus infections. 
9. Ongoing immunosuppressive therapy including systemic corticosteroids except 
as allowed per concomitant medication.  
10. Known history of severe liver injury (e.g., alcoholic liver disease, primary biliary 
cirrhosis, ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver 
or portal hypertension) as judged by investigator. (Note: Exception will be the 
patients with liver metastasis who can be enrolled in the study). 
11. History of severe cutaneous reactions (e.g., Drug Rash with Eosinophilia and 
Systemic Symptoms (DRESS), Stevens–Johnson syndrome (SJS) or toxic 
epidermal necrolysis (TEN) in the past. 
12. Active gastrointestinal tract disease with malabsorption syndrome or 
uncontrolled inflammatory gastrointestinal disease such as Crohn’s disease or 
ulcerative colitis. 
13. Myocardial infarction within 6 months before starting therapy, symptomatic 
congestive heart failure (New York Heart Association > Class II), unstable 
angina, or unstable cardiac arrhythmia requiring medication or clinically relevant 
findings in the ECG such as second-or third-degree AV block, significant 
prolongation of the QTcF interval, unless agreed between the investigator and the 
medical monitor.   
14. Concurrent disease or condition that would interfere with study participation or 
safety, such as the following:  
o Active, clinically significant infection requiring parenteral antimicrobial 
agent.   
o Clinically significant bleeding diathesis or coagulopathy, including known 
platelet function disorder.  
o Mood disorders like OCD, severe depression, history of suicidal attempt, 
schizophrenia etc. as per the investigator’s discretion. 
15. Concurrent medications or substances with the potential to affect the activity or 
pharmacokinetics of tenalisib, as reviewed and confirmed by medical monitor. 
16. Pregnancy or lactation.   
17. Patient with other active malignancies at the time of screening except for 
adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of 
breast, basal cell carcinoma of the skin or localized squamous cell carcinoma of 
the skin. (Note: Patients with prior malignancies which are treated and are in 
remission without requiring active treatment are allowed in the study.)  
18. A serious uncontrolled medical disorder or active infection which would impair 
the ability of the patient to receive protocol therapy or whose control may be 
jeopardized by the complications of this therapy. 
Note: Post eligibility confirmation, tumour biopsy will be performed in approximately 
10-12 patients who have consented for biopsy, prior to the first dose on C1D1. Eligible 
patients who do not consent for biopsy will also be enrolled into the study. Blood will be 
collected in all patients for cytokine/chemokine analysis.  


Protocol No. RP6530-2101 
                                                     Rhizen Pharmaceuticals AG 
Version 1.0, Dated June 29, 2021 
CONFIDENTIAL 
Page 8 of 66 
Administration 
of Tenalisib 
Tenalisib will be administered orally daily in 28-day cycle (Day 1-28). Tenalisib 
tablets will be self-administered orally twice daily one hour before a major meal (e.g., 
breakfast and dinner). Patients should not consume food during this one-hour period.  
If a dose of tenalisib is missed, it should be taken as soon as possible on the same day 
with an interval of minimum 8 hours between two doses. If it is missed for the entire 
day, it should not be repeated. If vomiting occurs, no attempt should be made to 
replace the vomited dose. 
Concomitant 
Medications 
In general, any concomitant medications should be avoided during study, unless it is 
required as a standard of care (necessary supportive care), prophylaxis or for the 
treatment of adverse event in the opinion of the treating investigator. Below 
recommendations should be followed, and concomitant medication should be clearly 
documented.  
1. Antimicrobial and/or anti-viral prophylaxis should be used according to local 
standard/institutional practice; Pneumocystis jirovecii pneumonia (PJP) and 
herpes zoster prophylaxis is strongly recommended. Similarly, chronic carriers 
of HBV should receive prophylactic anti-viral therapy.  
2. Hematopoietic growth factors (e.g., erythropoietin, GM-CSF and G-CSF) can be 
used for the management of acute toxicities such as febrile neutropenia when 
clinically indicated or at the discretion of the investigator.   
3. Prophylactic anti-emetic treatment is discouraged at the start of study treatment; 
however, patients can receive appropriate anti-emetic treatment at the first onset 
of nausea or vomiting and as required thereafter, in accordance with local 
standard/institutional practice.  
4. Transfusions may be given, based on standard criteria and clinical judgment.  
5. Corticosteroids are allowed for the symptomatic control of brain metastases 
provided the dose is stable before and during the study and they are started at 
least 4 weeks prior to the start of study treatment.  
6. Bisphosphonates (e.g., zoledronic acid and pamidronate) and monoclonal 
antibody denosumab are allowed for bone metastases/bone pain.  
7. Concurrent palliative radiotherapy for pain relief is allowed at the site of bone 
metastases that were present at baseline, provided the investigator does not feel 
that these are indicative of clinical disease progression during the study period; 
and radiotherapy is limited to an area other than the sole site of measurable or 
evaluable disease. Study treatment should be discontinued for a minimum of 3 
days before a patient undergoes palliative radiation.  
8. If concomitant treatment of drugs metabolized by CYP3A4/CYP2C9 enzymes 
are clinically warranted, careful observation of the patient is advised.  
9. Low molecular weight heparin (LMWH) and Direct Oral Anticoagulant (DOA) 
such as dabigatran and edoxaban are acceptable for prophylaxis and/or treatment 
of venous thrombosis. Careful observation of the patient is advised while using 
apixaban and rivaroxaban.   
10. Any Covid-19 vaccine (e.g., mRNA, viral vector and inactivated vaccine), and 
other inactivated vaccines are allowed and can be given as per the institutional 
guidance.  
11. Any other treatment (except anti-cancer therapy as mentioned in the prohibited 
medication) which is required as a part of standard of care of the institution. 
However, this should be discussed with Medical Monitor and documented.  


Protocol No. RP6530-2101 
                                                     Rhizen Pharmaceuticals AG 
Version 1.0, Dated June 29, 2021 
CONFIDENTIAL 
Page 9 of 66 
Prohibited 
medication 
The following treatments are prohibited while on the clinical trial:   
• 
Any other anti-cancer therapy (e.g., radiation therapy, hormonal, 
immunotherapy or biologic therapy). 
• 
Strong inhibitors or inducers of CYP3A4. Patients should stop using these 
medications at least 48 hrs or 5 half-lives (whichever is shorter) prior to C1D1.  
• 
Strong inhibitors or inducers of CYP2C9. Patients should stop using these 
medications at least 48 hrs or 5 half-lives (whichever is shorter) prior to C1D1. 
• 
Substrates of CYP3A4 enzyme with a narrow therapeutic range. Patients should 
stop using these medications at least 48 hrs or 5 half-lives (whichever is shorter) 
prior to C1D1.    
• 
Use of heparin and warfarin for prophylaxis and/or treatment of venous 
thrombosis is prohibited. These drugs should be stopped at least 48 hrs prior to 
C1D1.    
• 
Herbal or alternative medicines are not allowed throughout the trial. Patients 
should stop using these medications at least 48 hrs prior to C1D1.  
• 
Live attenuated vaccine (e.g., Flu vaccine, pneumovax, varicella) should not be 
administered whilst the patient is receiving study treatment. 
• 
Concurrent medications or substances with the potential to affect the activity of 
tenalisib as reviewed and confirmed by medical monitor. 
• 
Any other investigational agent. 
Discontinuation 
Criteria 
The patient will be discontinued from the study if any adverse event or procedure 
poses increased risk to the patient or interferes with the study conduct; examples 
include but are not limited to the following:  
- 
NCI CTCAE v5.0 Grade 3/4 non-hematological toxicity related to study drug 
that necessitates withdrawal in the opinion of investigator. 
- 
Development of an intercurrent illness, condition, or procedural complication, 
which could interfere with the patient’s continued participation.  
- 
Any other situation where in the opinion of the investigator, continued 
participation in the study would not be in the best interest of the patient.  
 
 
In addition, patients will be discontinued from the study in the following 
circumstances: 
- 
Consent withdrawal by the patient (all patients are free to withdraw from 
participation in this study at any time, for any reasons, specified or unspecified, 
and without prejudice). 
- 
Pregnancy  
- 
Non-compliance by study patient.  
- 
Confirmed disease progression during therapy.  
- 
Discontinuation of the study by the Sponsor 
Safety 
assessment:  
 
AEs will be recorded and graded according to National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI-CTCAE version 5.0). Physical 
examination, vital signs, ECGs and clinical laboratory tests will be performed at 
screening and at specific time points during the study. Clinical and laboratory 
evidence of AEs will be monitored routinely throughout the study and for 30 days 
following discontinuation of the study drug. 


Protocol No. RP6530-2101 
                                                     Rhizen Pharmaceuticals AG 
Version 1.0, Dated June 29, 2021 
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Efficacy 
Assessment  
• 
Computed tomography (CT) with IV contrast will be the primary modality for 
assessment, unless the patient has an allergy to contrast that cannot be controlled 
with pre-medications. If patients are unable to receive iodinated CT contrast, the 
preferred imaging is non-contrast CT of the chest, and MRI of the abdomen and 
pelvis with contrast. 
• 
Disease will be re-assessed by the site investigator/radiologist using RECIST 
version 1.1 at C3D1 (± 7 days) and approximately 8 weeks thereafter (± 7 days), 
and/or at the EOT and/or as clinically indicated (if clinical progression is 
suspected). Investigator-assessed response will be used for analysis. 
Sample 
size 
calculation: 
A sample size of 20 per group will provide a precision of 13% for a two-sided 90% 
confidence interval based on Exact (Clopper-Pearson) method assuming the 
percentage of patients without progression at the end of 6 months is 20%. Thus, a 
total of 40 patients (20 patients in each group) will be enrolled in the study.  
Statistical 
analysis:  
 
Statistical methods to analyze efficacy and safety will be described in statistical 
analysis plan (SAP). These methods may be revised and updated due to reasons such 
as regulatory requirements or need for further clarifications. The final analysis plan 
will be documented in a formal SAP that will be finalized before database lock. The 
SAP will include details on how variables will be derived, how missing data will be 
handled, and how data will be presented as well as the details on statistical methods 
to be used for safety and efficacy analyses. The final clinical study report will discuss 
deviations from the SAP, if any. 
 
The following two analysis populations are planned for this study:  
• Intent-to-Treat Population (ITT): The ITT is the primary analysis population and 
will include data from patients who have received at least 1 dose of study 
medication.  
• Per-Protocol (PP) Population: The PP Population is a subset of the ITT population 
and will include patients without major protocol deviations.  
 
Membership in the analysis populations will be determined before database lock. 


Protocol No. RP6530-2101 
                                                     Rhizen Pharmaceuticals AG 
Version 1.0, Dated June 29, 2021 
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Page 11 of 66 
                                               GENERAL INFORMATION 
SPONSOR 
Rhizen Pharmaceuticals AG 
Steinentorstrasse 23,  
4051 Basel, Switzerland  
Tel: +41 32 580 0113 
Fax: +41 32 967 9596 
SPONSOR’S 
REPRESENTATIVE 
Ajit Nair, PhD 
Chief Development Officer   
Rhizen Pharmaceuticals AG 
Steinentorstrasse 23,  
4051 Basel, Switzerland  
Tel: +41 32 580 0113 
Tel: +91 98205 03970 
SPONSOR’S MEDICAL 
EXPERT  
Prajak Barde, MD 
Sr. Medical Director, Clinical R&D  
Rhizen Pharmaceuticals AG 
Steinentorstrasse 23,  
4051 Basel, Switzerland  
Tel: +41 32 580 0175 
Tel: +91 99665 77785 
STATISTICIAN   
Michael Chen, PhD 
Consulting Statistician,  
Tel: +1-908 500 9334 
 
 
 
 


Protocol No. RP6530-2101 
                                                     Rhizen Pharmaceuticals AG 
Version 1.0, Dated June 29, 2021 
CONFIDENTIAL 
Page 12 of 66 
List of Abbreviations 
AE 
Adverse Event 
AI 
Aromatase Inhibitor 
ALP 
Alkaline Phosphatase 
ALT (SGOT) Alanine aminotransferase 
ANC 
Absolute Neutrophil Count 
AST (SGPT) 
Aspartate aminotransferase 
AUC0-t 
Area Under the plasma-concentration time curve from zero up to the last 
measurable concentration 
BID 
BRCA 
Twice Daily 
Breast Cancer gene 
β-HCG 
β-human chorionic gonadotropin 
Cmax 
Peak Drug Concentration 
CBC 
CBR 
CDK 
CLL 
Complete Blood Count 
Clinical Benefit Rate 
Cyclin Dependent Kinase 
Chronic Lymphocytic Leukemia 
CR 
Complete Response 
CT 
Computed Tomography 
CTCAE 
CTCL 
Common Terminology Criteria for Adverse Events 
Cutaneous T-cell lymphoma 
DSB 
Double Strand Break 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
ECOG PS 
Eastern Cooperative Oncology Group Performance Status 
EOS 
End of Study 
EOT 
End of Treatment 
GCP 
Good Clinical Practices 
GGT 
Gamma Glutamyl Transferase  
G-CSF 
Granulocyte Colony-Stimulating Factor 
Hb 
Hemoglobin 
HBV 
Hepatitis B Virus 
HCV 
Hepatitis C Virus 
HDPE 
High-density Polyethylene 
HIV 
HL 
HR 
Human Immunodeficiency Virus 
Hodgkin’s Lymphoma 
Homologous Recombinant 
IB 
Investigator’s Brochure  
ICF 
Informed Consent Form 
ITT 
Intent-to-Treat 
IEC 
Independent Ethics Committee 
INR 
International Normalized Ratio 
IRB/IEC 
Institutional Review Board/Independent Ethics Committee 
IUD 
Intrauterine Device 
IUS 
Intrauterine System 


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LAR 
LAR Legally Acceptable Representative 
LDH 
Lactate Dehydrogenase 
LLN 
Lower Limit of Normal  
LMWH 
Low Molecular Weight Heparin 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
Magnetic Resonance Imaging  
MTD 
Maximum Tolerated Dose 
NCI 
iNHL 
National Cancer Institute 
Indolent Non-Hodgkin’s Lymphoma 
NOAEL 
No-Observed-Adverse Effect Level 
NSAID 
Non-Steroidal Anti-Inflammatory Drug 
ORR 
Overall Response Rate 
PD 
Progressive Disease 
PARP 
Poly-ADP Ribose polymerase 
PET 
PFS 
Positron Emission Tomography 
Progression Free Survival 
PI 
PI3K 
PJP 
Principle Investigator 
Phosphoinositide 3-kinase 
Pneumocystis Jirovecii Pneumonia 
PK 
Pharmacokinetics 
PP 
Per-Protocol 
PR 
PTCL 
PTEN 
Partial Response 
Peripheral T-cell lymphoma 
Phosphatase and Tensin Homolog  
QA 
Quality Assurance 
QTcF 
Frederica’s (QTcF)  
SAE 
Serious Adverse Events 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis Software 
SD 
Stable Disease  
SDV 
SIK 
Source Document Verification 
Salt-inducible Kinase 
SOP 
Standard Operating Procedures 
t1/2 
Plasma Half Life 
TG 
TCL 
Triglyceride 
T-cell lymphoma 
TGI 
Tumour Growth Inhibition 
ULN 
Upper Limit of Normal 
UV 
Ultra-violet 
WBC 
White Blood Cells 


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TABLE OF CONTENTS  
1 
Background Information ...................................................................................................... 17 
1.1 
Background ................................................................................................................ 17 
1.2 
Tenalisib (RP6530) .................................................................................................... 18 
1.3 
Pre-clinical Studies with RP6530 .............................................................................. 19 
1.4 
Clinical Experience .................................................................................................... 19 
1.5 
Rationale .................................................................................................................... 21 
1.5.1 Study Rationale ................................................................................................ 21 
1.5.2 Rationale for Dose Selection ............................................................................ 22 
1.6 
Benefit and Risks of participation in the study .......................................................... 23 
2 
TRIAL OBJECTIVES ......................................................................................................... 24 
2.1 
Primary Objective ...................................................................................................... 24 
2.2 
Secondary Objective .................................................................................................. 24 
2.3 
Exploratory Objective ................................................................................................ 24 
3 
TRIAL DESIGN .................................................................................................................. 24 
3.1 
Trial End Points ......................................................................................................... 24 
3.1.1 Primary Endpoint .............................................................................................. 24 
3.1.2 Secondary Endpoints ........................................................................................ 24 
3.1.3 Exploratory Endpoints ...................................................................................... 24 
3.2 
Design of Trial ........................................................................................................... 24 
3.3 
Randomization ........................................................................................................... 25 
3.4 
Investigational Medicinal Product ............................................................................. 25 
3.4.1 Dosage Form and Strengths .............................................................................. 25 
3.4.2 Labeling, Packaging and Supply ...................................................................... 25 
3.4.3 Guidelines for administration of Tenalisib ....................................................... 26 
3.4.4 Accountability of Investigational Medicinal Products ..................................... 26 
3.4.5 Precautions and Risks Associated with Investigational Product ...................... 26 
3.5 
The Expected Duration of Patient Participation and Follow-up ................................ 27 
3.6 
Study Stopping Rules ................................................................................................. 27 
4 
SELECTION AND WITHDRAWAL of PATIENTS ......................................................... 27 
4.1 
Inclusion Criteria........................................................................................................ 27 
4.2 
Exclusion Criteria ...................................................................................................... 28 
4.3 
Discontinuation from Trial Treatment ....................................................................... 29 
5 
TREATMENT OF PATIENTS ........................................................................................... 30 
5.1 
Administration of Tenalisib ....................................................................................... 30 
5.2 
Concomitant Medications .......................................................................................... 30 
5.3 
Prohibited Medications .............................................................................................. 31 
5.4 
Procedures for Monitoring Patient Compliance......................................................... 32 
6 
TRIAL ASSESSMENT AND PROCEDURE ..................................................................... 32 
6.1 
Overview .................................................................................................................... 32 
6.2 
Informed Consent ....................................................................................................... 32 
6.3 
Screening .................................................................................................................... 33 
6.3.1 Assignment of screening and randomization numbers ..................................... 33 
6.3.2 Medical history ................................................................................................. 34 
6.3.3 Prior and Concomitant Medication Review ..................................................... 34 
6.3.4 Physical Examination ....................................................................................... 34 
6.3.5 Vital Signs ........................................................................................................ 35 


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6.4 
Laboratory Investigations .......................................................................................... 35 
6.5 
12-Lead Electrocardiograms ...................................................................................... 36 
6.6 
Tumour Biopsy .......................................................................................................... 36 
6.7 
Serum Cytokines/Chemokines ................................................................................... 36 
6.8 
End of Trial Treatment (EOT) Visit .......................................................................... 36 
6.9 
End of Study (EOS) Visit........................................................................................... 37 
7 
ASSESSMENT OF SAFETY .............................................................................................. 41 
7.1 
Adverse Events .......................................................................................................... 41 
7.1.1 Definitions of Adverse Events .......................................................................... 41 
7.1.2 Recording of Adverse Events ........................................................................... 41 
7.1.3 Handling of Adverse Events ............................................................................. 41 
7.2 
Adverse Event/Serious Adverse Event Causality Assessment .................................. 41 
7.3 
Serious Adverse Events ............................................................................................. 41 
7.3.1 Definitions of Serious Adverse Events ............................................................. 41 
7.3.2 SAE Reporting by Investigators ....................................................................... 42 
7.3.3 Sponsor’s SAE Reporting Requirements ......................................................... 43 
7.4 
Recording of AE and SAE ......................................................................................... 43 
7.4.1 Diagnosis vs. Signs and Symptoms .................................................................. 43 
7.4.2 Persistent or Recurrent Adverse Events ........................................................... 44 
7.4.3 Abnormal Laboratory Values ........................................................................... 44 
7.4.4 Deaths 44 
7.4.5 Hospitalization, Prolonged Hospitalization, or Surgery ................................... 44 
7.4.6 Pre-existing Medical Conditions ...................................................................... 45 
7.4.7 Pregnancy, Abortion, Birth Defects/Congenital Anomalies ............................ 45 
7.4.8 New Cancers ..................................................................................................... 45 
7.4.9 Lack of Efficacy ............................................................................................... 45 
7.5 
Protocol-Defined Events of Special Interest .............................................................. 45 
7.5.1 Pregnancy, Abortion, Birth defects/Congenital anomalies .............................. 45 
7.5.2 Overdose ........................................................................................................... 46 
7.6 
Dose Modifications .................................................................................................... 46 
8 
ASSESSMENT OF EFFICACY ......................................................................................... 50 
8.1 
Specification of the Efficacy Parameters ................................................................... 50 
8.2 
Images included in the assessment. ............................................................................ 50 
8.3 
Measurable and non-measurable disease: .................................................................. 50 
8.3.1 Measurable Disease .......................................................................................... 50 
8.3.2 Non-Measurable Disease .................................................................................. 51 
8.4 
Baseline Lesion Selection and Documentation .......................................................... 51 
8.5 
Assessment of Response ............................................................................................ 52 
9 
STATISTICAL METHOD AND CONSIDERATIONS ..................................................... 53 
9.1 
General Considerations .............................................................................................. 53 
9.2 
Determination of Sample Size ................................................................................... 54 
9.3 
Study Population ........................................................................................................ 54 
9.4 
Statistical Analysis ..................................................................................................... 54 
9.4.1 Demographic and Baseline Characteristics ...................................................... 54 
9.4.2 Safety Analyses ................................................................................................ 54 
9.4.3 Efficacy analyses .............................................................................................. 54 
9.4.4 Exploratory Analyses ....................................................................................... 55 


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10 
ETHICAL, FINANCIAL, AND REGULATORY CONSIDERATIONS .......................... 55 
10.1 IRB/IEC Approval ..................................................................................................... 55 
10.2 Regulatory Approval .................................................................................................. 55 
10.3 Insurance and Indemnity ............................................................................................ 55 
10.4 Financial Disclosure and Obligations ........................................................................ 56 
10.5 Informed Consent ....................................................................................................... 56 
10.6 Confidentiality ........................................................................................................... 56 
10.6.1 Patient Confidentiality ................................................................................... 56 
10.6.2 Investigator’s Responsibilities ....................................................................... 57 
10.6.3 Investigator and Staff training and Information ............................................. 57 
11 
RECORD RETENTION AND DOCUMENTATION OF THE TRIAL ............................ 57 
11.1 Amendments to the Protocol ...................................................................................... 57 
11.2 Protocol Deviations .................................................................................................... 57 
11.3 Documentation Required to Initiate Trial .................................................................. 58 
12 
DATA HANDLING AND RECORD KEEPING ............................................................... 58 
12.1 Data Collection .......................................................................................................... 59 
12.2 Trial Monitoring, Auditing, and Inspecting ............................................................... 60 
12.3 Medical Monitoring ................................................................................................... 60 
12.4 Quality Assurance and Quality Control ..................................................................... 60 
13 
Disclosure and Publication Policy ....................................................................................... 61 
14 
REFERENCES .................................................................................................................... 61 
15 
APPENDICES ..................................................................................................................... 63 
Appendix A: ECOG Performance Status Scale ................................................................ 63 
Appendix B: Contraceptive Guidelines and Pregnancy ....................................................... 64 
Appendix C: Cytokines/Chemokines and Tumour Biopsy .................................................. 66 
 
List of Tables 
Table 1: PI3K δ, γ and SIK-3 inhibitors in clinical development for solid tumours ............................... 18 
Table 2 : Dosing Scheme ................................................................................................................. 24 
Table 3 : Laboratory Tests for Hematology, Chemistry and Urinalysis ................................................ 35 
Table 4 : ECG time points ................................................................................................................ 36 
Table 5 : Schedule of Events ............................................................................................................ 38 
Table 6 : Dose modifications for hematologic toxicity ........................................................................ 47 
Table 7 : Dose modifications for non-hematologic toxicity ................................................................. 48 
Table 8 : Guidance on Tenalisib Dose reduction ................................................................................ 50 
Table 9 : Response Assessment ........................................................................................................ 53 
  
List of Figures  
Figure 1: Study Design 
25 
Figure 2: Schema for screening 
34 
 
 
 
 


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1 
BACKGROUND INFORMATION  
1.1 
Background  
The phosphoinositide-3-kinases (PI3Ks) are a family of enzymes involved in various 
cellular functions including cell proliferation and survival, cell differentiation, intracellular 
trafficking and immunity. In hematological malignancies, inhibition of δ isoform is known 
to dampen the responsiveness of the tumour cells to supportive stimuli from the 
microenvironment. PI3K δ inhibitors act to a large extent by disrupting the interactions 
between the malignant B-cells, their protective stromal cells and immune cells, without 
directly killing the cancer cells. In solid tumours (e.g., breast and prostate cancer) p110 δ 
is shown to dampen the activity of PTEN tumour suppressor. Inactivation of p110 δ in 
these cells leads to PTEN activation, suppression of Akt phosphorylation, and inhibition of 
cell proliferation. Likewise, forced overexpression of p110 δ in cells with low p110 δ 
expression reduces PTEN activity, resulting in increased Akt phosphorylation.[1] This is 
exemplified by the frequent activating mutations in PIK3CA and the loss of PTEN 
functionality in common cancers such as breast, colon and ovary. In addition, the 
expression levels of p110δ protein seem to act as an intrinsic cancer-causing driver in 
various solid tumours including breast, prostate, colorectal, liver, merkel-cell carcinoma, 
glioblastoma and neuroblastoma.[1] Multiple p110δ selective inhibitors are being studied 
as potential single agent or in combination for treatment of solid tumours. (Table 1)  
 
The immunosuppressive microenvironment in tumour tissue is partly mediated by non-
tumoural stromal cells, most notably tumour associated macrophages (TAMs). These 
tumour-reprogramed macrophages shut down effector T and NK cell activities with soluble 
immunosuppressive factors and membrane-bound immune checkpoint molecules. Data has 
shown that PI3Kγ acts as a molecular switch turning on immunosuppression while shutting 
down immune-stimulatory activities. Inhibitors of PI3Kγ, can cause a shift/re-
programming leading to enhanced adaptive immunity, including increased recruitment and 
cytotoxicity of T cells.[2] This change in the immune environment significantly inhibit the 
growth and metastasis of tumours.[3] The PI3Kγ inhibitor (Eganelisib) is being studied as 
potential single agent or in combination for treatment of solid tumours. (Table 1) 
Activation of the PI3K/AKT pathway has been implicated in de novo and acquired 
treatment resistance to targeted therapies in multiple solid tumour.[4,5] In addition, PI3K 
also stabilizes and preserves double strand break (DSB) repair by interacting with the 
human recombinant complex under normal conditions[6] and is necessary for DNA repair 
during ionizing radiation.[7] PI3K inhibitors have shown to induce DNA damage in tumours 
that have defects in DNA damage-repair pathways, by disproportionately affecting the 
nonoxidative pentose phosphate pathway that delivers ribose-5-phosphate required for 
base ribosylation.[8] PI3K blockade also promotes Homologous Recombinant (HR) 
deficiency by downregulating BRCA1/2 and sensitizes BRCA-proficient tumours to poly-
ADP Ribose polymerase (PARP) inhibition. 


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Salt-inducible kinases (SIKs) are highly conserved serine/threonine protein kinases that 
belong to a family of AMP-activated protein kinases (AMPKs) and have a role in 
steroidogenesis, adipogenesis and regulation of tumour malignancy. SIKs are dysregulated 
in various cancers, including ovarian, breast, prostate, and lung cancers, indicating that 
SIKs may have role in tumour occurrence or progression.[9, 10] SIK-3 facilitates tumour cell 
resistance against cytotoxic T cell attack by shifting TNF signaling from apoptosis to 
survival. SIK3-specific inhibitors alone sensitize a wide array of human and murine cancer 
cell lines to TNF-induced apoptosis by engaging HDAC4/NFkB pathway.[11] 
SIK3 also governs G1/S process through upregulating the gene expression of cyclin D and 
cyclin E, downregulating the expression of p21 and p27, and increasing the Cyclin 
Dependent Kinase 2 (CDK2) activity. The absence of SIK3 leads to prolongation of mitosis 
in mice and human cells, thus increasing the sensitivity of cancer cells to a variety of anti-
mitotic drugs.[12] SIK3 also plays a positive role in mediating the high salt-induced 
inflammatory signal response that leads to cancer cell proliferation. SIK3 induces the 
upregulation of inflammatory arginine metabolism factors, such as iNOS and ass-1, and 
the downregulation of anti-inflammatory enzymes, such as arginase-1 and ornithine 
decarboxylase in breast cancer.[13]  Multiple SIK-3 inhibitors are being studied for 
treatment of solid tumours. (Table 1)  
 
Table 1: PI3K δ, γ and SIK-3 inhibitors in clinical development for solid tumours  
Drug name 
Selectivity 
Combination 
agent 
Indication 
Phase of 
the study 
PI3K δ inhibitor  
 
 
 
 
AZD8835 
PI3K α, δ 
Fulvestrant 
ER+, HER2-ve breast cancer 
Phase 1 
Parsaclisib 
PI3K δ 
INCMGA00012 
Advanced Solid Tumours 
Phase 1b 
BGB-10188 
PI3K δ 
Tislelizumab 
Advanced solid tumours. 
Phase 1/2 
Copanlisib   
PIK3 α, δ 
Eribulin 
TNBC 
Phase 1/2 
Trastuzumab 
HER2-positive Breast Cancer. 
Phase 1b/2 
PI3K γ inhibitor  
 
 
 
 
Eganelisib (IPI-549) 
PI3K γ  
Atezolizumab/ 
Nab Paclitaxel  
Triple-Negative Breast Cancer 
Phase 2 
SIK3 inhibitor 
 
 
 
 
GRN-300/ ARN-3261  SIK2/3 
Paclitaxel 
Ovarian Cancers 
Phase I 
OMX-0370/ IMT-07 
SIK3 
- 
Advanced Solid Tumours 
Preclinical 
ARN-3236 
SIK2 
- 
Advanced Solid Tumours 
Preclinical 
 
1.2 
Tenalisib (RP6530) 
Tenalisib is a highly specific and orally available dual PI3K δ/γ and SIK-3 inhibitor with 
nano-molar inhibitory potency and several fold selectivity over α and β PI3K isoforms. 
The specificity of tenalisib towards PI3K δ and γ is evidenced by >1000 and >100-fold 
selectivity over α and β isoforms in an enzyme-based assay. Chemically, tenalisib is an iso-
flavone substituted adenine.  
 
 
 


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1.3 
Pre-clinical Studies with RP6530 
Tenalisib has equimolar potency against both PI3K δ/γ isoforms in enzyme, cell, and 
blood-based assays. Additionally, the compound inhibited antigen-induced superoxide or 
cytokine release from primary human neutrophils or monocytes at nano-molar 
concentration indicating the potential in modulation of the tumour microenvironment. 
Studies using immortalized B and T lymphoma cell lines demonstrated the anti-
proliferative effect of tenalisib coupled with induction of apoptosis and a concomitant 
inhibition of the downstream biomarker, pAKT. Similarly, cytokine induced pAKT was 
inhibited in malignant primary CTCL cells isolated from patient donors.[14] 
In case of solid tumours, in MC38 syngeneic murine colon carcinoma model in 
immunocompetent C57BL/6 female mice, treatment with tenalisib showed tumour growth 
inhibition (TGI) of 29% as compared to control. The combination of tenalisib and anti-
PD1 reduced a mean tumour volume by 63% as compared to control.  
Combination of tenalisib and IN0385 (the major metabolite of tenalisib) potentiated the 
activity of taxol and doxorubicin in attenuating the growth of breast cancer cell lines. In 
another study, IN0385 demonstrated its activity as a single agent and in combination with 
a PARP inhibitor, talazoparib in ovarian cancer cell lines. Addition of IN0385 potentiated 
the activity of talazoparib. Similarly, IN0385 demonstrated its activity in combination with 
olaparib in breast cancer cell lines. IN0385 also potentiated the TNF-α mediated inhibition 
and apoptosis in breast cancer, AML and pancreatic cancer cell lines, and combination of 
TNF-α and IN0385 resulted in GI50 shift of IN0385 to left and significant inhibition of cell 
proliferation. Refer to the Investigator’s Brochure (IB) for detailed background 
information on tenalisib.[14] 
 
1.4 
Clinical Experience  
As of 20th April 2021, a total of 169 patients with relapsed/refractory hematological 
malignancies (viz. CLL, PTCL, CTCL and iNHL) have been exposed to tenalisib in either 
single agent or combination studies; 35 patients in RP6530-1301 study, 58 patients in 
RP6530-1401 study, 2 patients in RP6530+Pembrolizumab-1701 study, and 33 patients 
RP6530+Romidepsin-1805 study, 20 patients in RP6530-1802 study, 21 patients in 
RP6530-1901 study. A total of 16 patients have been rolled over to compassionate study 
(RP6530-1803); 4 from RP6530-1401 study, 5 from RP6530+Romidepsin-1805 study and 
7 from RP6530-1901 study. In addition, 18 healthy volunteers were exposed to tenalisib in 
food effect study (RP6530-1501). 
 
• 
Safety:  
169 patients have received tenalisib at doses ranging from 25-1200 mg BID. Tenalisib is 
generally well tolerated in patients with hematological malignancies (at doses ranging from 
25 mg BID to 1200 mg BID) and aggressive lymphomas such as TCL (at doses ranging 
from 200 mg BID to 800 mg BID). The most frequently reported related AEs (all grades) 
that occurred in more than 10% of patients included alanine aminotransferase (ALT) 
increased, aspartate aminotransferase (AST) increased (15.6% each) and diarrhea (11.9%). 
The most frequently reported related Grade ≥3 AEs were ALT increased, AST increased 
(7.4% each) and neutropenia (4.4%). Other Grade ≥3 laboratory abnormalities included 
gamma-glutamyl transferase (GGT) increased, International normalized ratio (INR) 


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increased, hyperglycemia and hypertriglyceridemia reported in one patient each. 
Hypophosphatemia and thrombocytopenia were reported in two patients.  
 
• 
Pharmacokinetics:  
In RP6530-1301 study, pharmacokinetics (PK) was evaluated in patients with 
hematological malignancies at doses ranging from 25-1200 mg BID and in TCL at doses 
ranging from 200 to 800 mg BID. Maximum systemic exposures assessed by AUC0-t as 
determined on Cycle 1 Day 1 (C1D1) were found at these doses. Tenalisib showed rapid 
absorption (between 0.5 and 2 h), with Cmax and AUC0-t increasing proportionately with 
dose on C1D1. There was no significant accumulation between C1D1 and C2D1. Trough 
concentrations did not show any specific trends from one day to the other even though 
concentrations increased generally with doses. T1/2 were similar for all dose levels. 
 
Clinically relevant concentrations of IN0385, a major metabolite of tenalisib, were 
observed in patients treated with tenalisib. Exposures (Cmax) for IN0385 ranged between 
1.2 to 2.2 times of tenalisib (the parent compound). Elimination kinetics of IN0385 were 
however similar to tenalisib with half-life ranging between 2 - 4.5 hours.   
 
• 
Efficacy:  
In Phase I study (RP6530-1301 study) in hematological malignancies, two patients (6.5 %) 
showed CR and 4 patients (12.9%) showed PR in 31 efficacy evaluable patients. The ORR 
was 19.4 % with a DCR of 61.3%. Duration of response was 5.68 (1.5-15.7) months. The 
time to onset of response was 3.49 months (1.4-11.9 months). PFS was 4.62 months (1.0-
17.5 months). 
 
In patients with TCL (RP6530-1401 study), a total of 16 out of 35 evaluable patients 
responded to tenalisib with ORR of 45.7% and a median DOR being 4.37 months. The best 
response of CR was noted in a total three (8.6%) patients while PR was noted in 13 (37.1%) 
patients. The ORR among CTCL and PTCL patients were similar and were 45.0% and 
46.7% respectively. The median DOR among PTCL patients was 4.9 months whereas it 
was 3.83 months in CTCL patients. 
 
In patients with indolent NHL (RP6530-1802 study), 20 patients received tenalisib in Part 
1. Only one FL patient showed a PR out of 19 evaluable patients in the study. In patients 
with CLL (RP6530-1901 study), seven patients showed PR with ORR of 33% in 21 
evaluable patients of Part I. Remaining 14 patients showed a stable disease. The median 
DOR was 5.23 months. 
 
 


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1.5 
Rationale  
1.5.1 Study Rationale 
Breast cancer is the most common cancer diagnosed in women and is the second leading 
cause of cancer-related deaths. It is categorized into different histopathological subtypes 
based on expression of estrogen receptor (ER), progesterone receptor (PR), and human 
epidermal growth factor receptor 2 (HER2). HR-positive, HER2-negative breast cancer is 
the most common subtype. Most patients with HR-positive, HER2-negative breast cancer 
are initially diagnosed and treated at an early stage with a combination of surgery with or 
without radiation and adjuvant endocrine therapy with or without adjuvant chemotherapy.  
 
Approved therapies for patients with HR-positive, HER2-negative advanced or metastatic 
breast cancer include hormonal-based (aromatase inhibitor [AI], fulvestrant) therapies in 
combination with CDK 4/6 inhibitors (abemaciclib, palbociclib, ribociclib), everolimus 
with exemestane, alpelisib with fulvestrant, hormonal monotherapy (AI, fulvestrant, 
tamoxifen), and chemotherapy (capecitabine, eribulin, ixabepilone, paclitaxel protein-
bound, gemcitabine, etc.).[15] Metastatic breast cancer is incurable and has a 5-year survival 
rate of approximately 25%. Treatment options for all patients remain an area of significant 
unmet need. 
 
The PI3K pathway is a central oncogenic pathway that regulates cell proliferation, cell 
metabolism, growth, survival, and apoptosis. Constitutive activation of PI3K down 
signaling is a critical step in mediating the transforming potential of oncogenes and tumour 
suppressors in many tumour types. Constitutive activation of the PI3K pathway has also 
been linked to resistance for a variety of therapeutic interventions, including chemotherapy, 
hormonal therapy, and anti-HER2 therapies. Similarly, activation of the PI3K pathway has 
been linked to de novo or acquired resistance to endocrine therapy, chemotherapy, and 
radiotherapy. Targeting PI3K pathway is therefore a potential therapeutic strategy for 
breast cancer.  
 
Furthermore, in some solid tumours p110 δ is shown to dampen the activity of PTEN 
tumour suppressor. Given that PTEN somatic mutations occur in a small percentage of 
human breast cancers and that p110 δ is highly expressed in this tumour type, PI3K δ 
inhibitors may provide an excellent opportunity in the intervention of breast cancer. PI3Kγ 
plays major role in immunosuppressive microenvironment. PI3Kγ inhibitors plays major 
role modulation tumour micro-environment leading to inhibition of tumour growth and 
metastasis.  
 
Overexpression of SIK is found in specific types of cancer such as ovarian and breast 
cancers. SIK3 is highly expressed in around 55% breast cancer patients. Elevated SIK3 
expressions in breast cancer cells are shown to contribute to tumourigenesis. Mechanistic 
studies have demonstrated that SIK3 played a crucial role in induction of G1/S‑phase 
release of cell cycle, along with enhanced expression of metastasis specific chemokine 
CXCR4 in breast cancer cells. The phosphorylation of HDAC4, a well‑documented 
downstream target of SIK3, is known to induce cell proliferation and malignancy.[16] Also, 
high expression of SIK3 stimulates mTOR-mediated aerobic glycolysis and cell 
proliferation of breast cancer cells.[17]   
 


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These evidences suggest the role of PI3K and SIK in oncogenesis and its maintenance and 
hence its inhibition can potentially lead to inhibition of growth of locally advanced or 
metastatic breast cancers. Several PI3K inhibitors, most of which are orally administered, 
either with broad activity against all PI3K isoforms or selectivity for specific isoforms, are 
in clinical development (Table 1). 
 
Tenalisib is a highly selective PI3K δ/γ and SIK3 inhibitor with a differentiated safety 
profile. In addition to PI3K class effects, anti-tumour activity of tenalisib is through three 
distinct and non-overlapping mechanisms; a) inhibition of δ isoform enhances an anti-
tumour cytotoxic T-cell response by reducing the immune-suppressive function of 
regulatory T cells (Tregs), b) inhibition of γ isoform decreases tumour growth by 
modulating tumour micro-environment, c) Inhibition of SIK3 potentiates the activity of 
TNF-α and thus increases apoptosis.  
 
Tenalisib has been evaluated in >150 patients with haematological malignancies and 
demonstrated encouraging activity in indications such as T-cell lymphoma (TCL) and 
Hodgkin’s Lymphoma (HL). The added influence of SIK-3, which is relevant to solid 
tumours, could potentially augment the activity of tenalisib in aggressive tumours.  
Tenalisib demonstrated pre-clinical activity as a single agent and in combination in 
multiple cell lines and syngeneic model representative of various solid tumours. In MC38 
syngeneic murine colon carcinoma model in immunocompetent C57BL/6 female mice, 
treatment with tenalisib reduced a mean tumour volume with TGI of 29% as compared to 
control. The combination of tenalisib and anti-PD1 reduced a mean tumour volume with 
TGI of 63% as compared to control, possibly indicating modulation of tumour micro-
environment through inhibition of γ isoform by tenalisib.[14]  
Combination of tenalisib and IN0385 potentiated the activity of taxol and doxorubicin in 
attenuating the growth of breast cancer cell lines. In another study, IN0385 demonstrated 
its activity as a single agent and also in combination with talazoparib in ovarian cancer cell 
lines. Addition of IN0385 at 5μM potentiated the activity of talazoparib. Similarly, IN0385 
demonstrated its activity in combination with olaparib in breast cancer cell lines. Addition 
of IN0385 potentiated the TNF-α mediated inhibition and apoptosis in breast cancer, AML 
and pancreatic cancer cell lines, and combination of TNF-α and IN0385 resulted in GI50 
shift of IN0385 to left and significant inhibition of cell proliferation. [14]    
 
Based on these pre-clinical evidences with tenalisib and clinical evidences from other PI3K 
inhibitors, it is proposed that tenalisib has the potential to treat the patients with locally 
advanced and metastatic breast cancer. 
 
1.5.2 Rationale for Dose Selection 
The safety and tolerability of tenalisib has been established up to doses of 1200 mg BID 
(total daily dose of 2400 mg) in patients with relapsed/refractory hematologic 
malignancies.[18] No dose limiting toxicity was seen at this dose level. The efficacy of 
tenalisib at 800 mg BID has been evaluated as a single agent as well as in combination in 
patients with TCL and showed impressive response in this patient population. [19,20]  
 


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In this study of breast cancer, the objective is to evaluate two doses of tenalisib and thus 
identify the optimal dose amongst the two which shows signal of clinical efficacy with an 
acceptable safety profile. This dose can be thus taken ahead for further development. Hence 
doses of 800 mg BID and 1200 mg BID are proposed in this Phase II study.  
 
1.6 
Benefit and Risks of participation in the study 
It is expected that proposed doses of tenalisib have the potential to improve response rates 
and benefit rates, and also increase the progression free survival. However, all the patients 
in clinical trials generally cannot expect to receive direct benefit from treatment during 
participation, as clinical trials are designed to provide information about the effectiveness 
and safety of an investigational medicine. Additional details regarding specific benefits and 
risks for subjects participating in this clinical trial can be found in the accompanying IB 
and Informed Consent documents. 
 
This protocol is written considering the impact of COVID-19 on trial participants, site 
staff and sponsor staff. The protocol includes the following adaptations to minimize risk 
while prioritizing the overall well-being and best interests of all involved in the trial. 
With these priorities in mind, the protocol design still permits assessment of safety and 
efficacy of tenalisib. 
• 
Minimize the number of study visits to align with the trial endpoints. 
• 
Minimize the number of trial specific activities. The trial is designed to align with 
standard of care protocols for locally advanced and metastatic breast cancer. For 
example, obtaining data from standard of care assessments conducted during routine 
care, for the collection and reporting of some safety outcomes (vital signs, laboratory 
results) and imaging outcomes.  
• 
Conduct visits by telemedicine or by telephone at EOS visit, where permitted, when a 
participant is unable to attend the site physically. This will permit the timely 
collection of efficacy endpoints (example: response to treatment or progression) and 
safety data (e.g., AE, SAE, lab assessment).  
• 
Use of remote electronic consent, where permitted.  
 
In addition to the above items included in the protocol, ongoing risk assessments and 
monitoring of the COVID-19 situation will be conducted by the sponsor with input from 
the local investigators at both a site and country level. These ongoing assessments include 
changes to any of the following:  
• 
Potential impact on trial participants  
• 
Potential impact on trial site staff, including local or central IRBs/ECs.  
• 
Potential impact on sponsor/CRO staff conducting site monitoring and central review 
of data.  
 
The outcome of these ongoing assessments could result in site-specific or country-
specific mitigation plans, which could include:  
• 
Suspension of enrollment in that site or country  
• 
Suspension of on-site visits by participants in that site or country, replacing the 
physical data capture with some remote measures (telephone or telemedicine, where 
permitted)  


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• 
Suspension of on-site visits being conducted by the study monitor, replacing the 
monitoring with remote review of data and telephone contacts with the site.  
• 
Other mitigation plans, as appropriate. 
 
 
2 
TRIAL OBJECTIVES 
2.1 
Primary Objective 
− To assess the anti-tumour activity of tenalisib in patients with locally advanced or 
metastatic breast cancer. 
2.2 
Secondary Objective 
− To evaluate the safety and tolerability of tenalisib.   
2.3 
Exploratory Objective  
− Changes in serum cytokines/chemokines and tumour tissue gene expression post 
treatment with tenalisib. 
 
3 
TRIAL DESIGN 
3.1 
Trial End Points 
3.1.1 Primary Endpoint  
− Percentage of patients without disease progression at the end of 6 months.  
 
3.1.2 Secondary Endpoints  
− Overall Response Rate (ORR), Clinical Benefit Rate (CBR) and Progression Free 
Survival (PFS). 
− Adverse event (AE), Grade 3/4 AEs, serious adverse event (SAE) evaluated and graded 
using NCI-CTCAE Version 5.0. 
3.1.3 Exploratory Endpoints 
− Change from baseline in cytokine/chemokine levels post treatment with tenalisib.  
− Change in gene expression profiles as measured by RNA sequencing from tumour 
biopsy samples post treatment with tenalisib.   
 
3.2 
Design of Trial 
This is a Phase II, randomized, open label study, designed to evaluate the preliminary 
efficacy and safety of tenalisib at two dose levels (800 mg BID and 1200 mg BID) in 40 
patients with locally advanced or metastatic breast cancer. Twenty patients each, will be 
enrolled in Group 1 (Tenalisib 800 mg BID) and Group 2 (Tenalisib 1200 mg BID). Both 
groups will be run in parallel.  
 Table 2 : Dosing Scheme 
 
 
 
 
 
Groups  
Number of Patients  
Dose of Tenalisib 
Group 1 
20 
Tenalisib 800 mg BID  
Group 2 
20 
Tenalisib 1200 mg BID 


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Figure 1: Study Design 
 
Note:  
* Disease will be re-assessed at C3D1 (± 7 days) and approximately 8 weeks thereafter (± 7 days), and/or at 
the EOT and/or as clinically indicated (if clinical progression is suspected). 
** Patients will undergo the end-of-treatment (EOT) assessments within 7 days after last dose of study drug 
or discontinuation.   
 
3.3 
Randomization  
This is a randomized, open label study. Eligible subjects will be randomized to one of the 
two groups (Group 1: Tenalisib 800 mg BID and Group 2: Tenalisib 1200 mg BID) in 1:1 
ratio based on the central randomization list generated by a validated software.  
 
3.4 
Investigational Medicinal Product 
3.4.1 Dosage Form and Strengths 
   A single strength of tenalisib tablet will be used in the study. 
 
Investigational Product(s) 
Dosage form, strength 
Tenalisib (RP6530) 
Tablets 400 mg  
Note: Please refer Investigator’s Brochure for additional information of Tenalisib  
 
3.4.2 Labeling, Packaging and Supply 
Tenalisib will be appropriately labeled and packaged as per local regulatory requirements 
and will be supplied to the sites through Rhizen Pharmaceuticals/designee. Tenalisib will 
be available as 30 tablets per bottle. Recommended storage condition is “Store at 20 to 
25°C, excursions permitted between 15°C and 30°C”. 
 


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3.4.3 Guidelines for administration of Tenalisib 
- Method of administration: Tenalisib will be administered orally twice daily in a 28-day 
cycle (Day 1-28). 
- Premedication: None. 
- Tenalisib tablets will be self-administered orally twice daily one hour before a major 
meal (e.g., breakfast and dinner). Patients should not consume food during this one-hour 
period.  
- Tenalisib tablets should be taken at approximately same time each day. Tablets should 
be swallowed; and should NOT be crushed or chewed.  
- If a dose of tenalisib is missed, it should be taken as soon as possible on same day with 
an interval of minimum 8 hours between two doses. If it is missed for the entire day, it 
should not be repeated. 
- If vomiting occurs, no attempt should be made to replace the vomited dose.  
- Study drug compliance should be reviewed with the patient at the beginning of each 
new treatment cycle. Missed doses should be documented. 
 
3.4.4 Accountability of Investigational Medicinal Products 
The PI/designee is responsible for the receipt of investigational medicinal product 
(tenalisib) and accountability of supplies at the site. During monitoring visit, the study 
monitor will ensure that all IMP related documentation is current and accurate. Study 
monitor will verify the drug accountability logs to ensure that the IMP has been dispensed 
as per the protocol and all the relevant information is documented. He will conduct an 
inventory of the remaining IMP at the site. All tenalisib inventories must be made available 
for verification by the monitor, sponsor representatives and regulatory agency 
inspectors/monitor upon request.  
 
Following study monitor’s verification and instruction, expired or unused investigational 
product can be returned to the sponsor or destroyed according to local institutional policy 
with sponsor pre-approval of a site-specific destruction policy. Certificate(s) of destruction 
or documentation of destruction must be filed at the site and in Trial Master File. Used, 
returned trial drug can be destroyed according to local institutional policy with sponsor 
pre-approval of a site-specific destruction policy. Certificate(s) of destruction or 
documentation of destruction must be filed at the site and in the Trial Master File. 
 
3.4.5 Precautions and Risks Associated with Investigational Product 
- Monitoring of liver enzymes and levels of TSH, T3, and T4 in patients receiving 
tenalisib is recommended based on target organ toxicity. Patients will be monitored for 
increased ALT/AST, skin rash, neutropenia as these are reported with tenalisib. In 
addition, events like enteritis (colitis), pneumonia/pneumonitis would also be looked for 
as they have been reported with other PI3K inhibitors. Tenalisib elicits no photo 
instability upon exposure to ultraviolet (UV) radiations. However, in absence of in-vitro 
data, possibility of photo-toxicity with tenalisib cannot be ruled out.  
- Tenalisib shows inhibition of CYP3A4 enzyme. Therefore, concomitant administration 
of tenalisib with predominant CYP3A4 substrates (e.g., calcium channel blockers, 


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warfarin, carbamazepine, macrolide antibiotics, lovastatin, simvastatin, terfenadine) 
may reduce clearance of these drugs increasing the risk of adverse events.  
- Similarly, as tenalisib is inhibited by CYP3A4/5 and CYP2C9, there is possibility of 
drug interaction with inhibitors or inducers of CYP3A4 and CYP2C9. If concomitant 
treatment with these drugs is clinically warranted, careful observation of the patient is 
advised. Strong inhibitor or inducers should be avoided as directed in Section 5.3 on 
prohibited medication. Please refer to the recent Investigator Brochure for additional 
safety information.[14] 
  
3.5 
The Expected Duration of Patient Participation and Follow-up 
The expected duration of patient participation in the study will be approximately 24 
months, unless the patient is discontinued from the study due to disease progression, drug 
toxicity or consent withdrawal.  
 
3.6 
Study Stopping Rules 
The study will be terminated if emerging safety findings confirm increased risk to the 
patients or a significantly altered risk-benefit assessment. Examples include but are not 
limited to the following: 
 
- New toxicological or pharmacological findings that significantly alter the risk benefit     
assessment or more SAEs of similar nature which in the opinion of the investigator, are 
the result of tenalisib, and hence place remaining patients at risk. 
- The sponsor may decide to discontinue the study if it becomes apparent that patient 
enrollment is unsatisfactory, and/or for administrative reasons. 
 
Regulatory authorities and respective IRB(s)/EC’s will be notified if the trial terminates 
early with a justification for the early termination. 
 
4 
SELECTION AND WITHDRAWAL OF PATIENTS  
4.1 
Inclusion Criteria 
Individuals should meet all the following criteria to be considered eligible to        
participate in the study:  
1. Provision of full informed consent prior to any study-specific procedures.  
2. Patients must be ≥18 years of age, at the time of signing informed consent. 
3. Female patients who have histologically and/or cytologically confirmed locally 
advanced or metastatic breast cancer that has progressed following at least one line 
of therapy.  
4. Patients with at least one measurable lesion per RECIST version 1.1 at baseline that 
can be accurately assessed by CT scan or MRI and is suitable for repeated assessment 
at follow up-visits.   
5. ECOG performance status 0 to 2.  
6. Life expectancy of at least 3 months. 
7. Adequate bone marrow, liver and renal functions as assessed within 7 (±2) days 
before the first dose of study drug with the following laboratory requirements: 
a. Hemoglobin ≥ 8.0 g/dL (should not be transfused or treated with erythropoietin 
to maintain or exceed this level) 
b. Absolute neutrophil count (ANC) ≥ 1.0 x 109/L without growth factor support 


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c. Platelet count ≥ 75 x 109/L  
d. Total bilirubin ≤ 1.5 times the ULN (or ≤ 3 x ULN, if the patient has Gilbert 
syndrome)  
e. ALT and AST ≤ 3 x ULN (≤ 5 x ULN for patients with liver metastasis or liver 
involvement)  
f. Creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault 
formula) for patients with creatinine levels above ULN. 
8. Female patient of childbearing potential should be willing to use a medically 
acceptable method of contraception as defined in Appendix B while participating in 
the study and for 30 days after the last dose of study drug AND must have a 
negative serum pregnancy test within 3 days prior to Cycle 1 Day 1 (C1D1).  
9. Ability to swallow and retain oral medication. 
10. Willingness and capability to comply with the study requirements. 
 
4.2 
Exclusion Criteria 
Individuals who meet any of the following criteria will be considered ineligible to 
participate in the study:  
1. Patients with HER-2 positive breast cancer  
2. Patient receiving anticancer therapy (e.g., chemotherapy, biologic therapy, hormonal 
therapy or any other investigational product) within 4 weeks or 5 half-lives of the 
drug prior to C1D1, whichever is shorter. Treatment interval will be 6 weeks for 
nitrosoureas or mitomycin C.  
3. Patient who has not recovered from acute toxicities (defined as NCI-CTCAE grade 
> 1) of previous therapy except treatment-related alopecia. (Note: Patient with any 
unresolved toxicities which in the opinion of PI are stable and controlled with 
medication can be enrolled in the study).  
4. Patients who have had disease progression within 8 weeks of platinum 
chemotherapy. (Note: Patients who have had a disease-free interval of more than 8 
weeks following platinum chemotherapy; and patients with previous neoadjuvant OR 
adjuvant platinum-based therapy can participate in the study).   
5. Prior exposure to investigational or marketed PI3K inhibitors (e.g., idelalisib, 
copanlisib, duvelisib, umbralisib, alpelisib, buparlisib) given for treatment of breast 
cancer. 
6. Major surgery within 4 weeks of starting study treatment OR any patient who has not 
recovered from the effects of major surgery.  
7. Patient with symptomatic uncontrolled brain metastasis. (Note: A scan to confirm the 
absence of brain metastases is not required. Patients whose brain metastatic disease 
has remained stable for ≥ 4 weeks (prior to the start of study treatment) following 
treatment of brain metastases are eligible. The patient can receive a stable dose of 
corticosteroids before and during the study if steroids were started at least 4 weeks 
prior to C1D1). 
8. HIV-positive patients who are on antiretroviral therapy OR active hepatitis C OR 
active hepatitis B virus infections.  
9. Ongoing immunosuppressive therapy including systemic corticosteroids except as 
allowed per concomitant medication. 
10. Known history of severe liver injury (e.g., alcoholic liver disease, primary biliary 
cirrhosis, ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver or 


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portal hypertension) as judged by investigator. (Note: Exception will be the patients 
with liver metastasis who can be enrolled in the study). 
11. History of severe cutaneous reactions (e.g., Drug Rash with Eosinophilia and 
Systemic Symptoms (DRESS), Stevens–Johnson syndrome (SJS) or toxic epidermal 
necrolysis (TEN) in the past. 
12. Active gastrointestinal tract disease with malabsorption syndrome or uncontrolled 
inflammatory gastrointestinal disease such as Crohn’s disease or ulcerative colitis. 
13. Myocardial infarction within 6 months before starting therapy, symptomatic 
congestive heart failure (New York Heart Association > Class II), unstable angina, 
or unstable cardiac arrhythmia requiring medication or clinically relevant findings in 
the ECG such as second-or third-degree AV block, significant prolongation of the 
QTcF interval unless agreed between the investigator and the medical monitor. 
14. Concurrent disease or condition that would interfere with study participation or 
safety, such as the following: 
o Active, clinically significant infection requiring parenteral antimicrobial agent. 
o Clinically significant bleeding diathesis or coagulopathy, including known 
platelet function disorder. 
o Mood disorders like OCD, severe depression, history of suicidal attempt, 
schizophrenia etc. as per the investigator’s discretion. 
15. Concurrent medications or substances with the potential to affect the activity or 
pharmacokinetics of tenalisib, as reviewed and confirmed by medical monitor.  
16. Pregnancy or lactation. 
17. Patient with other active malignancies at the time of screening except for adequately 
treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast, basal cell 
carcinoma of the skin or localized squamous cell carcinoma of the skin. (Note: 
Patients with prior malignancies which are treated and are in remission without 
requiring active treatment are allowed in the study). 
18. A serious uncontrolled medical disorder or active infection which would impair the 
ability of the patient to receive protocol therapy or whose control may be jeopardized 
by the complications of this therapy. 
 
Note: Post eligibility confirmation, biopsy will be performed in approximately 10-12 patients 
who have consented for biopsy, prior to the first dose on C1D1. Eligible patients who do not 
consent for biopsy will also be enrolled into the study. Blood will be collected in all patients 
for cytokine/chemokine analysis. 
 
4.3 
Discontinuation from Trial Treatment 
The patient will be discontinued from the study in case of any adverse event or procedure 
that poses increased risk to the patient or interferes with the study conduct; examples 
include but are not limited to the following:  
- NCI CTCAE version 5.0 Grade 3/4 non-hematological toxicities related to study drug 
that necessitate withdrawal in the opinion of investigator. 
- Development of an intercurrent illness, condition, or procedural complication, which 
could interfere with the patient’s continued participation.  
- Any other situation where in the opinion of the investigator, continued participation in 
the study would not be in the best interest of the patient.  
 
 


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In addition, patients will be discontinued from the study in the following circumstances.: 
- Consent withdrawal by patient (all patients are free to withdraw from participation in 
this study at any time, for any reasons, specified or unspecified, and without prejudice). 
- Non-compliance by study patients.  
- Pregnancy 
- Confirmed disease progression during therapy.   
- Discontinuation of the study by the Sponsor. 
 
Each patient discontinuation should be discussed with Medical Monitor and the reason for 
discontinuation should be documented. For all discontinued patients, the end of study 
safety assessment should be completed at the time of discontinuation. In case of 
discontinuation due to an AE, patient should be followed up for 30 calendar days from 
dosing or until resolution/stabilization of AE, whichever is earlier. Patients who have drug 
related CTCAE grade ≥ 3 laboratory abnormalities should be followed until the laboratory 
values have returned to CTCAE grade ≤ 2. 
 
Patients who are discontinued from the study at any stage will be considered for safety 
analysis. Patients who are discontinued from the study for reasons other than safety may 
be replaced as advised by the Medical Monitor, unless the Medical Monitor deems it 
unnecessary based on duration of the follow-up completed by the patient. 
 
 
5 
TREATMENT OF PATIENTS  
5.1 
Administration of Tenalisib 
Tenalisib will be administered orally twice daily in a 28-day cycle (Day 1-28) up to 2 years 
until progression of disease or toxicity warranting discontinuation of therapy.   
 
5.2 
Concomitant Medications 
In general, any concomitant medications should be avoided during the course of the study, 
unless it is required as a standard of care (necessary supportive care), prophylaxis or for 
the treatment of adverse event in the opinion of the treating investigator. The below 
recommendations should be followed, and concomitant medication should be clearly 
documented.  
- Antimicrobial and/or anti-viral prophylaxis should be used according to local standard 
practice; Pneumocystis jirovecii pneumonia (PJP) and herpes zoster prophylaxis is 
strongly recommended. Similarly, chronic carriers of HBV should receive prophylactic 
anti-viral therapy.  
- Hematopoietic growth factors (e.g., erythropoietin, GM-CSF and G-CSF) can be used 
for the management of acute toxicities such as febrile neutropenia when clinically 
indicated or at the discretion of the investigator.   
- Prophylactic anti-emetic treatment is discouraged at the start of study treatment; 
however, patients can receive appropriate anti-emetic treatment at the first onset of 


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nausea or vomiting and as required thereafter, in accordance with local standard 
practice.  
- Transfusions may be given, based on standard criteria and clinical judgment.  
- Corticosteroids are allowed for the symptomatic control of brain metastases provided 
the dose is stable before and during the study and they are started at least 4 weeks prior 
to the start of study treatment.  
- Bisphosphonates (e.g., zoledronic acid and pamidronate) and monoclonal antibody 
denosumab are allowed for bone metastases/bone pain.  
- Concurrent palliative radiotherapy for pain relief is allowed at the site of bone 
metastases that were present at baseline, provided the investigator does not feel that 
these are indicative of clinical disease progression during the study period; and 
radiotherapy is limited to an area other than the sole site of measurable or evaluable 
disease. Study treatment should be discontinued for a minimum of 3 days before a 
patient undergoes palliative radiation.  
- If concomitant treatment of drugs metabolized by CYP3A4/CYP2C9 enzymes are 
clinically warranted, careful observation of the patient is advised. 
- Low molecular weight heparin (LMWH) and Direct Oral Anticoagulant (DOA) such as 
dabigatran and edoxaban are acceptable for prophylaxis and/or treatment of venous 
thrombosis. Careful observation of the patient is advised while using apixaban and 
rivaroxaban.  
- Any Covid-19 vaccine (e.g., mRNA, viral vector and inactivated vaccine), and other 
inactivated vaccines are allowed and can be given as per the institutional guidance.  
- Any other treatment (except anti-cancer therapy as mentioned in the prohibited 
medication) which is required as a part of standard of care of the institution. However, 
this should be discussed with Medical Monitor and documented. 
 
5.3 
Prohibited Medications 
The following treatments are prohibited while on clinical trial:    
- Any other anti-cancer therapy (e.g., radiation therapy, hormonal, immunotherapy or 
biologic therapy). 
- Strong inhibitors or inducers of CYP3A4. Patients should stop using these medications 
at least 48 hrs or 5 half-lives (whichever is shorter) prior to C1D1. 
- Strong inhibitors or inducers of CYP2C9. Patients should stop using these medications 
at least 48 hrs or 5 half-lives (whichever is shorter) prior to C1D1. 
- Substrates of CYP3A4 enzyme with a narrow therapeutic range. Patients should stop 
using these medications at least 48 hrs or 5 half-lives (whichever is shorter) prior to 
C1D1. 
- Use of heparin and warfarin for prophylaxis and/or treatment of venous thrombosis is 
prohibited. These drugs should be stopped at least 48 hrs prior to C1D1. 
- Herbal or alternative medicines are not allowed throughout the trial. Patients should stop 
using these medications at least 48 hrs prior to C1D1.  
- Live attenuated vaccine (e.g., Flu vaccine, pneumovax, varicella) should not be 
administered whilst the patient is receiving study medication.  
- Concurrent medications or substances with the potential to affect the activity of tenalisib 
as reviewed and confirmed by medical monitor. 
- Any other investigational agent. 
 


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Decision on discontinuation of the patient who received concomitant/prohibited 
medication will be taken by the PI in consultation with Medical Monitor on a case-to-case 
basis, after reviewing ongoing clinical benefit and risk. The decision to allow a patient to 
continue will be documented and archived at the site and at Rhizen. 
 
5.4 
Procedures for Monitoring Patient Compliance. 
The following measures will be employed to ensure treatment compliance. 
- The study staff will instruct patients to bring any unused study drug to the site.  
- The study staff/designee will count and record the number of used and unused study 
drug tablets.  
- The study coordinator will confirm adherence to the dosing regimen with the patient. 
- He/she will record the number of tablets returned, the date returned and determine 
treatment compliance before dispensing new medication to the study patient.  
- Compliance below 80% will require counseling of the patient by study site personnel.  
 
6 
TRIAL ASSESSMENT AND PROCEDURE  
6.1 
Overview 
The Schedule of Event summarizes the trial procedures to be performed at each visit and 
is divided into following: 
1. 
Screening (Day -28 to Day 0) 
2. 
On treatment procedures (C1D1 to EOT) 
3. 
End of Treatment (within 7 days from the last dose) 
4. 
End of Study (Day +30 from the last dose) 
 
Individual trial procedures are described in detail below. It may be necessary to perform 
these procedures at unscheduled time points if deemed clinically necessary by the 
investigator. Multiple procedures may be scheduled at the same time point relative to 
tenalisib.  
 
6.2 
Informed Consent   
The investigator or qualified designee must obtain written consent from each potential 
patient or each patient’s Legally Acceptable Representative (LAR) prior to participating in 
a clinical trial. Consent must be documented on an IRB/EC approved consent form. A copy 
of the signed and dated consent form should be given to the patient before participation in 
the trial.  
 
The initial informed consent form, any subsequent revised written informed consent form 
and any written information provided to the patient must receive the IRB/EC’s 
approval/favorable opinion in advance before use. The patient or his/her legally acceptable 
representative should be informed in a timely manner if new information becomes 
available that may be relevant to the patient’s willingness to continue participation in the 
trial. The communication of this information will be provided and documented via a 
revised consent form or addendum to the original consent form that captures the patient’s 
dated signature or by the patient’s legally acceptable representative’s dated signature. 
Specifics about a trial and the trial population will be added to the consent form template. 


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The informed consent will adhere to IRB/EC requirements, applicable laws and regulations 
and Sponsor requirements. 
 
6.3 
Screening 
During screening period, written informed consent must be obtained prior to the initiation 
of trial treatment and before any protocol-specific procedures are performed. An additional 
consent for tumour biopsy will be requested. Screening vitals, laboratory tests, as described 
in the Schedule of Events, will be performed as per institutional practice and will be 
reviewed by the site PI/designee. The laboratory tests should be done ≤ 7 calendar days 
prior to the initiation of trial treatment. Re-screening can be done at the discretion of PI.  
 
Radiological assessment and other investigations to document presence of disease should 
be performed within 28 days prior to C1D1. Documentation of serology status (HIV, HBV 
and HCV) will be done based on historical information. To be considered negative for 
active infection, following algorithm will be used:  
• HBV: HBc antibody should be negative or if HBc antibody is positive, HBVDNA 
should be undetectable 
• HCV: HCV antibody should be negative or if HCV antibody is positive, HCVRNA 
should be undetectable 
• 
HIV: HIV antibody should be negative. (HIV 1/ 2 antibody should be negative unless 
positive result is considered false positive by PI). 
 
Note: Patients who show evidence of hepatitis B infection (HBsAg positive [regardless of 
antibody status] or HBsAg negative but anti-HBc positive), need to be evaluated for 
initiation of HBV antiviral prophylaxis and should be closely monitored for HBV 
reactivation.  
 
Covid-19 testing prior to enrollment may be done as per the institutional practice/local 
requirements. 
 
6.3.1 Assignment of screening and randomization numbers 
All consented subjects who undergo at least one post-consent procedure will be given a 
unique screening number that will be used to identify the subject for all procedures that 
occur during screening. Post confirmation of the eligibility, subject will be assigned a 
randomization number.  
 
 
 
 


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Figure 2: Schema for screening 
Screening period  
Dosing  
Day -28 to Day 0 
Day 1 
 
 
 
 
 
 
 
 
Patient 
consent  
 
• Disease assessment 
• Radiological assessment 
• Laboratory assessment 
• Other assessments as part 
of eligibility assessment  
• Eligibility 
confirmation  
• Collection of blood 
sample for 
cytokine/chemokines 
• Tumour biopsy in 
consented patients 
 
First Dose of the 
study drug 
 
 
Note: Post eligibility confirmation, the biopsy will be performed in approximately 10-12 patients who 
have consented for biopsy, prior to the first dose on C1D1. Eligible patients who do not consent for biopsy 
will also be enrolled into the study. Blood will be collected in all patients for cytokine/chemokine 
analysis.  
 
6.3.2 Medical history   
Basic demographic and baseline characteristics will be collected during screening. In 
addition to the evaluation of a patient’s medical history in terms of study eligibility, all 
relevant medical conditions will be documented on the appropriate eCRF. Events occurring 
after signing of informed consent but prior to initiation of tenalisib, unless serious and due 
to a protocol mandated procedure, should be recorded on the Medical History eCRF. 
 
The patient’s entire oncology history will be collected on the appropriate eCRF including 
date of diagnosis for cancer (and other malignancy, if applicable), prior surgeries / 
treatments received for cancer, dates of treatment administration, best response achieved, 
date of progression and its assessment, and BRCA mutation status (if known). 
 
6.3.3 Prior and Concomitant Medication Review 
Prior medication: The investigator/qualified designee will review prior medication use, 
including any protocol-specified washout requirement, and record prior medication taken 
by the patient within 28 days before starting the trial (i.e., C1D1). Treatment for the disease 
for which the patient has enrolled in the study will be recorded separately and not listed as 
a prior medication. 
 
Concomitant medication: The investigator or qualified designee will record medication, if 
any, taken by the patient during the trial.  
 
6.3.4 Physical Examination 
Full physical examination: The investigator/qualified designee will perform a complete 
physical exam during the screening period and as defined in Schedule of Events. Physical 
examination will include systemic examination (General Appearance, HEENT, neck, 


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cardiovascular, lungs, abdomen, lymph nodes, genitourinary (as applicable), extremities, 
neurological, skin, and musculoskeletal). Physical examination also includes measurement 
of accessible nodes and the size of the spleen and liver. Clinically significant abnormal 
findings should be recorded as medical history.  
 
Abbreviated (symptom directed) physical examination: For cycles that do not require a full 
physical exam per the Schedule of Events, the investigator or qualified designee will 
perform a directed physical exam as clinically indicated depending on assessment of 
tumour, prior to trial treatment administration. After the first dose of trial treatment new 
clinically significant abnormal findings should be recorded as AEs. 
 
6.3.5 Vital Signs  
Vital signs include temperature, pulse, respiratory rate, weight and blood pressure and 
should be recorded as per institutional practice. Historical data can be used for height. 
Vitals will be done prior to the administration of study treatments, at the time points 
specified in schedule of events.  
 
 
6.4 
Laboratory Investigations 
Laboratory tests for hematology, chemistry and urinalysis are specified in Table 3. 
 
Table 3 : Laboratory Tests for Hematology, Chemistry and Urinalysis 
 
Hematology  
Chemistry Panel I 
Chemistry Panel II 
Urinalysis 
Other  
Hematocrit  
Total bilirubin 
Total Cholesterol 
Blood  
Serum β-hCG 
Hemoglobin 
Alkaline phosphatase  
Triglyceride (TG) 
Glucose  
Urine pregnancy test 
Platelet count 
ALT  
LDL 
Protein  
PT and INR 
WBC (Total and 
differentials) 
AST  
HDL 
 
Specific 
gravity  
 
Serology (Hepatitis 
B, Hepatitis C, HIV)- 
Historical 
data 
is 
acceptable.  
 
Absolute 
neutrophil count 
LDH 
T3, T4, TSH 
Microscopic 
examb 
GGT 
 
 
- 
Blood glucose 
 
 
 
Albumin 
Total protein 
Urea or BUNa 
Creatinine 
Sodium 
Potassium  
Calcium 
Phosphorous 
Chloride  
a Blood Urea Nitrogen is preferred, if not available Urea may be tested. 
b Microscopic exam, if abnormal results are noted 
 
NOTE: Laboratory results obtained during Screening should be used to determine 
eligibility criteria.  In situations where laboratory results are out of reference range, the 


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investigator may opt to retest the patient and the subsequent within range screening result 
may be used to confirm eligibility. 
 
Blood drawn for these tests will be specified in informed consent form (ICF) as per the site 
ICF requirements. All safety laboratory investigations will be performed locally at the site.  
Screening labs will be done within 7 calendar days prior to the initiation of trial treatment. 
If these initial examinations are obtained within 72 hours of Cycle 1 Day 1, the labs need 
not be repeated on C1D1 again.  
 
  
6.5 
12-Lead Electrocardiograms 
A single 12-lead electrocardiogram (ECG) will be obtained at designated time points using 
local ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, 
and corrected QT (QTc) intervals.  ECG will be performed after the patient has at least a 
5-minute rest. Additional ECGs will be obtained if clinically indicated.  
  
 
Table 4 : ECG time points   
Days  
Time points  
Screening  
Within last 28 days  
 
C1D1  
Pre-dose 
At 
other 
time points 
Pre-dose C2D1, C3D1 and at EOT visit 
 
 
 
6.6 
Tumour Biopsy 
When patient presents with a biopsiable tumour/nodes/metastatic lesion, an on-study 
tumour biopsy will be performed (only in patients who agree to provide consent for the 
biopsy). The biopsy will be done after eligibility confirmation and prior to first dose on 
C1D1. A second biopsy sample will be taken at C3D1.  
Tumour tissue collected during the study will be fixed and processed to a FFPE block.  
Details on shipping the FFPE block to the central genomics lab will be detailed in the 
laboratory manual  
 
6.7 
Serum Cytokines/Chemokines 
Correlative serum for cytokines/chemokines (refer Appendix C) will be collected at 
screening and at the C3D1. Blood samples will be obtained in all patients at baseline and 
at C3D1. Processed serum samples will be stored at the specified temperature until 
analysis. The analyses of correlative markers are exploratory evaluation and will not be 
used to guide treatment decisions in the dose escalation and expanded cohort of the study. 
See laboratory manual for blood/serum processing instructions. 
 
6.8 
End of Trial Treatment (EOT) Visit 
All discontinued patients will undergo the end-of-treatment (EOT) assessments within 7 
days after the last dose of study drug or discontinuation from the study. Radiological 
assessment will not be performed if done earlier within 28 days. 
 


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6.9 
End of Study (EOS) Visit 
All patients must be followed up telephonically for adverse events for 30 calendar days 
after the last dose of study drug. In case of drug related SAE/AE or treatment 
discontinuation due to adverse event, the patients will be followed till the 
resolution/stabilization of the AE or 30 days after the last study dose whichever is the 
earlier. 
 


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Table 5 : Schedule of Events  
Cycle 
Screening 
 
 
 
C1 
 
 
 
C2 
C3 
Monthly 
visits  
(C4 onward 
up to 2 
year)19  
 
Efficacy 
Visits  
(C5, C7, 
C9… up to 
2 year)20 
EOT21 
EOS22 
Day 
D-28 to 0 
D1 
D15 
D1 
D15 
D1 
D1 
D1 
- 
- 
Window period 
- 
 
±1 
±1 
±3 
±3 
±3 
±7 
+7 
+30 
Study Days 
D-28 to 0 
1 
15 
29 
43 
57 
- 
- 
- 
- 
Informed Consent1 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Demographics2 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Medical history3 
X 
X 
- 
- 
- 
- 
- 
- 
- 
- 
Vitals4 
X 
X 
X 
X 
X 
X 
X 
- 
X 
- 
Height and weight5 
X 
X 
X 
X 
X 
X 
X 
- 
X 
- 
Physical examination6 
X 
X 
X 
X 
X 
X 
X 
- 
X 
- 
ECOG Performance Status 
X 
X 
- 
X 
- 
- 
X 
- 
X 
- 
Complete blood count7 
X 
X 
X 
X 
X 
X 
X 
- 
X 
- 
Chemistry panel I8 
X 
X 
X 
X 
X 
X 
X 
- 
X 
- 
Chemistry panel II9 
X 
X 
- 
X 
- 
X 
X 
- 
X 
- 
HIV, HBV, HCV status 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
PT and INR10 
X 
X 
- 
X 
- 
X 
- 
- 
X 
- 
Cytokines/chemokines analysis11 
X 
- 
- 
- 
- 
X 
- 
- 
- 
- 
Urinalysis (routine) 
X 
X 
X 
X 
X 
X 
X 
- 
X 
- 
Pregnancy test12 
X 
X 
- 
- 
- 
- 
- 
- 
- 
- 
12-lead ECGs13   
X 
X 
- 
X 
- 
X 
- 
- 
X 
- 
Tumour biopsy 14 
X 
- 
- 
- 
- 
X 
- 
- 
- 
- 
Radiological assessment (CT and/or 
MRI) 15 
X 
- 
- 
- 
- 
X 
- 
X 
X 
- 
Bone scan16 
X 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Drug Dispensing17 
- 
X 
- 
X 
- 
X 
X 
- 
- 
- 


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Tenalisib administration18 
- 
X 
X 
X 
X 
X 
X 
- 
- 
- 
Drug compliance 
- 
X 
X 
X 
X 
X 
X 
- 
X 
- 
AE evaluation 
X 
X 
X 
X 
X 
X 
X 
- 
X 
X 
SAE evaluation 
X 
X 
X 
X 
X 
X 
X 
- 
X 
X 
Concomitant medication 
X 
X 
X 
X 
X 
X 
X 
- 
X 
X 
 
Foot notes: 
1. Patient should be re-consented, if informed consent is obtained > 30 days prior to the initiation of trial treatment. The first day of tenalisib administration 
will be considered as C1D1.   
2. Demographic profile will include age, sex and race.  
3. Detailed history will be taken at screening that includes history of cancer, past history, no of prior therapies and prior medication (in last 4weeks); and 
other medical history. Patient’s medical record must include prior treatments received, dates of administration, response to prior therapies and date of 
progression. 
4. Vitals will include pulse (sitting/supine); blood pressure (sitting/supine); respiratory rate and oral temperature. Vitals will be done at pre-dose at all 
visits.  
5. Weight will be measured at all visits. Height to be measured at screening only.  
6. Physical examination will include systemic examination (General Appearance, HEENT, neck, cardiovascular, lungs, abdomen, extremities, 
neurological, skin, and musculoskeletal). Complete physical examination will be done at screening visit. At subsequent visits, abbreviated examination 
will be done depending on the assessment of tumour. 
7. This will include Hb, complete blood count, total leucocyte and differential count and platelet count. Additional investigations will be performed if 
clinically indicated. Hematology must be done ≤ 7 days prior to initiation of treatment. However, if these initial examinations are obtained within 72 
hours of C1D1; they do not have to be repeated.      
8. Chemistry Panel I include blood glucose, albumin, total protein, total bilirubin, ALP, AST, ALT, GGT, LDH, urea or blood urea nitrogen, creatinine, 
sodium, potassium, chloride, calcium, phosphorus.  These tests must be done ≤ 7 days prior to initiation of treatment. However, if these initial 
examinations are obtained within 72 hours of C1D1; they do not have to be repeated. These tests will be performed at supplementary visits if clinically 
indicated.       
9. Chemistry Panel II includes total cholesterol, TG, LDL, HDL, T3, T4 and TSH. These tests must be done ≤ 7 days prior to initiation of treatment. 
However, if these initial examinations are obtained within 72 hours of C1D1; they do not have to be repeated. These tests will be performed at 
supplementary visits if clinically indicated.       
10. The tests must be done ≤ 7 days prior to initiation of treatment. However, if initial examination is obtained within 72 hours of C1D1; this does not have 
to be repeated. This test will be performed at supplementary visits if clinically indicated. 
11. Blood will be collected in all patients for serum cytokine/chemokine estimation at screening (baseline) and at C3D1.  
12. This is required for women of child-bearing potential. A serum pregnancy test will be performed at screening and 72 hours prior to dosing. Urine 
pregnancy test will be performed at other visits as indicated.  
13. ECGs will be performed at screening and C1D1 pre-dose to establish baseline cardiac activity. Additional ECGs will be obtained if clinically indicated. 
All ECGs will be performed on local equipment.  
14. A tumour biopsy will be performed in 10-12 patients who have consented for the biopsy. The biopsy will be done after eligibility confirmation prior to 
the first dose on C1D1. A second tumour biopsy sample will be taken at C3D1.  
15. CT and/ or MRI will be performed at the time of screening within 28 days of screening. Disease will be re-assessed at C3D1 (± 7 days) and approximately 
8 weeks thereafter (± 7 days), and/or at the EOT (not required if done within last 28 days) and/or as clinically indicated (if clinical progression is 


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suspected). If a CR or PR is noted, confirmatory scans should be performed at least 4 weeks after the initial response was first documented. Tumour 
imaging should remain consistent throughout the study and should include those thought by investigator to best capture status of disease. (Baseline scan, 
if already available as SOC within 28-days of screening is accepted as part of study protocol). Any other sites at which new disease is suspected should 
also be appropriately imaged.  
16. Bone scan will be done at the baseline when progression in bone is suspected. Bone scans need to be repeated only when complete response is reported 
in target disease or when progression in bone is suspected.  
17. Tenalisib will be dispensed in a HDPE container having 30 tablets of tenalisib.  
18. Tenalisib will be administered orally twice a day in 28-days of cycle. Tenalisib will be continued in patients experiencing clinical benefit for 24 months 
unless progression of disease or toxicity is observed warranting discontinuation of therapy. 
19. All visits will be done monthly from Cycle 3 onwards for 24 months (e.g. C4, C5, C6…. C26).  
20. All visits for efficacy assessments will be done at 8-weekly intervals (± 7 days) for 24 months (e.g.C5, C7…. C26).  
21. All patients will undergo the end-of-treatment (EOT) assessments within 7 days after last dose of study drug or discontinuation.   
22. Patients must be followed telephonically for adverse events for 30 calendar days after the last dose of study drug. 
 
 
 
 
 
 
 
 


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7 
ASSESSMENT OF SAFETY 
7.1 
Adverse Events 
7.1.1 Definitions of Adverse Events 
 
Any untoward medical occurrence in a patient or clinical investigation subject administered a 
pharmaceutical product and which does not necessarily have a causal relationship with this 
treatment. An adverse event (AE) can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of an investigational product, whether or not related to the investigational product.   
 
7.1.2 Recording of Adverse Events 
All adverse events of any patient during the course of the trial will be reported in the electronic 
Case Record Form (eCRF), and the investigator will give his or her opinion as to the relationship 
of the adverse event to trial drug treatment (i.e., whether the event is related or unrelated to trial 
drug administration). If the adverse event is serious, it should be reported immediately to Sponsor. 
Other untoward events occurring in the framework of a clinical trial are also to be recorded as 
AEs (i.e., AEs that occur prior to assignment of trial treatment that are related to a protocol-
mandated intervention, including invasive procedures such as biopsies, medication washout, or 
no treatment run-in). All AEs regardless of seriousness or relationship to tenalisib, spanning from 
the informed consent drug until 30 calendar days after the last dose of study drug are to be 
recorded in the electronic Case Record Form (eCRF).  
 
7.1.3 Handling of Adverse Events 
All adverse events resulting in discontinuation from the trial should be followed until resolution 
or stabilization. Patients must be followed for AEs for 30 calendar days after the last dose of study 
treatment. All new AEs occurring during this period must be reported and followed until 
resolution unless, in the opinion of the investigator, the adverse event or laboratory 
abnormality/ies are not likely to improve because of the underlying disease. In this case, the 
investigators must record his or her reasoning for this decision in the patient’s medical record and 
as a comment on the eCRF. After 30 days of completion of protocol-specific treatment or 
discontinuation, only AEs, SAEs, or deaths assessed by the investigator as treatment related are 
to be reported. 
 
7.2 
Adverse Event/Serious Adverse Event Causality Assessment  
Causality is assessing the relationship of the trial treatment to the adverse event. For this study, 
the causality assessment will be categorized as related and not related.  
• 
Related: All toxicities should be considered related to tenalisib unless there is a clear 
alternative explanation.   
• 
Not related:  If there is no temporal association, or another etiology has been identified as 
the cause, or the trial treatment cannot be implicated based upon the current information. 
 
7.3 
Serious Adverse Events 
7.3.1 Definitions of Serious Adverse Events 
The definitions of serious adverse events (SAEs) are given below. The principal investigator is 
responsible for ensuring that all staff involved in the trial is familiar with the content of this 
section. 
 


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An SAE or reaction is defined as any untoward medical occurrence that: results in death, is 
immediately life-threatening, requires at least a 24-hour in-patient hospitalization or prolongation 
of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital 
anomaly/birth defect or any important medical event.  
 
Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
appropriate in other situations, such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization, but may jeopardize the patient or may require 
intervention to prevent one of the other outcomes listed in the previous definition.  These should 
also usually be considered serious. Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do 
not result in hospitalization; or development of drug dependency or drug abuse. Progression of 
malignancy (including fatal outcomes), if documented by use of appropriate method (for 
example, as per RECIST version 1.1 criteria), should not be reported as a serious adverse event.  
 
Treatment within or admission to the following facilities is not considered to meet the criteria of 
“in-patient hospitalization” (although if any other SAE criteria are met, the event must still be 
treated as an SAE and immediately reported): 
• Emergency Department or Emergency Room 
• Outpatient or same-day surgery units 
• Observation or short stay in unit  
• Rehabilitation facility 
• Hospice or skilled nursing facility 
• Nursing homes, Custodial care or Respite care facility 
 
Hospitalization during the trial for a pre-planned surgical or medical procedure (one which is 
planned prior to entry in the trial or planned in advance and not related to the study procedure/ 
drug), does not require reporting as a serious adverse event to the Sponsor. 
 
7.3.2 SAE Reporting by Investigators 
It is important to distinguish between “serious” and “severe” adverse events, as the terms are not 
synonymous.  Severity is a measure of intensity; however, an AE of severe intensity need not 
necessarily be considered serious.  For example, nausea which persists for several hours may be 
considered severe nausea but may not be considered an SAE.  On the other hand, a stroke which 
results in only a limited degree of disability may be considered only a mild stroke but would be 
considered an SAE. Severity and seriousness should be independently assessed when recording 
AEs on the eCRF and SAEs on the SAE Report Form. 
 
Adverse events classified by the treating investigator as serious require expeditious handling and 
reporting to sponsor in order to comply with regulatory requirements.  Serious adverse events 
may occur at any time from the signing of the informed consent form through the 30-day follow-
up period after the last trial treatment. Sponsor/sponsor representative must be notified of all 
SAEs, regardless of causality, within 1 day of the first knowledge of the event by the investigator.   
 
To report an SAE, the SAE Report Form should be completed with the necessary information.  
All SAEs occurring from the signing of consent until 30 calendar days of last trial treatment must 


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be reported to the Sponsor as SAEs on the SAE Report and followed until resolution (with 
autopsy report if applicable). 
 
Deaths and other SAEs occurring > 30 calendar days after last trial treatment that are deemed 
related to tenalisib must be reported as SAEs on the SAE Report within 1 day of first knowledge 
of the event by the treating physician or research personnel (with an autopsy report if available). 
Deaths occurring > 30 calendar days after last trial treatment and not attributed to trial treatment 
(e.g., disease progression) need not be reported as SAEs, but simply captured on the appropriate 
eCRF. 
 
The SAE Report Form should be sent to the sponsor/sponsor representative via fax or e-mail 
within 24 hours of becoming aware of the event. The detailed SAE reporting process will be 
reviewed with sites during the site initiation visit as well as provided on the SAE report itself. 
Transmission of the SAE report should be confirmed by the site personnel submitting the report. 
Follow-up information for SAEs and information on non-serious AEs that become serious should 
also be reported to Sponsor as soon as it is available; these reports should be submitted using the 
SAE Report Form.   
 
Investigators must report SAEs and follow-up information to their responsible IRB/IEC 
according to the policies of the responsible IRB/IEC. 
 
7.3.3 Sponsor’s SAE Reporting Requirements 
Sponsor/Sponsor representative is responsible for reporting relevant SAEs to the competent 
authority, other applicable regulatory authorities, and participating investigators, in accordance 
with ICH guidelines, and/or local regulatory requirements. 
 
Sponsor/sponsor representative is responsible for reporting unexpected fatal or life-threatening 
events associated with the use of the trial drugs to the regulatory agencies and competent 
authorities via telephone or fax within 7 calendar days after being notified of the event.   
 
The Sponsor will report all related, unexpected SAEs, including non-death/non-life-threatening 
related unexpected SAEs associated with the use of the trial medications to the regulatory 
authority by a written safety report within 15 calendar days of notification. Reporting to the 
IRB/IEC will be done according to institutional policy. 
 
7.4 
Recording of AE and SAE 
Investigators should use correct medical terminology/concepts when recording AEs or SAEs on 
the SAE Report Forms and AE eCRF. Avoid colloquialisms and abbreviations. All AEs, 
including those that meet SAE reporting criteria, should be recorded on the AE eCRF; AEs that 
meet the definition of an SAE should additionally be reported following the procedures noted in 
above sections.  
 
7.4.1 Diagnosis vs. Signs and Symptoms 
All AEs should be recorded individually in the patient’s own words (verbatim) unless, in the 
opinion of the Coordinating Investigator or designated physician, the AEs constitute components 
of a recognized condition, disease, or syndrome.  In the latter case, the condition, disease, or 


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syndrome should be named rather than each individual sign or symptom.  If a constellation of 
signs and/or symptoms cannot be medically characterized as a single diagnosis or syndrome at 
the time of reporting, each individual event should be recorded as an AE or SAE as appropriate 
on the relevant form(s) (SAE Report Form and/or AE eCRF). If a diagnosis is subsequently 
established, it should be reported as follow-up information. If a diagnosis is determined 
subsequent to the reporting of the constellation of symptoms, the signs/symptoms should be 
updated to reflect the diagnosis. 
 
7.4.2 Persistent or Recurrent Adverse Events 
A persistent AE is one that extends continuously, without resolution, between patient evaluation 
time points. Such events should only be recorded once on the SAE Report Form. If a persistent 
AE becomes more severe or lessens in severity, AE should be recorded separately with new onset 
date in eCRF.    
 
A recurrent AE is one that occurs and resolves between patient evaluation time points, and 
subsequently recurs. All recurrent events should be recorded separately on an SAE Report Form 
and eCRF and should be reconciled later as a one event. Example of recurrent AEs include, but 
not limited to recurrent fall, recurrent transaminitis, recurrent elevated GGT.  
 
7.4.3 Abnormal Laboratory Values 
Any grade 3 or 4 laboratory abnormalities and clinically significant grade 1 or 2 laboratory 
value(s) should be recorded as an AE. Isolated laboratory abnormality without clinical 
significance should not be captured as AE if confirmed by the investigator. If an abnormal 
laboratory value or vital sign is associated with clinical signs and/or symptoms, the sign or 
symptom should be reported as an AE, and the associated laboratory value or vital sign should be 
considered additional information that must be collected on the relevant eCRF. If the laboratory 
abnormality is a sign of a disease or syndrome, only the diagnosis needs to be recorded on the 
SAE Report Form or AE eCRF. 
 
7.4.4 Deaths 
Deaths that occur during the protocol-specified AE reporting period that are attributed by the 
investigator solely to progression of disease will be recorded on the “Trial Discontinuation” eCRF 
and should not be reported as a SAE. All other on- trial deaths, regardless of attribution, will be 
recorded on an SAE Report and expeditiously reported to the Sponsor. 
 
When recording a serious adverse event with an outcome of death, the event or condition that 
caused or contributed to the fatal outcome should be recorded as the single medical concept on 
the SAE report and Adverse Event page of the eCRF. If the cause of death is unknown and cannot 
be ascertained at the time of reporting, record “Death NOS” on the eCRF Adverse Event page.  
 
7.4.5 Hospitalization, Prolonged Hospitalization, or Surgery 
Any AE that results in hospitalization of > 24 hours or prolonged hospitalization should be 
documented and reported as an SAE unless specifically instructed otherwise in this protocol. 
There are some hospitalization scenarios that do not require reporting as an SAE when there is 
no occurrence of an AE. (See section 7.3)  
 


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7.4.6 Pre-existing Medical Conditions 
A pre-existing medical condition is one that is present at the start of the trial.  Such conditions 
should be recorded on the General Medical History eCRF. A pre-existing medical condition 
should be recorded as an AE or SAE only if the frequency, severity, or character of the condition 
worsens during the trial. When recording such events on an SAE Report Form and/or AE eCRF, 
it is important to convey the concept that the pre-existing condition has changed by including 
applicable description. 
 
7.4.7 Pregnancy, Abortion, Birth Defects/Congenital Anomalies 
Pregnancy, abortion, birth defects, and congenital anomalies are events of special interest.  Please 
refer to pregnancy Section 7.5.1 for specific instructions. 
 
7.4.8 New Cancers 
The development of a new primary cancer should be regarded as an AE and will generally meet 
at least one of the serious criteria. New primary cancers are those that are not the primary reason 
for the administration of the study treatment and have developed after the inclusion of the patient 
into the study. They do not include new lesions of the original cancer. Symptoms of metastasis 
or the new lesions itself should not be reported as an AE/SAE, as they are considered to be disease 
progression. 
 
7.4.9 Lack of Efficacy 
When there is deterioration in the condition for which the study treatment is being used, there 
may be uncertainty as to whether this is lack of efficacy or an AE. In such cases, unless the 
sponsor or reporting physician considers the study treatment contributed to the deterioration of 
the condition, the deterioration should be considered lack of efficacy and not an AE. 
 
7.5 
Protocol-Defined Events of Special Interest 
The following are events of special interest and will need to be reported expeditiously. 
 
7.5.1 Pregnancy, Abortion, Birth defects/Congenital anomalies 
Female patients who are not of child-bearing potential (see Appendix B) and female patients of 
child-bearing potential who have a negative pregnancy test within 72 hours prior to C1D1 are 
eligible for the study. Female patients of child-bearing potential (see Appendix B)) must consent 
to use a medically acceptable method of contraception throughout the study period and for 30 
days after the last dose of tenalisib.  
 
During the course of the trial, all female patients of childbearing potential must contact the 
treating investigator immediately if they suspect that they may be pregnant (a missed or late 
menstrual period should be reported to the treating investigator).   
 
If an investigator suspects that a patient may be pregnant prior to administration of trial drug(s), 
the trial drug(s) must be withheld until the result of the pregnancy test is confirmed. If a pregnancy 
is confirmed, the patient must not receive any trial drug(s) and must be discontinued from the 
trial. The outcome of the pregnancy will be monitored as outlined in Appendix B. 
 


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If an investigator suspects that a patient may be pregnant after the patient has been receiving trial 
drug(s), the trial drug(s) must immediately be withheld until the result of the pregnancy test is 
confirmed. If a pregnancy is confirmed, the trial drug(s) must be immediately and permanently 
stopped, the patient must be discontinued from the trial, and the investigator must notify the 
Medical Monitor and Sponsor Representative as soon as possible. If a patient becomes pregnant 
while enrolled in the trial, a Pregnancy Form should be completed and faxed to the Sponsor. The 
outcome of the pregnancy will be monitored as outlined in Appendix B. 
    
Congenital anomalies/birth defects always meet SAE criteria, and should therefore be 
expeditiously reported as an SAE, using the previously described process for SAE reporting. A 
Pregnancy Form should also have been previously completed and will need to be updated to 
reflect the outcome of the pregnancy. 
 
7.5.2 Overdose 
An overdose is defined as accidental or intentional administration of any dose of product that is 
considered both excessive and medically important. For purposes of this trial, an overdose will 
be defined as any dose exceeding the proposed dose of tenalisib (i.e 1200 mg BID).   
 
Symptomatic and non-symptomatic overdose must be reported in the eCRF.  Any accidental or 
intentional overdose with the trial treatment that is symptomatic, but not fulfilling a seriousness 
criterion, is to be reported to the Sponsor immediately as an AE. All symptomatic overdose, 
fulfilling a seriousness criterion, is to be reported as an SAE as per the SAE reporting procedure. 
For patients who experience overdose, treatment should consist of supportive therapy. A decision 
to interrupt treatment or dose reduction to be taken depending on the symptoms.  
 
7.6 
Dose Modifications 
In case of hematologic and non-hematologic toxicities, the dose modifications provided below 
(Table 6 and Table 7) should be used as a guidance and should be determined as per PI’s clinical 
judgement. The dose modifications are intended to be applied when the investigator determines 
the events related to tenalisib. If events (cytopenia) are deemed related to the underlying disease 
rather than tenalisib, dose reduction will be done as per the investigator’s discretion. 
In case of drug withhold, tenalisib treatment can be resumed if:  
• Patient recovers from grade 3-4 toxicity as defined in dose modification guidance below.   
• No clinical or radiographic evidence of disease progression.  
• Investigator believes the risk of progression outweighs the risk of further treatment. 
 
If treatment is delayed >2 weeks, treatment continuation should be discussed with Medical 
monitor. The treatment should be permanently discontinued if withhold of study drug due to drug 
related toxicity is for > 28-days unless approved by medical monitor.  
 
At the discretion of the investigator, a dose re-escalation may be permitted for patients who earlier 
has dose reduction. The decision should be taken after evaluating the emerging safety data and 
benefit and risk of re-escalation. Drug holidays are discouraged. Any patient in whom similar 
toxicity recurs at the reduced dose, it should be discussed with medical monitor to determine 
appropriate strategy on treatment continuation.  
 
 


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Table 6 : Dose modifications for hematologic toxicity 
 
CTCAE Grade  
Action to be Taken 
Hematologic toxicity  
Grade 3 Neutropenia 
(1.0 X 109/L<ANC ≥ 0.5 
X 109 /L)  
• Maintain dose level. 
• Monitor ANC at least weekly.  
Grade 4 Neutropenia 
(0.5 x 109 /L<ANC)  
• First incidence: Hold dose until resolved to ≤ Grade 2 or 
baseline. Monitor ANC at least weekly. Resume treatment 
at the same dose level. 
• Subsequent occurrence: Hold dose until resolved to ≤ 
Grade 2 or baseline, consider growth factor support. 
Resume treatment at one dose lower* if warranted. 
• Discontinue if further dose modification required at lowest 
dose. 
Grade 3 Febrile 
neutropenia  
ANC <1.0 X 109/L with a 
single temperature of > 
38.30C (1010F) or a 
sustained temperature of ≥ 
380C (100.40F) for more 
than one hour. 
• Withhold dose until resolved to ≤ Grade 2 or baseline, 
consider growth factor support, then reduce by 1 dose 
level*, if warranted.  
• If the ANC is <1 X 109/L (1000/µL) before therapy, the 
dose shall not be modified as long as ANC >0.5 X 109/L. 
Grade 3 
Thrombocytopenia  
(50.0 X 109 /L< PLT ≥ 
25.0 X 109 /L) with Grade 
1 bleeding 
• Maintain dose level. 
• Monitor platelet count at least weekly.  
Grade 4 
thrombocytopenia 
(20.0 X 109/L< PLT)  
OR Grade 3 
thrombocytopenia with 
Grade 2 bleeding 
• 1st occurrence: Hold dose until to ≤ Grade 2 or baseline or 
resolution of bleeding. Consider platelet transfusion as 
necessary. Resume treatment at the same dose level. 
• Subsequent Occurrences: Hold dose until to ≤ Grade 2 or 
baseline or resolution of bleeding. Consider platelet 
transfusion as necessary. Resume treatment at one dose 
lower* if warranted.  
• Discontinue if further dose modification required at lowest 
dose*. 
Note: The drug interruption and dose modification should be discussed with medical monitor. 
*See ‘Guidelines for dose reduction’ below.  
 
 
 


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Table 7 : Dose modifications for non-hematologic toxicity 
Non-Hematologic Toxicity 
Infection 
Grade 3 or higher sepsis or pneumonia 
• Withhold tenalisib until infection has resolved. 
• Restart at the same or at the reduced dose level*, if warranted.  
Skin rash (Cutaneous 
reactions) 
Grade 1-2 
• Maintain tenalisib dose. Initiate supportive care with emollients, 
antihistamines (for pruritus), or topical steroids 
• Monitor closely until resolved. 
Grade 3 
• Withhold tenalisib dose. Initiate supportive care with emollients, 
antihistamines (for pruritus), or topical steroids 
• Monitor at least weekly until resolved. 
• Restart tenalisib at the reduced dose level*.  
• If severe cutaneous reaction does not improve, worsens, or 
recurs, discontinue tenalisib. 
Life threatening or SJS, TEN, DRESS (any grade) 
• Discontinue tenalisib permanently. 
Pneumonitis without 
suspected infectious 
cause 
Moderate (Grade 2) symptomatic pneumonitis 
• Withhold tenalisib dose. Initiate systemic steroid therapy. If 
pneumonitis recovers to Grade 0 or 1, tenalisib may be resumed 
at reduced dose*.  
• If non-infectious pneumonitis recurs or patient does not respond 
to steroid therapy, discontinue tenalisib. 
Severe (Grade 3) or life-threatening pneumonitis 
• Discontinue tenalisib. Treat with systemic steroid therapy. 
Non-infectious Diarrhea 
Moderate diarrhea, responsive to antidiarrheal agents: 
• Maintain tenalisib dose. Monitor at least weekly until resolved.  
Moderate diarrhea, unresponsive to antidiarrheal agents:   
• Withhold tenalisib dose. Initiate supportive therapy with enteric 
acting steroids (e.g., budesonide). 
• Monitor at least weekly until resolved.  
• Restart tenalisib at the reduced dose level*.  
Severe diarrhea or hospitalization:  
• Withhold tenalisib dose. Initiate supportive therapy with enteric 
acting steroids (e.g., budesonide) or systemic steroids. 
• Monitor at least weekly until resolved.  
• Restart tenalisib at the reduced dose level*. 
Life threatening diarrhea:   
• Discontinue tenalisib permanently. 
Hepatic* 
Transaminitis  
Grade 1-2 Transaminitis (ALT/AST >1-3 x ULN if baseline is 
normal; 1.5 -3 x baseline if baseline is abnormal):  


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• Maintain tenalisib dose and initiate prednisone 40 mg daily.  
• Monitor AST/ALT weekly until resolved and then taper steroid.  
• Withhold tenalisib in case of development of grade 2 
transaminitis or worsening of Grade 1 transaminitis while on 
steroids.  
Grade 3 Transaminitis (ALT/AST >5–20 x ULN; >5-20 x 
baseline if baseline is abnormal):  
• Withhold tenalisib and monitor ALT/AST twice a weekly until 
Grade 1; restart tenalisib at one dose lower*.  
• Initiate prednisone 1 mg/kg in case no improvement after 
withholding tenalisib for 1 week.  
• Monitor ALT/AST twice a weekly until Grade 1; restart 
tenalisib at one dose lower* and taper steroid.  
• If no immediate response to steroids within 7 days, initiate 
mycophenolate mofetil.                                  
• Discontinue if further dose modification required at lowest dose. 
 
Grade 4 Transaminitis (ALT/AST >20 x ULN; >20x baseline if 
baseline is abnormal):  
• Tenalisib should be permanently discontinued.  
 
Bilirubin: 
Grade 2 (> 1.5-3 x ULN; >1.5-3 x baseline if baseline is abnormal):  
• Maintain tenalisib dose. Monitor at least weekly until ≤ 1x 
ULN. 
Grade 3 (> 3-10 x ULN; >3 -10 x baseline if baseline is abnormal):  
• Withhold tenalisib. Monitor at least weekly until bilirubin is ≤ 
1x ULN.  
• Restart tenalisib at one dose lower*. 
Grade 4 (> 10 x ULN; >10 x baseline if baseline is abnormal):  
• Discontinue tenalisib permanently.  
Other non-hematologic toxicities 
 
Grade 1 or 2  
 
None 
Grade 3 
Withhold tenalisib dose until toxicity Grade ≤2. Restart tenalisib at 
one dose lower* if warranted. 
Recurrence of grade 3 
toxicity 
Withhold tenalisib dose until toxicity Grade ≤2; Restart tenalisib at 
one dose lower* or discontinue treatment. 
Grade 4 
Withhold tenalisib dose until toxicity Grade ≤2; Restart tenalisib at 
one dose lower* or discontinue tenalisib. 
Recurrence of grade 4 
toxicity 
Discontinue tenalisib 
*See ‘Guidelines for dose reduction’ below.  
Note: The drug interruption and dose modification should be discussed with medical monitor. 
 
 


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Table 8 : Guidance on Tenalisib Dose reduction 
Group 
1st Dose reduction  2nd Dose reduction  
3rd Dose 
reduction  
Group 1  
(Tenalisib 800 mg BID) 
400 mg BID 
Discontinue 
- 
Group 2  
(Tenalisib 1200 mg BID) 
800 mg BID 
400 mg BID 
Discontinue  
 
 
 
8 
ASSESSMENT OF EFFICACY 
8.1 
Specification of the Efficacy Parameters 
Initial disease assessment of patients should be performed within 28 days prior to the first dose 
of study drug using computed tomography (CT) and/or magnetic resonance imaging (MRI). This 
scan will be considered as baseline scan. The PI should review baseline scan images to confirm 
the subject has measurable disease as defined in the inclusion criteria. Scan performed as part of 
routine clinical management is acceptable for use as the baseline scan if it is of diagnostic quality 
and performed within 28 days prior to the C1D1, or as approved by the medical monitor if it is 
out of window period.  
 
Subsequent scan (CT and/or MRI as applicable) should be done at C3D1 (± 7 days) and 
approximately 8 weeks thereafter (± 7 days), and/ or at the EOT and so on or as clinically 
indicated (if clinical progression is suspected). If a CR or PR is noted, confirmatory scans should 
be performed at least 4 weeks after the initial response was first documented. The scan should be 
reviewed by site investigator/radiologist/designee and tumour response will be assessed 
according to the revised Response Evaluation Criteria in Solid Tumour guideline (RECIST) 
version 1.1.[21]  
 
8.2 
Images included in the assessment. 
A CT with IV contrast will be the primary modality for assessment, unless the patient has an 
allergy to contrast that cannot be controlled with pre-medications. If patients are unable to receive 
iodinated CT contrast, the preferred imaging is non-contrast CT of the chest, and MRI of the 
abdomen and pelvis with contrast. Tumour imaging should remain consistent throughout study 
and should include those thought by investigator to best capture status of disease. For skin 
nodules, CT or MRI will be the preferred modality of assessment. Digital photography will not 
be acceptable as a method of assessment for skin lesions.  
 
8.3 
Measurable and non-measurable disease:  
Eligibility of lesions for quantitative assessment will be determined at baseline, with target 
lesions selected from the measurable lesions identified. After baseline, target lesions will 
always be assessed quantitatively, and non-target lesions will be assessed qualitatively, with 
no further evaluation of measurability according to these definitions. 
 
8.3.1 Measurable Disease 
A lesion is considered measurable, if it meets one of the measurability criteria described above.  


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• 
A lesion is considered measurable if it has a diameter of ≥ 10 mm in the axial plane on CT 
or MRI, assuming that the slice thickness is 5 mm or less. If the slice thickness is greater 
than 5 mm, the minimum size increases to two times the slice thickness.  
• 
Pathological lymph nodes are considered measurable if the short axis (greatest dimension 
perpendicular to the longest diameter) is ≥ 15 mm at baseline. 
• 
Skin nodules will be considered measurable lesion if they are assessed on CT or MRI. 
Digital photography will not be acceptable as a method of assessment for skin lesions. 
Discrete skin nodules that are not visible on CT or MRI should be considered non-
measurable lesions. 
• 
Bone lesions that are lytic or mixed lytic-blastic, which have soft tissue components seen 
on CT or MRI, and which meet size criteria above, may be measurable. 
• 
Cystic metastases may be considered measurable, but solid lesions are preferred for 
selection as target. 
 
8.3.2 Non-Measurable Disease 
A lesion is considered non-measurable, if it does not meet the measurability criteria described 
above. Example of non-measurable lesion included. 
• 
A lymph node that has a short axis diameter of 10-14 mm is considered evaluable, but not 
measurable. Nodes with a short axis diameter of < 10 mm are considered normal. 
• 
Palpable skin nodules that are not discernible using CT or MRI are considered evaluable 
but not measurable for this study.  
• 
Bone lesions that are blastic are non-measurable. 
• 
Simple cysts are considered benign by default.  
• 
Malignant ascites or pleural/pericardial effusions, lymphangitic infiltration of skin or lung, 
leptomeningeal disease, inflammatory breast disease, and infiltrative disease without clear 
borders.  
• 
Lesions seen on bone scan, or modalities other than CT or MRI (plain X-ray [with the 
exception for lung lesions], PET etc.) cannot be measured. These modalities can be used 
only to determine whether a lesion is present or absent. 
• 
Previous local treatment: A previously irradiated lesion (or lesion subjected to other local 
treatment) is non-measurable unless it has progressed since completion of previous 
treatment. 
 
8.4 
Baseline Lesion Selection and Documentation  
Target lesions will be chosen from among the measurable lesions. The lesions chosen 
should be the largest, most reproducible, and most representative of the overall disease 
distribution. 
• 
Target lesions: All measurable lesions up to a maximum of 5 lesions total, and 2 lesions 
per organ, should be selected as target lesions. Paired organs (lungs, kidneys, adrenals, 
ovaries) are considered one organ. The lymph nodes collectively are considered one organ. 
• 
Non-nodal target lesions are measured in the longest diameter in the axial plane (on CT 
or MR). Malignant lymph nodes are always measured in the short axis diameter (greatest 
dimension perpendicular to the longest diameter). The appropriate measurements for all 


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target lesions chosen at baseline will be added to produce the recorded sum of diameters, 
which will be recorded. 
• 
Other disease present at baseline should be recorded as ‘Non-target lesions’.  
 
8.5 
Assessment of Response 
The overall response for each visit is a combination of target lesion response, non-target lesion 
response, and the presence or absence of new lesions. Target lesions measurements should be 
performed in the same manner as at baseline. The sum of diameters of all target lesions must be 
calculated and compared to the baseline value and to the nadir value (the smallest value 
previously seen during the trial, which may be the same as baseline). The following special rules 
apply to lesion measurements: 
• 
If two target lesions coalesce the longest diameter measurement of the coalesced mass is 
used. If a large target lesion splits, the longest diameter of each fragment is measured, and 
the sum is used. 
• 
Measurements for target lesions that become small should continue to be recorded, as long 
as the investigator is confident in the accuracy. If a target lesion is considered to have 
completely disappeared, 0 mm should be recorded. If it is too small to measure accurately, 
but is still present, a default value of 5 mm should be recorded. 
• 
When nodal lesions decrease to < 10 mm (normal), the actual measurement should still be 
recorded. 
Target lesion response categories are defined as follows: 
• 
Complete response (CR): Disappearance of all non-nodal target lesions. Target lymph 
nodes must reduce to < 10 mm in short axis. 
• 
Partial response (PR): At least a 30% decrease in the sum of diameters of target lesions, 
compared to the sum at baseline. 
• 
Progressive disease (PD): At least a 20% increase in the sum of target lesion measurements, 
compared to the smallest sum on study (including baseline). Also, the absolute increase in 
the sum has to be at least 5 mm. 
• 
Stable disease (SD): If none of the above criteria meets. 
 
Non-target lesion response assessment is qualitative. Categories are defined as follows: 
• 
CR: Disappearance of all non-nodal non-target lesions. Non-target lymph nodes must 
reduce to < 10 mm in short axis. Note: If tumour markers are initially above the upper 
normal limit, they must normalize for a patient to be considered in complete clinical 
response. 
• 
PD: Unequivocal progression of non-target lesions, evaluated as a whole, such that it is 
clear that treatment has failed, and disease is progressing, regardless of the status of the 
target lesions. 
• 
Non-CR/Non-PD: Neither CR nor PD criteria are met. 
New lesion response is classified as present or not (“Yes” or “No”). The response is “Yes” if 
there is at least one lesion that the investigator considers unequivocal new tumour. 


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• 
Lesions that are equivocal (for example, due to small size) should not be considered new 
until they are confirmed by later scanning. Once confirmed, they can be retrospectively 
called new lesions at the time they were first seen. 
• 
A lesion identified in an area not previously scanned is considered a new lesion. 
• 
New lesions seen on nuclear medicine bone scans should be confirmed using anatomical 
imaging, whenever possible. If bone lesions are confirmed on later CT or MRI scan, 
progression should be assigned to the visit in which new lesion(s) were first seen on bone 
scan (in a manner similar to other equivocal new lesions). In the absence of structural 
confirmation, the pattern of lesions must clearly indicate metastasis, usually with at least 
two new lesions present. 
 
Overall response is determined by combining the target, non-target, and new 
lesion responses. 
 
Table 9 : Response Assessment  
Target Lesions 
Non-Target Lesions 
New Lesions 
Overall Visit 
Response 
CR 
CR 
No 
CR 
CR 
Non-CR/Non-PD or NE 
No 
PR 
PR 
Non-CR/Non-PD or NE 
No 
PR 
SD 
Non-CR/Non-PD or NE 
No 
SD 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
 
After all visits have been evaluated, the sequence of overall visit responses is used to derive best 
overall response (BOR).  
• 
BOR is defined as the best visit response recorded from the start of the treatment until 
disease progression/recurrence. 
• 
ORR: It is defined as sum of CR and PR rates  
• 
Clinical Benefit Rates: It is defined as sum of CR, PR and SD rates  
• 
PFS is measured from the time of first dose of study drug to radiographic (or tumour marker 
as applicable) documentation of disease progression or death due to any cause. 
 
9 
STATISTICAL METHOD AND CONSIDERATIONS   
9.1 
General Considerations 
This section describes the statistical methods to be used to analyze efficacy and safety. These 
methods may be revised and updated due to reasons such as regulatory requirements or need for 
further clarifications. All statistical analyses will be performed using SAS 9.1 or higher. The final 
analysis plan will be documented in a formal statistical analysis plan (SAP) that must be finalized 
before database lock. The SAP will include details on how variables will be derived, how missing 
data will be handled, and how data will be presented as well as the details on statistical methods 
to be used for safety and efficacy analyses. The final clinical study report will discuss deviations 
from the SAP, if any. 
 


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9.2 
Determination of Sample Size 
A sample size of 20 per group will provide a precision of 13% for a two-sided 90% confidence 
interval based on Exact (Clopper-Pearson) method assuming the percentage of patients without 
progression at the end of 6 month is 20%. Thus, total 40 patients (20 patients in each group) will 
be enrolled in the study. 
 
9.3 
Study Population 
The following two analysis populations are planned for this study:  
• 
Intent-to-Treat Population (ITT): The ITT is the primary analysis population and will include 
data from patients who have received at least 1 dose of study medication.  
• 
Per-Protocol (PP) Population: The PP Population is a subset of the ITT population and will 
include patients without major protocol deviations.  
 
Membership in the analysis populations will be determined before database lock. 
 
9.4 
Statistical Analysis 
9.4.1 Demographic and Baseline Characteristics 
Demographics and baseline characteristics will be summarized using descriptive statistics for 
continuous variables, and frequencies and percentages for categorical variables. 
 
9.4.2 Safety Analyses 
The safety endpoints will include: 
• 
Incidence of AEs and related AEs  
• 
Incidence of grade 3 and grade 4 AEs  
• 
Incidence of SAEs and death 
• 
Laboratory values 
• 
ECG/vital signs 
 
The safety endpoints will be listed and/or summarized by dose cohort. No inferential statistical 
analyses will be performed. The analyses of safety will be based on the frequency of adverse events 
and their severity for patients in each portion who received at least one dose of study treatment. 
Worst toxicity grades per patient will be tabulated for select adverse events and laboratory 
measurements by using NCI CTCAE criteria v5.0. 
 
9.4.3 Efficacy analyses 
The efficacy endpoints will include: 
• 
The percentage of patients without disease progression at the end of 6 months  
• 
ORR: The percentages of CR+PR will be calculated and presented along with 95% 
confidence intervals of these percentages.   
• 
CBR: The percentages of CR+PR+SD will be calculated and presented along with 95% 
confidence intervals of these percentages.   
• 
PFS: It is defined as time from the first dose of study drug to documented disease progression 
or death due to any cause. This variable will be analyzed via Kaplan-Meier methodology. 


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Additional efficacy parameters will be assessed depending on the emerging efficacy data. These 
analyses will be performed from time to time for presentation/publication purposes. 
 
9.4.4 Exploratory Analyses 
The analyses of correlative markers are exploratory and will not be used to guide treatment 
decisions. 
 
10 
ETHICAL, FINANCIAL, AND REGULATORY CONSIDERATIONS 
This trial will be conducted according to the standards of Good Clinical Practice outlined in the 
ICH E6 Tripartite Guideline, World Medical Association’s Declaration of Helsinki, local 
regulatory requirement(s), institutional research policies and procedures.  
 
All potential serious breaches must be reported to Rhizen immediately. A serious breach is a 
breach of the conditions and principles of GCP in connection with the study or the protocol, which 
is likely to affect, to a significant degree, the safety or physical or mental integrity of the subjects 
of the study or the scientific value of the study.  
 
10.1 
IRB/IEC Approval 
The trial protocol, ICF, IB, available safety information, patient documents, patient recruitment 
procedures (e.g., advertisements), information about payments (i.e., PI payments) and 
compensation available to the patients and documentation evidencing the PI’s qualifications 
should be submitted to the IRB/IEC for ethical review and approval if required by local 
regulations, prior to the trial start.   
 
The PI/Rhizen and/or designee will follow all necessary regulations to ensure appropriate, initial, 
and ongoing, IRB/IEC trial review. The PI/Rhizen (as appropriate) must submit and, where 
necessary, obtain approval from the IRB/IEC for all subsequent protocol amendments and 
changes to the informed consent document.  Investigators will be advised by Rhizen or designee 
whether an amendment is considered substantial or non-substantial and whether it requires 
submission for approval or notification only to an IRB/IEC. Safety updates will be prepared by 
Rhizen or its representative as required, for submission to the relevant IRB/IEC. 
 
10.2 
Regulatory Approval 
As required by local regulations, Rhizen will ensure all legal aspects are covered, and approval 
of the appropriate regulatory bodies obtained, prior to trial initiation. If required, Rhizen will also 
ensure that the implementation of substantial amendment to the protocol and other relevant trial 
documents happen only after approval by the relevant regulatory authorities. Safety updates will 
be prepared by the Sponsor or its representative as required, for submission to the relevant 
regulatory authority.  
 
10.3 
Insurance and Indemnity 
Details of insurance and/or indemnity will be contained within the written agreement between 
the Rhizen and PI or site. Rhizen will reimburse the subject for all study-related injuries provided 
that the injury does not arise from the subject’s misuse of the study drug or failure to follow the 
Investigator’s instructions. 
 


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10.4 
Financial Disclosure and Obligations 
Principal Investigators and Sub-Investigators are required to provide financial disclosure 
information/investigator undertaking to allow Rhizen to submit the complete and accurate 
certification or disclosure statements required as per local regulatory requirements. In addition, 
the Principal Investigator or Sub- Investigators must provide to the Sponsor a commitment to 
promptly update this information if any relevant changes occur during the course of the 
investigation and for 1 year following the completion of the study. 
 
10.5 
Informed Consent 
Informed consent is a process by which a subject voluntarily confirms his or her willingness to 
participate in a trial, after having been informed of all aspects of the trial that are relevant to the 
subject's decision to participate. Informed consent is documented by means of a written, signed 
and dated informed consent form. 
 
The informed consent form will be submitted for approval to the IRB/IEC that is responsible for 
review and approval of the trial. Each consent form must include all the relevant elements 
required by the local regulatory requirements. Translation of the informed consent form is 
allowed if necessary. 
 
Before recruitment and enrollment into the trial, each prospective candidate will be given a full 
explanation of the trial. Once the essential information has been provided to the prospective 
candidate, and the investigator is sure that the individual candidate understands the implications 
of participating in this trial, the candidate will be asked to give consent to participate in the trial 
by signing an informed consent form. A notation that written informed consent has been obtained 
will be made in the patient’s medical record. A copy of the signed informed consent form will be 
provided by the investigator to the patient.   
If an amendment to the protocol substantially alters the trial design or the potential risks to the 
patients, the patient’s re-consent to continue participation in the trial should be obtained. 
 
10.6 
Confidentiality 
10.6.1 Patient Confidentiality 
Confidentiality of patient’s personal data will be protected in accordance with national data 
protection laws, as applicable.  The study participant will be informed on the following: 
a. 
What protected health information will be collected from patients in this trial; 
b. Who will have access to that information and why;  
c. 
Who will use or disclose that information;  
d. The information collected about the research trial will be kept separate from the patient’s 
medical records, but the patient will be able to obtain the research records after the 
conclusion of the trial;  
e. 
Whether the authorization contains an expiration date;   
f. 
The rights of a research patient to revoke his or her authorization.  
 
In the event that a patient revokes authorization to collect or use his or her PHI, the investigator, 
by regulation, retains the ability to use all information collected prior to the revocation of patient 
authorization.  For patients that have revoked authorization to collect or use PHI, attempts should 


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be made to obtain permission to collect at least vital status (i.e., that the patient is alive) at the 
end of their scheduled trial period. 
 
In compliance with ICH GCP guidelines and regulatory guidance, it is a requirement that the 
investigator and institution permit authorized representatives of Sponsor, the regulatory 
authorities and the IRB/IEC direct access to review the patient’s original medical records at the 
site for verification of trial-related procedures and data.  
 
Measures to protect confidentiality include only a unique trial number and initials will identify 
patients on the eCRF or other documents submitted to Rhizen. This information, together with 
the patient’s date of birth, will be used in the database for patient identification. Patient names or 
addresses will not be entered in the eCRF or database. No material bearing a patient’s name will 
be kept on file by Sponsor. Patients will be informed of their rights within the ICF. Therefore, 
absolute confidentiality cannot be guaranteed. 
 
10.6.2 Investigator’s Responsibilities 
Medical supervision is the responsibility of the Principal Investigator. The Investigator may 
delegate day-to-day activities to a sub-investigator listed on these forms but retains overall 
responsibility for ensuring that the study is conducted properly and in accordance with the study 
protocol.  The Investigator is required to provide the Sponsor with his/her own CV and applicable 
licensure, as well as those of the personnel assuming significant responsibility in the study (e.g., 
sub-investigators). The Investigator is responsible for ensuring that the study is conducted 
according to Ethical principles that have their origins in the Declaration of Helsinki and local 
regulatory requirements and good clinical practice.  
 
10.6.3 Investigator and Staff training and Information 
Personal data of the investigators and sub-investigators may be included in the site database and 
shall be treated in compliance with all applicable laws and regulations. When archiving or 
processing personal data pertaining to the investigator or sub-investigator, the site shall take all 
appropriate measures to safeguard and prevent access to this data by any unauthorized party. 
 
All Investigators and their study personnel will receive training regarding the study procedures 
and GCP/regulations specific to the conduct of clinical trials. This training will be documented 
and will take place prior to enrollment and throughout the study as necessary. 
 
11 
RECORD RETENTION AND DOCUMENTATION OF THE TRIAL 
11.1 
Amendments to the Protocol 
Amendments to the protocol shall be planned, documented and signature authorized prior to 
implementation. If an amendment to the protocol is required, the amendment will be originated 
and documented by Rhizen. All amendments require review and approval of Rhizen and the 
Principal Investigator supporting the trial. The written amendment must be reviewed and 
submitted to the IRB/IEC at the investigator’s facility for the board’s approval. 
 
11.2 
Protocol Deviations  
The Principal Investigator is required to follow the protocol. The Investigator or designee must 
document and explain in the subject’s source documentation any deviation from the approved 


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protocol. A deviation from the protocol is an unintended and/or unanticipated departure from the 
procedures and/or processes approved by the Sponsor and the IRB/IEC and agreed to by the 
Principal Investigator. Protocol deviations will be documented by the clinical monitor throughout 
the course of monitoring visits. Principal Investigator will be notified of deviations in writing by 
the monitor. The IRB/IEC should be notified of all protocol deviations according to IRB/IEC 
reporting requirements.  
 
11.3 
Documentation Required to Initiate Trial 
Before the initiation of study, sponsor will ensure that documentation required by the local 
regulatory authorities and IRB/IEC will be in place. Documents will include, but are not limited 
to: a signed protocol, copy of regulatory and IRB/IEC approval and; current curricula vitae of the 
principal investigator; copy of signed agreement, insurance certificate, investigator undertaking 
(as applicable), IRB-approved consent form; financial disclosure forms for all investigators; site 
qualification reports, where applicable and study contract.  
 
12 
DATA HANDLING AND RECORD KEEPING  
The PI must maintain a list of appropriately qualified persons to whom he/she has delegated trial 
duties and should ensure that all persons assisting in the conduct of the trial are informed of their 
obligations. All persons authorized to make entries and/or corrections on the eCRFs are to be 
included on this document. All entries in the patient’s eCRF are to be supported by source 
documentation where appropriate. 
 
Source documents are the original documents, data, records and certified copies of original 
records of clinical findings, observations and activities from which the patient’s eCRF data are 
obtained. These can include, but are not limited to, hospital records, clinical and office charts, 
laboratory, medico-technical department and pharmacy records, diaries, microfiches, ECG traces, 
copies or transcriptions certified after verification as being accurate and complete, photographic 
negatives, microfilm or magnetic media, X-rays, and correspondence. 
 
The PI and trial staffs are responsible for maintaining a comprehensive and centralized filing 
system (Site Trial File/SSF or ISF) of all trial-related (essential) documentation, suitable for 
inspection at any time by representatives from the Sponsor and/or applicable regulatory 
authorities.  The ISF/SSF must consist of those documents that individually or collectively permit 
evaluation of the conduct of the trial and the quality of the data produced. The ISF/SSF should 
contain as a minimum all relevant documents and correspondence as outlined in ICH GCP section 
E6 and local regulatory requirements. These documents include but not limited to IB and any 
amendments, protocol and any amendments, signed ICFs, copies of completed CRFs, IEC 
approval documents, Financial Disclosure forms, patient identification lists, enrollment logs, 
delegation of authority log, staff qualification documents, laboratory normal ranges, records 
relating to the trial drug including accountability records. Drug accountability records should, at 
a minimum, contain information regarding receipt, shipment, and disposition.   
 
Each form of drug accountability record, at a minimum, should contain PI name, date drug 
shipped/received, date, quantity and batch/code, or lot number for identity of each shipment. In 
addition, all original source documents supporting entries in the eCRF must be maintained and 
be readily available. 


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The investigator/institution should maintain the trial documents as specified in Essential 
Documents for the Conduct of a Clinical Trial and as required by the applicable regulatory 
requirement(s). The investigator/institution should take measures to prevent accidental or 
premature destruction of these documents. 
 
The Investigator shall maintain adequate records of drug dispensing, medical records and any 
other trial-related records as per local regulatory requirements for no less than 2 years after the 
last marketing application has been approved by the regulatory agency; or, in the event that the 
marketing application has not been approved by local regulatory agency, for no less than 2 years 
after the last shipment / delivery of the drug for investigational use is discontinued and local 
regulatory agency has been notified of the discontinuation. 
 
To enable evaluations and/or audits from regulatory authorities or from the Sponsor or its 
representative, the investigator additionally agrees to keep records, including the identity of all 
participating patients (sufficient information to link records e.g., CRFs and medical records), all 
original, signed informed consent forms, and copies of all CRFs, SAE Reporting forms, source 
documents, detailed records of treatment disposition, and related essential regulatory 
documents.  The documents listed above must be retained by the investigator for as long as 
needed to comply with national and international regulations (generally 2 years after 
discontinuing clinical development or after the last marketing approval).  Sponsor will notify the 
investigator(s)/institutions(s) when the trial-related records are no longer required.   
 
If the investigator relocates, retires, or for any reason withdraws from the trial, both site and 
sponsor should be prospectively notified.  The trial records must be transferred to an acceptable 
designee, such as another investigator, another institution, or to sponsor.  The investigator must 
obtain the sponsor written permission before disposing of any records, even if retention 
requirements have been met.  All trial files will be maintained by the Sponsor/Sponsor 
Representative/CRO throughout the trial and will be transferred to the Sponsor at the conclusion 
of the trial. 
 
12.1 
Data Collection 
The data will be captured in electronic Case Record Form (eCRF). The CRF is clinical trials data 
management tool that provides investigational sites a standardized and validated, remote, 
electronic data capture system for the collection of clinical trial data.  All data entered on the CRF 
must be supported by and be consistent with the patient’s source documentation. All missing data 
must be explained. When a required laboratory test, assessment, or evaluation has not been done 
or an “Unknown” box is not an option on the CRF, a note should be created verifying that the 
field is “Not Done” or “Unknown”. For any entry errors made, the error(s) must be corrected, and 
a note explaining the reason for change should be provided.  
 
The principal investigator will sign and date each casebook attesting to his/her responsibility for 
the quality of all data included therein, and that the data represent a complete and accurate record 
of each subject's participation in the study.  
 


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Rhizen Pharmaceuticals AG 
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CONFIDENTIAL 
Page 60 of 66 
Clinical data management will be performed in accordance with applicable standards. Data 
cleaning procedures will be performed with the objective of removing errors and inconsistencies 
in the data which would otherwise impact on the analysis and reporting objectives, or the 
credibility of the Clinical Study Report. Adverse events, medical history and concomitant 
medications will be coded using industry standard dictionaries (MedDRA and WHO Drug).  
 
12.2 
Trial Monitoring, Auditing, and Inspecting 
The study will be monitored by the Sponsor and/or Sponsor's representatives at all stages of study 
conduct from inception to completion in accordance with current GCPs. This monitoring will be 
in the form of site visits and other communication and will include review of original source 
documents and eCRFs. The Sponsor's monitor or representative will notify the Principal 
Investigator prior to conducting any investigational site visit.  The frequency of these visits will 
depend upon the progress of the study, and will include monitoring to assess facilities and 
equipment, recruiting, record-keeping, protocol adherence, data collection, AE reporting and 
other factors. 
 
The investigator will permit trial-related monitoring, quality audits, and inspections by the 
sponsor, government regulatory authorities, the Sponsor or its representative(s) of all trial-related 
documents (e.g., source documents, regulatory documents, data collection instruments, case 
report forms). The investigator will ensure the capability for inspections of applicable trial-related 
facilities. The investigator will ensure that the trial monitor or any other compliance or QA 
reviewer is given access to all trial-related documents and trial-related facilities.   
 
Participation as an investigator in this trial implies the acceptance of potential inspection by 
government regulatory authorities, the sponsor or its representative(s). At the Sponsor’s 
discretion Source Document Verification (SDV) may be performed on all data items or a 
percentage thereof. 
 
The Investigator is responsible for notifying Rhizen in advance of an impending regulatory 
inspection. He/she may request that Rhizen provide support for preparation, if necessary, and is 
required to provide updates on the ongoing activities during the inspection and submit any 
citations/objectionable findings and is required to share any follow up responses to the outcome. 
 
12.3 
Medical Monitoring 
The sponsor will provide a medical monitor, a medical expert who advises the study investigators 
and monitors participant safety. The role of the medical monitor is to review all AEs/SAEs on a 
regular basis throughout the study, to advise the investigators on study-related medical questions 
or problems as needed, and to evaluate cumulative participant safety data and make 
recommendations regarding the safe continuation of the study.  
 
12.4 
Quality Assurance and Quality Control 
Each trial site shall be required to have Standard Operating Procedures (SOP’s) to define and 
ensure quality assurance/control processes for trial conduct, data generation & collection, 
recording of data/documentation and reporting according to the protocol, GCP and any applicable 
local, national or international regulations. 
 


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Rhizen Pharmaceuticals AG 
Version 1.0, Dated June 29, 2021 
CONFIDENTIAL 
Page 61 of 66 
13 
DISCLOSURE AND PUBLICATION POLICY 
All information provided regarding the trial, as well as information collected/documented during 
the trial, will be regarded as confidential. The Sponsor reserves the right to release literature 
publications based on the results of the trial.  Results from the trial will be published/presented 
as per the Sponsor’s publication strategy. 
 
Inclusion of the investigator in the authorship of any multi-center publication will be based upon 
substantial contribution to the design, analysis, interpretation of data, drafting and/or critically 
revising any manuscript(s) derived from the trial. The investigator acknowledges that the trial is 
part of a multi-center trial and agrees that any publication by the investigator of the results of the 
trial conducted at research site shall not be made before the first multi-center publication. In the 
event there is no multi-center publication within fifteen (15) months after the trial has been 
completed or terminated at all trial sites, and all data has been received, the investigator shall 
have the right to publish its results from the trial, subject to the notice requirements described 
herein and subject to acknowledgement of the Sponsor as appropriate.  Investigator shall provide 
the Sponsor thirty days to review a manuscript or any poster presentation, abstract or other written 
or oral material which describes the results of the trial for the purpose only of determining if any 
confidential or patentable information is disclosed thereby. If the Sponsor requests in writing, the 
investigator shall withhold any publication or presentation an additional sixty (60) days solely to 
permit the Sponsor to seek patent protection and to remove any site Confidential Information 
from all publications.  
 
14 
REFERENCES 
 
1.Lydia Xenou, Evangelia A. Papakonstanti; p110δ PI3K as a therapeutic target of solid 
tumours. Clin Sci (Lond), 2020; 134 (12): 1377–1397. 
2.Ge Z, Ding S. The Crosstalk Between Tumour-Associated Macrophages (TAMs) and Tumour 
Cells and the Corresponding Targeted Therapy. Front Oncol. 2020;10:590941. 
3.Kaneda MM, Messer KS, Ralainirina N. PI3Kγ is a molecular switch that controls immune 
suppression. Nature. 2016;539(7629):437-442. 
4.Okkenhaug K. Signalling by the phosphoinositide 3-kinase family in immune cells. Annual 
review of immunology. 2013; 31:675-704.  
5.Liu P, Cheng H, Roberts TM et al. Targeting the phosphoinositide 3-kinase (PI3K) pathway 
in cancer. Nature reviews Drug discovery. 2009;8(8):627-644. 
6.Kumar A, Fernandez-Capetillo O, Carrera AC. Nuclear phosphoinositide 3-kinase beta 
controls double-strand break DNA repair. Proc Natl Acad Sci U S A. 2011; 107:7491–6. 
7. Kao GD, Jiang Z, Fernandes AM et al. Inhibition of phosphatidylinositol-3-OH kinase/Akt 
signaling impairs DNA repair in glioblastoma cells following ionizing radiation. J Biol 
Chem. 2007; 282:21206–12.  
8.Juvekar A, Hu H, Yadegarynia S et al. Phosphoinositide 3-kinase inhibitors induce DNA 
damage through nucleoside depletion. Proc Natl Acad Sci U S A. 2016;113(30):E4338-47. 
9.Chen, F., Chen, L., Qin, Q. & Sun, X. Salt-inducible kinase 2: an oncogenic signal transmitter 
and potential target for cancer therapy. Front. Oncol. 2019; 9, 18. 


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Rhizen Pharmaceuticals AG 
Version 1.0, Dated June 29, 2021 
CONFIDENTIAL 
Page 62 of 66 
10.Bon, H. et al. Salt-inducible kinase 2 regulates mitotic progression and transcription in 
prostate cancer. Mol. Cancer Res. 2015; 13, 620–635. 
11.Tillmann Michels et.al., 2019; Salt-inducible kinase 3 facilitates tumour cell resistance 
against cytotoxic T cell attack by shifting TNF signaling from apoptosis to survival. CICON 
2019. 
12.Chen, H. et al. Salt-inducible kinase 3 is a novel mitotic regulator and a target for enhancing 
antimitotic therapeutic-mediated cell death. Cell Death Dis. 2014; 5, e1177. 
13.Amara et al. Critical role of SIK3 in mediating high salt and IL-17 synergy leading to breast 
cancer cell proliferation. PLoS ONE 12(6): e0180097. 
14.Tenalisib Investigator’s brochure. Version 12, Dated 10 May 2021. 
15.Breast Cancer. NCCN guidelines. Version 6, 2020, dated Septemebr 8, 2020 
16. Dalal Alotaibi, Suneetha Amara, Terrance L. Johnson et al. Potential anticancer effect of 
prostratin through SIK3 inhibition. Oncol Lett. 2018; 15:3252–8. 
17.Lavanya Ponnusamy , Ravi Manoharan. Distinctive role of SIK1 and SIK3 isoforms in 
aerobic glycolysis and cell growth of breast cancer through the regulation of p53 and mTOR 
signaling pathways.  Biochim Biophys Acta Mol Cell Res. 2021;1868(5):118975. 
18.A Phase I Dose Escalation Study Evaluating the Safety and Efficacy of RP6530, a dual PI3K 
δ/γ inhibitor, in Patients with Relapsed or Refractory Hematologic Malignancies (European 
study: Protocol Number RP6530-1301)  
19,A Phase I/Ib, Dose Escalation Study to Evaluate Safety and Efficacy of RP6530, a dual PI3K 
δ/γ inhibitor, in Patients with Relapsed or Refractory T-cell Lymphoma (US study: Protocol 
number RP6530-1401).  
20. An Open label, Phase I/II study to evaluate the safety and efficacy of Tenalisib (RP6530), a 
novel PI3K δ/γ dual inhibitor given in combination with a histone deacetylase (HDAC) 
inhibitor, Romidepsin in adult patients with relapsed/refractory T-cell Lymphoma (Protocol 
no. RP6530+Romidepsin-1805). Status: Ongoing 
21. Eisenhauer EA, Therasse P, Bogaerts J. et al. New response evaluation criteria in solid 
tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 ;45(2):228-47. 
 
 
 
 
 
 
 
 
 


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Rhizen Pharmaceuticals AG 
Version 1.0, Dated June 29, 2021 
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15 
APPENDICES 
        Appendix A: 
ECOG Performance Status Scale 
         
 
 
ECOG Performance Status Scale 
Grade 
Descriptions 
0 
Normal activity. Fully active, able to carry on all pre-disease performance without 
restriction. 
1 
Symptoms, but ambulatory.  Restricted in physically strenuous activity, but 
ambulatory and able to carry out work of a light or sedentary nature (e.g., light 
housework, office work). 
2 
In bed < 50% of the time.  Ambulatory and capable of all self-care, but unable to 
carry out any work activities.  Up and about more than 50% of waking hours. 
3 
In bed > 50% of the time.  Capable of only limited self-care, confined to bed or 
chair more than 50% of waking hours. 
4 
100% bedridden.  Completely disabled.  Cannot carry on any self-care.  Totally 
confined to bed or chair. 
5 
Dead 


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Rhizen Pharmaceuticals AG 
Version 1.0, Dated June 29, 2021 
CONFIDENTIAL 
Page 64 of 66 
Appendix B: Contraceptive Guidelines and Pregnancy 
Women Not of Childbearing Potential are defined as Follows 
Women are considered post-menopausal and not of child-bearing potential if they have had 12 
months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age 
appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with 
or without hysterectomy) at least six weeks ago. In the case of oophorectomy alone, only when 
the reproductive status of the woman has been confirmed by follow up hormone level 
assessment is she considered not of child bearing potential. 
Contraceptive Guidelines for Women of Child-Bearing Potential 
Women of child-bearing potential, defined as all women physiologically capable of becoming 
pregnant, must use highly effective contraception during the study and for 30 days after the last 
dose of study drug. The highly effective contraception is defined as either: 
1. True abstinence: When this is in line with the preferred and usual lifestyle of the patient. 
Periodic abstinence (e.g., calendar, ovulation, symptom-thermal, post-ovulation methods) 
and withdrawal are not acceptable methods of contraception. 
2. Sterilization:  have had surgical bilateral oophorectomy (with or without hysterectomy) or 
tubal ligation at least six weeks ago.  In case of oophorectomy alone, only when the 
reproductive status of the woman has been confirmed by follow up hormone level 
assessment. 
3. Male partner sterilization (with the appropriate post-vasectomy documentation of the 
absence of sperm in the ejaculate). For female patients on the study, the vasectomized male 
partner should be the sole partner for that patient. 
4. Use of a combination of any two of the following (a+b): 
a. Placement of an intrauterine device (IUD) or intrauterine system (IUS). 
b. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or   
cervical/vault 
caps) 
with 
spermicidal 
foam/gel/film/cream/vaginal 
suppository/pessary. 
The following are unacceptable forms of contraception for women of childbearing potential:  
• 
Oral contraception, injected or implanted hormonal. 
• 
IUD progesterone T  
• 
Female condom  
• 
Natural family planning (rhythm method) or breastfeeding  
• 
Fertility awareness  
• 
Withdrawal  
• 
Cervical shield 
Women of child-bearing potential must have a negative serum or urine pregnancy test ≤ 72 
hours prior to initiating treatment. 
Pregnancies 


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Rhizen Pharmaceuticals AG 
Version 1.0, Dated June 29, 2021 
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To ensure patient safety, each pregnancy in a patient on study treatment must be reported to 
Rhizen Pharmaceuticals AG within 24 hours of learning of its occurrence. The pregnancy should 
be followed up for 3 months after the termination of the pregnancy to determine outcome, 
including spontaneous or voluntary termination, details of the birth, and the presence or absence 
of any birth defects, congenital abnormalities, or maternal and/or newborn complications. 
Consent to report information regarding these pregnancy outcomes should be obtained from the 
mother. 
Pregnancy is not considered a SAE. Initial and follow up information should be recorded on a 
Clinical Study Pregnancy Form and reported by the investigator to Rhizen Pharmaceuticals AG. 
Pregnancy follow-up should be recorded on the same form and should include an assessment of 
the possible relationship to the investigational drugs to any pregnancy outcome will also be 
captured on the pregnancy form. Any SAE experienced during pregnancy must be reported on 
the SAE Report Form. 
Pregnancy outcomes must be collected for the female partners of any males who took study 
treatment in this study. Consent to report information regarding these pregnancy outcomes 
should be obtained from the mother. 


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Rhizen Pharmaceuticals AG 
Version 1.0, Dated June 29, 2021 
CONFIDENTIAL 
Page 66 of 66 
Appendix C: Cytokines/Chemokines and Tumour Biopsy 
• Serum samples will be assessed for following cytokines/chemokines at the screening (baseline) 
and at Cycle 3 Day 1:  
Assessment  
Tissue sample  
Exploratory marker 
Cytokines/Chemokines  
Serum  
CCL2/JE/MCP-1, CCL3/MIP-
1alpha, CCL4/MIP-1 beta, 
CCL11/Eotaxin,CCL13/MCP-
4, CCL17/TARC, 
CCL22/MDC,CCL26/Eotaxin-
3, CXCL9/MIG, CXCL10/IP-
10/CRG-2, IL-8/CXCL8 
IFN-γ, IL-1β, IL-2, IL-4, IL-6, 
IL-8,IL-10, IL-12p70, IL-13, 
TNF-α 
Gene expression by RNA 
sequencing  
Tissue biopsy sample 
Approx. 21,000 genes 
 
 

SAP_001.pdf: 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 1 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
 
 
Protocol No. RP6530-2101 
 
A Phase II, Multi-center, Randomized, Open label, two arm Study to Assess the Efficacy and 
Safety of Tenalisib (RP6530), a PI3K δ/γ and SIK3 Inhibitor, in patients with Locally 
Advanced or Metastatic Breast Cancer 
 
Statistical Analysis Plan 
 
Prepared for: 
Rhizen Pharmaceuticals AG 
 
 
Final Version 1.0 Date 12MAY2023 
 
 
Prepared by: 
Labcorp Drug Development 
Clinical Development Commercialization Services 
Princeton, NJ  
VERSION HISTORY OF IMPLEMENED PLANS  
Version 
Date 
Revision Author 
Comments 
NA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 2 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
 
 
Table of Contents 
 
 
 
1. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .................................................................... 3 
2. 
INTRODUCTION ................................................................................................................................................. 4 
3. 
STUDY OBJECTIVES ........................................................................................................................................ 4 
4. 
STUDY DESIGN .................................................................................................................................................. 5 
4.1 GENERAL DESIGN .................................................................................................................................................. 5 
4.2 DISCUSSION OF STUDY DESIGN ............................................................................................................................ 5 
4.3 METHOD OF ASSIGNMENT OF PATIENTS TO TREATMENT GROUPS .................................................................... 5 
4.4 BLINDING................................................................................................................................................................. 5 
4.5 DETERMINATION OF SAMPLE SIZE ........................................................................................................................ 6 
5. 
CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED ANALYSES ........................................ 6 
5.1 CHANGES IN THE CONDUCT OF THE STUDY ......................................................................................................... 6 
5.2 CHANGES FROM THE ANALYSES PLANNED IN THE PROTOCOL ........................................................................... 6 
6. 
BASELINE, EFFICACY AND SAFETY EVALUATIONS ............................................................................. 6 
6.1 SCHEDULE OF EVALUATIONS................................................................................................................................. 6 
6.2 TIME POINT ALGORITHMS ...................................................................................................................................... 8 
6.2.1 Relative Day.................................................................................................................................................. 8 
6.2.2 Windows ........................................................................................................................................................ 9 
6.3 BASELINE ASSESSMENTS ...................................................................................................................................... 9 
6.4 EFFICACY VARIABLES ............................................................................................................................................ 9 
6.4.1 Primary Efficacy Variable ......................................................................................................................... 9 
6.4.2 Secondary Efficacy Variables .................................................................................................................. 9 
6.4.3 Additional Efficacy Variables................................................................................................................. 10 
6.5 DRUG CONCENTRATION MEASUREMENTS AND PHARMACOKINETIC PARAMETERS ......................................... 10 
6.5.1 Handling of Pharmacokinetic Parameter Outliers............................................................................ 10 
6.6 SAFETY ASSESSMENTS ....................................................................................................................................... 10 
6.6.1 Duration of Treatment Exposure and Compliance to Study Treatment ..................................... 10 
6.6.2 Clinical Laboratory Evaluations ............................................................................................................ 11 
6.6.3 Other Observations Related to Safety ................................................................................................. 11 
• 
Vital Signs ...................................................................................................................................................................................... 11 
• 
Electrocardiogram (ECG) ............................................................................................................................................................ 11 
• 
Physical Examination ................................................................................................................................................................... 11 
• 
ECOG Performance Status ......................................................................................................................................................... 11 
• 
Medical and Surgical History ....................................................................................................................................................... 11 
• 
Prior and Concomitant Medications ........................................................................................................................................... 11 
6.7 PHARMACODYNAMICS PARAMETERS .................................................................................................................. 11 
7. 
STATISTICAL METHODS ............................................................................................................................... 11 
7.1 GENERAL METHODOLOGY ................................................................................................................................... 11 
7.2 ADJUSTMENTS FOR COVARIATES ........................................................................................................................ 12 
7.3 HANDLING OF DROPOUTS OR MISSING DATA .................................................................................................... 12 
7.4 INTERIM ANALYSES AND DATA MONITORING ...................................................................................................... 13 
7.5 MULTI-CENTRE STUDIES AND POOLING OF CENTRES ....................................................................................... 13 
7.6 MULTIPLE COMPARISONS/MULTIPLICITY ............................................................................................................ 13 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 3 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
7.7 USE OF AN “EFFICACY SUBSET” OF PATIENTS ................................................................................................... 14 
7.8 ACTIVE-CONTROL STUDIES INTENDED TO SHOW EQUIVALENCE ..................................................................... 14 
7.9 EXAMINATION OF SUBGROUPS ............................................................................................................................ 14 
8. 
STATISTICAL ANALYSIS .............................................................................................................................. 14 
8.1 DISPOSITION OF PATIENTS .................................................................................................................................. 14 
8.2 PROTOCOL DEVIATIONS ...................................................................................................................................... 14 
8.3 ANALYSIS POPULATIONS ..................................................................................................................................... 14 
8.3.1 Safety Population ...................................................................................................................................... 14 
8.3.2 Intent-to-Treat (ITT) Population ............................................................................................................. 14 
8.3.3 Protocol (PP) Population ........................................................................................................................ 15 
8.3.5 Pharmacokinetics (PK) population ...................................................................................................... 15 
8.4 DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS ............................................................................... 15 
8.5 PRIOR AND CONCOMITANT THERAPY ................................................................................................................. 15 
8.6 PRIOR THERAPIES ................................................................................................................................................ 16 
8.7 ANALYSIS OF EFFICACY PARAMETERS ............................................................................................................... 16 
8.7.1 Analysis of Primary Efficacy Variable ................................................................................................. 16 
8.7.2 Analysis of Secondary Efficacy Variables ......................................................................................... 17 
8.7.3 Analysis of Pharmacokinetic Variables .............................................................................................. 18 
8.7.4 Subgroup Analyses .................................................................................................................................. 18 
8.8 ANALYSIS OF SAFETY .......................................................................................................................................... 18 
8.8. 1 Duration of Treatment Exposure and Compliance to Study Treatment .................................... 18 
• 
Duration of Treatment .................................................................................................................................................................. 18 
• 
Measurements of Treatment Compliance ................................................................................................................................. 18 
8.8.2 Adverse Events ......................................................................................................................................... 19 
8.8.3 Clinical Laboratory Evaluations ............................................................................................................ 20 
8.8.4 Other Observations Related to Safety ................................................................................................. 21 
• 
Vital Signs .................................................................................................................................................................................... 21 
• 
Physical Findings ....................................................................................................................................................................... 21 
• 
Electrocardiogram ...................................................................................................................................................................... 21 
• 
Medical and Surgical history ................................................................................................................................................... 21 
• 
ECOG ............................................................................................................................................................................................. 21 
• 
Additional listings ...................................................................................................................................................................... 21 
8.9 PHARMACODYNAMICS .......................................................................................................................................... 22 
9. 
COMPUTER SOFTWARE ............................................................................................................................... 22 
10. 
REFERENCES .................................................................................................................................................. 22 
11. 
APPENDICES .................................................................................................................................................... 22 
12. 
TABLE SHELLS AND SPECIFICATIONS ................................................................................................... 22 
 
 
 
1. LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
Table 1: Abbreviations and Definitions of Terms 
 
 
Add or remove as necessary 
AE(s) 
adverse event(s) 
b.i.d. 
twice daily 
BUN 
blood urea nitrogen 
CI 
confidence interval 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 4 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
CR 
Complete response 
CRF 
case report form 
ECG 
electrocardiogram 
FDA 
Food and Drug Administration 
HDL 
high-density lipoprotein 
HEENT 
head, eyes, ears, nose, and throat 
HIV 
human immunodeficiency virus 
ICH 
International Council for Harmonisation 
IRB/IEC 
Institutional Review Board/Independent Ethics Committee 
ITT 
intent-to-treat 
LDH 
lactate dehydrogenase 
LDL 
low-density lipoprotein 
MedDRA 
medical dictionary for regulatory activities 
mg 
milligram 
n 
number of patients 
PR 
Partial response 
QTc 
Q-T interval corrected for heart rate 
QTc-F 
Q-T interval corrected for heart rate using Frederica’s formula 
SAE 
serious adverse event 
SAS 
(statistical analysis software) 
SD 
Stable disease 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
WHO 
World Health Organisation 
 
 
 
2. INTRODUCTION 
 
This statistical analysis plan (SAP) contains definition of analysis population(s), derived variables and 
statistical methods for efficacy and safety analysis. 
 
The SAP is written based on the following documentation: 
Document 
Date 
Version 
Protocol 
29June2021 
1.0 
eCRF 
24Sep2021 
1.0 
eCRF 
16June2022 
5.0 
 
Breast cancer is the most common cancer diagnosed in women and is the second leading cause of cancer-
related deaths. Based on these pre-clinical evidences with tenalisib and clinical evidences from other PI3K 
inhibitors, it is proposed that tenalisib has the potential to treat the patients with locally advanced and 
metastatic breast cancer. 
 
The objective of the study is to assess the anti-tumour activity along with safety and efficacy of tenalisib at 
two different doses in order to identify the optimal dose that shows signal of clinical efficacy with an 
acceptable safety profile. This dose can be thus taken ahead for further development. Doses of 800 mg 
BID and 1200 mg BID are proposed in this Phase II study. 
 
 
3. STUDY OBJECTIVES 
Primary Objective 
To assess the anti-tumour activity of tenalisib in patients with locally advanced or metastatic breast cancer. 
Secondary Objective 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 5 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
To evaluate the safety and tolerability of tenalisib. 
Exploratory Objective 
Changes in serum cytokines/chemokines and tumour tissue gene expression post treatment with tenalisib. 
 
4. STUDY DESIGN 
 
4.1 General Design 
This is a Phase II, randomized, open label study, designed to evaluate the preliminary efficacy and safety of 
tenalisib at two dose levels (800 mg BID and 1200 mg BID) in 40 patients with locally advanced or metastatic 
breast cancer. Twenty patients each, will be enrolled in Group 1 (Tenalisib 800 mg BID) and Group 2 
(Tenalisib 1200 mg BID). Both groups will run in parallel. The expected duration of patient participation in the 
study will be approximately 24 months, unless the patient is discontinued from the study due to disease 
progression, drug toxicity or consent withdrawal. 
 
4.2 Discussion of Study Design 
The study design flow chart is as follows: 
 
 
4.3 Method of Assignment of Patients to Treatment Groups 
This is a randomized, open label study. Eligible patients will be randomized to one of the two groups (Group 
1: Tenalisib 800 mg BID and Group 2: Tenalisib 1200 mg BID) in 1:1 ratio based on the central randomization 
list generated by a validated software. 
 
4.4 Blinding 
Blinding is not applicable as this is an open label study. 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 6 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
4.5 Determination of Sample Size 
A sample size of 20 per group will provide a precision of 13% for a two-sided 90% confidence interval based 
on Exact (Clopper-Pearson) method assuming the percentage of patients without progression at the end of 
6 months is 20%. Thus, a total of 40 patients (20 patients in each group) will be enrolled in the study. 
 
5. 
CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED ANALYSES 
 
5.1 Changes in the Conduct of the Study 
The study was planned to administer tenalisib to all patients until disease progression or unacceptable toxicity 
for a maximum duration of 24 months. However this was changed and the study was closed earlier before 
all patients in the study showed disease progression. . 
 
5.2 Changes from the Analyses Planned in the Protocol 
There were no changes in the analysis planned in the protocol of the study at the time of preparing this 
statistical analysis plan. 
 
6. 
BASELINE, EFFICACY and Safety EVALUATIONS 
 
6.1 Schedule of Evaluations 
The assessments to be conducted at each scheduled visit are displayed in the following table.  
 
 
Table 1 
Assessments Conducted at each Scheduled Visit  
 
Table 5 : Schedule of Events  
Cycle  
Screening  C1  
C2  
C3  Monthly 
visits  
(C4 
onward 
up to 2 
year)19  
Efficacy 
Visits  
(C5, C7, 
C9… up 
to 2 
year)20  
EOT21  EOS22  
Day  
D-28 to 0  
D1  D15  D1  D15  D1  D1  
D1  
-  
-  
Window period  
-  
 
±1  
±1  ±3  
±3  ±3  
±7  
+7 
+30 
Study Days  
D-28 to 0  
1  
15  
29  43  
57  -  
-  
-  
-  
Informed Consent1  
X  
-  
-  
-  
-  
-  
-  
-  
-  
-  
Demographics2  
X  
-  
-  
-  
-  
-  
-  
-  
-  
-  
Medical history3  
X  
X  
-  
-  
-  
-  
-  
-  
-  
-  
Vitals4  
X  
X  
X  
X  
X  
X  
X  
-  
X  
-  
Height and weight5  
X  
X  
X  
X  
X  
X  
X  
-  
X  
-  
Physical examination6  X  
X  
X  
X  
X  
X  
X  
-  
X  
-  
ECOG Performance 
Status  
X  
X  
-  
X  
-  
-  
X  
-  
X  
-  
Complete blood 
count7  
X  
X  
X  
X  
X  
X  
X  
-  
X  
-  
Chemistry panel I8  
X  
X  
X  
X  
X  
X  
X  
-  
X  
-  
Chemistry panel II9  
X  
X  
-  
X  
-  
X  
X  
-  
X  
-  


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 7 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
HIV, HBV, HCV status  X  
-  
-  
-  
-  
-  
-  
-  
-  
-  
PT and INR10  
X  
X  
-  
X  
-  
X  
-  
-  
X  
-  
Cytokines/chemokines 
analysis11  
X  
-  
-  
-  
-  
X  
-  
-  
-  
-  
Urinalysis (routine)  
X  
X  
X  
X  
X  
X  
X  
-  
X  
-  
Pregnancy test12  
X  
X  
-  
-  
-  
-  
-  
-  
-  
-  
12-lead ECGs13  
X  
X  
-  
X  
-  
X  
-  
-  
X  
-  
Tumour biopsy14  
X  
-  
-  
-  
-  
X  
-  
-  
-  
-  
Radiological 
assessment (CT 
and/or MRI)15  
X  
-  
-  
-  
-  
X  
-  
X  
X  
-  
Bone scan16  
X  
-  
-  
-  
-  
-  
-  
-  
-  
-  
Drug Dispensing17  
-  
X  
-  
X  
-  
X  
X  
-  
-  
-  
Tenalisib 
administration18  
-  
X  
X  
X  
X  
X  
X  
-  
-  
-  
Drug compliance  
-  
X  
X  
X  
X  
X  
X  
-  
X  
-  
AE evaluation  
X  
X  
X  
X  
X  
X  
X  
-  
X  
X  
SAE evaluation  
X  
X  
X  
X  
X  
X  
X  
-  
X  
X  
Concomitant 
medication  
X  
X  
X  
X  
X  
X  
X  
-  
X  
X  
Footnotes: 
1. Patient should be re-consented, if informed consent is obtained > 30 days prior to the initiation of trial 
treatment. The first day of tenalisib administration will be considered as C1D1. 
2. Demographic profile will include age, sex and race. 
3. Detailed history will be taken at screening that includes history of cancer, past history, no of prior therapies 
and prior medication (in last 4weeks); and other medical history. Patient’s medical record must include prior 
treatments received, dates of administration, response to prior therapies and date of progression. 
4. Vitals will include pulse (sitting/supine); blood pressure (sitting/supine); respiratory rate and oral 
temperature. Vitals will be done at pre-dose at all visits. 
5. Weight will be measured at all visits. Height to be measured at screening only. 
6. Physical examination will include systemic examination (General Appearance, HEENT, neck, 
cardiovascular, lungs, abdomen, extremities, neurological, skin, and musculoskeletal). Complete physical 
examination will be done at screening visit. At subsequent visits, abbreviated examination will be done 
depending on the assessment of tumour. 
7. This will include Hb, complete blood count, total leucocyte and differential count and platelet count. 
Additional investigations will be performed if clinically indicated. Hematology must be done ≤ 7 days prior to 
initiation of treatment. However, if these initial examinations are obtained within 72 hours of C1D1; they do 
not have to be repeated. 
8. Chemistry Panel I include blood glucose, albumin, total protein, total bilirubin, ALP, AST, ALT, GGT, LDH, 
urea or blood urea nitrogen, creatinine, sodium, potassium, chloride, calcium, phosphorus. These tests must 
be done ≤ 7 days prior to initiation of treatment. However, if these initial examinations are obtained within 72 
hours of C1D1; they do not have to be repeated. These tests will be performed at supplementary visits if 
clinically indicated. 
9. Chemistry Panel II includes total cholesterol, TG, LDL, HDL, T3, T4 and TSH. These tests must be done 
≤ 7 days prior to initiation of treatment. However, if these initial examinations are obtained within 72 hours of 
C1D1; they do not have to be repeated. These tests will be performed at supplementary visits if clinically 
indicated. 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 8 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
10. The tests must be done ≤ 7 days prior to initiation of treatment. However, if initial examination is obtained 
within 72 hours of C1D1; this does not have to be repeated. This test will be performed at supplementary 
visits if clinically indicated. 
11. Blood will be collected in all patients for serum cytokine/chemokine estimation at screening (baseline) 
and at C3D1. 
12. This is required for women of child-bearing potential. A serum pregnancy test will be performed at 
screening and 72 hours prior to dosing. Urine pregnancy test will be performed at other visits as indicated. 
13. ECGs will be performed at screening and C1D1 pre-dose to establish baseline cardiac activity. Additional 
ECGs will be obtained if clinically indicated. All ECGs will be performed on local equipment. 
14. A tumour biopsy will be performed in 10-12 patients who have consented for the biopsy. The biopsy will 
be done after eligibility confirmation prior to the first dose on C1D1. A second tumour biopsy sample will be 
taken at C3D1. 
15. CT and/ or MRI will be performed at the time of screening within 28 days of screening. Disease will be 
re-assessed at C3D1 (± 7 days) and approximately 8 weeks thereafter (± 7 days), and/or at the EOT (not 
required if done within last 28 days) and/or as clinically indicated (if clinical progression is suspected). If a 
CR or PR is noted, confirmatory scans should be performed at least 4 weeks after the initial response was 
first documented. Tumour imaging should remain consistent throughout the study and should include those 
thought by investigator to best capture status of disease. (Baseline scan, if already available as SOC within 
28-days of screening is accepted as part of study protocol). Any other sites at which new disease is suspected 
should also be appropriately imaged. 
16. Bone scan will be done at the baseline when progression in bone is suspected. Bone scans need to be 
repeated only when complete response is reported in target disease or when progression in bone is 
suspected. 
17. Tenalisib will be dispensed in a HDPE container having 30 tablets of tenalisib. 
18. Tenalisib will be administered orally twice a day in 28-days of cycle. Tenalisib will be continued in patients 
experiencing clinical benefit for 24 months unless progression of disease or toxicity is observed warranting 
discontinuation of therapy. 
19. All visits will be done monthly from Cycle 3 onwards for 24 months (e.g. C4, C5, C6…. C26). 
20. All visits for efficacy assessments will be done at 8-weekly intervals (± 7 days) for 24 months (e.g.C5, 
C7…. C26). 
21. All patients will undergo the end-of-treatment (EOT) assessments within 7 days after last dose of study 
drug or discontinuation. 
22. Patients must be followed telephonically for adverse events for 30 calendar days after the last dose of 
study drug. 
6.2 Time Point Algorithms 
6.2.1 Relative Day 
The date of first dose of study drug will be considered relative day 1, and the day before the first dose of 
study drug will be relative day -1. Relative days will be calculated as follows only when the full assessment 
date is known (i.e., partial dates will have missing relative days): 
For days on or after the first dose of study drug: 
Date of Assessment – Date of First Dose of Study Drug + 1. 
 
For days before the first dose of study drug: 
Date of Assessment – Date of First Dose of Study Drug. 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 9 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
6.2.2 Windows 
For the purpose of statistical analysis, the visit numbers will be recalculated in terms of study days since the 
first day of the trial medication, as illustrated in the following table: 
 
Analysis Windows 
 
Visit 
Scheduled Study Day 
Visit Window for Analysis (Days) 
Screening 
-28 to 0 
- 
C1D1 
1 
0 
C1D15 
15 
14 – 16 
C2D1 
29 
28 – 30 
C2D15 
43 
40 – 46 
C3D1 
57 
54 – 60 
Monthly visits (C4 onward up to 
2 year) 
- 
±3 
Efficacy Visits (C5, C7, C9… up 
to 2 year) 
- 
±7 
EOT 
- 
+7 
EOS 
- 
+30 
EOT=End of Treatment; EOS= End of study; C1D1=Cycle 1 Day 1. 
 
6.3 Baseline Assessments 
The baseline measurement is the last predose measurement taken before first study treatment dose. 
 
The following baseline assessments will be conducted prior to initial study drug administration: 
• 
Age 
• 
Race  
• 
Height 
• 
Weight 
• 
Menopausal Status 
• 
Medical History 
• 
Physical examination 
• 
ECOG Performance Status 
• 
Laboratory tests 
• 
Pregnancy test 
• 
12-lead ECGs 
• 
Radiological assessment 
 
 
6.4 Efficacy Variables 
All efficacy parameters will be summarized using ITT and PP analysis set. 
 
6.4.1 Primary Efficacy Variable 
The primary efficacy variable is the percentage of patients without disease progression at the end of 6 
months i.e. 180 days: 
Percentage = (patients without disease progression/total number of patients) *100. 
 
6.4.2 Secondary Efficacy Variables 
The best overall response is defined as the best visit response recorded from the start of the treatment until 
disease progression/recurrence. This data will be summarized using frequency and percentage for 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 10 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD) for 
each treatment group. 
 
• 
Overall Response Rate (ORR): The percentages of CR+PR will be calculated and presented along 
with 95% confidence intervals of these percentages. 
• 
Clinical Benefit Rate (CBR): The percentages of CR+PR+SD>=24 weeks will be calculated and 
presented along with 95% confidence intervals of these percentages. 
• 
Progression Free Survival (PFS): It is defined as time from the first dose of study drug to 
documented disease progression or death due to any cause. This variable will be analyzed via 
Kaplan-Meier methodology. 
 
6.4.3 Additional Efficacy Variables 
Duration of Treatment Exposure: Duration of treatment exposure is defined as the time from first 
dose to last dose of drug.  
 
Duration of Response: Duration of response (DoR) is defined as the time from the first occurrence of 
partial or complete response to disease progression or death in patients who achieve complete or 
partial response. For patients who neither progress nor die, the duration of response will be 
censored on the last date the patient is known to be radiologically progression free. 
 
Duration of clinical benefit: Duration of clinical benefit (DoCB) is defined as the time from the first 
dose of study drug to disease progression or death in patients who achieve complete response, 
partial response, or stable disease for 24 weeks or longer. For patients who neither progress nor 
die, the duration of response will be censored on the last date the patient is known to be 
radiologically progression free. 
 
 
Proportion of patients with 6-Month and 1-year PFS. 
PFS rate at 6-months or at 1-year: Proportion of patients who remained alive and progression-free 
at 6 months or at 1-Year 
 
 
6.5 Drug Concentration Measurements and Pharmacokinetic Parameters 
Not Applicable. 
 
6.5.1 Handling of Pharmacokinetic Parameter Outliers 
Not Applicable. 
6.6 Safety Assessments 
The safety endpoints will be listed and/or summarized by dose cohort. 
• 
Number of Adverse events (AE),  
• 
Number of Grade 3/4 AEs,  
• 
Death  
• 
Number of Serious adverse events (SAE) evaluated and graded using NCI-CTCAE Version 5.0. 
 
6.6.1 Duration of Treatment Exposure and Compliance to Study Treatment 
Treatment compliance and the treatment exposure will be summarized descriptively (n, mean, median, 
standard deviation, minimum and maximum values) and will also be listed. 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 11 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
6.6.2 Clinical Laboratory Evaluations 
Change from baseline for each visit will be defined as the visit value minus the baseline visit value.  
 
6.6.3 Other Observations Related to Safety 
• 
Vital Signs 
Absolute value of vital signs parameters will include summaries for systolic and diastolic blood pressure, 
temperature, pulse, respiratory rate and weight.  
Vitals will be done prior to the administration of study treatments, at the time points specified in schedule of 
events. 
• 
Electrocardiogram (ECG) 
Absolute value of ECG parameters will include summaries for heart rate, PR, QRS, QT, and QTcF 
intervals.  
 
• 
Physical Examination 
 
The investigator/qualified designee will perform a complete physical exam during the screening period and 
as defined in Schedule of Events. Physical examination will include systemic examination (General 
Appearance, HEENT, neck, cardiovascular, lungs, abdomen, lymph nodes, genitourinary (as applicable), 
extremities, neurological, skin, and musculoskeletal). Physical examination also includes measurement of 
accessible nodes and the size of the spleen and liver. 
 
• 
ECOG Performance Status 
 
• 
Medical and Surgical History 
 
• 
Prior and Concomitant Medications 
 
6.7 Pharmacodynamics Parameters 
 
Not Applicable. 
 
 
7. 
STATISTICAL METHODS 
 
7.1 General Methodology 
 
 All statistical analyses will be performed using SAS 9.4 or higher. 
Continuous data will be summarized using descriptive statistics (number of patients (n), mean, standard 
deviation (SD), median, minimum, and maximum). Summary statistics for continuous measures will be 
provided for baseline, the actual measurements at each visit, and where appropriate, the change from 
baseline measurements to each visit. Discrete data will be summarized using frequency counts and 
percentages and where appropriate, the 95% Confidence Intervals (CIs) will be presented.  
 
When count data are presented, the percentage will be suppressed when the count is zero in order to draw 
attention to the non-zero counts. A row denoted “Missing” will be included in count tabulations where 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 12 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
necessary to account for dropouts and missing patients. Unless otherwise specified, the denominator for 
percentages will be the number of patients with a non-missing assessment in a given treatment group 
within the analysis population of interest. 
 
All the patient data will be summarized by treatment group and overall. 
 
The following sub-group analysis will be performed only for demographics, baseline characteristics and 
efficacy tables: 
 
1. de novo metastasis, recurrent (locoregional/distal) metastasis and Overall 
 
 
Patient listings of all data from the case report forms (CRFs) as well as any derived variables will be 
presented.  
 
 
 
7.2 Adjustments for Covariates 
Not applicable to this study  
 
7.3 Handling of Dropouts or Missing Data 
 
Missing results/events will not be imputed. Imputations will be done for missing dates as follows.  
 
Missing Dates for Adverse Events and Concomitant Medications 
 
Adverse events and concomitant medications with completely or partially missing assessment dates will 
have imputation performed as explained below for the purposes of calculation of durations or relativity to 
study medication. 
 
For the end of a concomitant medication or adverse event: 
 
• 
If only Day of end date is missing: 
The last date of the month and year reported or the date of the final contact with the patient, whichever is 
earlier, will be used as the end date. 
 
• 
If Day and Month of end date are missing: 
The last date of year i.e. December 31 of the year reported or the date of the last study contact with the 
patient, whichever is earlier, will be used as the end date. 
 
• 
If Year of end date or complete end date is missing: 
If the year of end of medication/event is missing or end date is completely missing, then no end date will be 
imputed. 
 
For the start of a concomitant medication or adverse event: 
 
• 
If only Day of start date is missing: 
o If the start year and month of medication/event are the same as that for the first dose date, 
then following approach will be used: 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 13 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
▪ 
If the end date of medication/event is NOT before the first dose date or end date of 
medication/event is completely missing, then impute the start day as the day of first 
dose date 
▪ 
Otherwise, impute the start day as 1. 
 
o If the start year and month of medication/event are NOT same as that for the first dose date, 
then 
▪ 
Impute the start day as 1. 
▪ 
 
• 
If Day and Month of start date are missing: 
o If start year of medication/event is same as first dose year, then following approach will be 
used: 
i. 
For medication, impute the start Month as January and the Day as 1 
ii. 
For adverse event, 
• 
If the end date of event is NOT before the first dose date or end date of event 
is completely missing, then impute the start Month and Day as the Month and 
Day of first dose date; 
• 
Otherwise, impute the start Month as January and the Day as 1. 
o If start year of medication/event is NOT same as first dose year, then 
• 
Impute start Month as January and the Day as 1. 
 
• 
If Year of start date or complete start date is missing: 
 
If the year of start of medication/event is missing or start date is completely missing, then no start date 
will be imputed. 
 
Missing Dates for Efficacy Endpoints 
For time-to-event endpoint if the date is completely missing, no imputation will be performed. 
However, the incomplete/partial dates will be handled following the general conventions as detailed for 
adverse events and concomitant medications. 
 
Missing dates for Primary Diagnosis/Prior therapy 
 
Partial Primary diagnosis and prior therapy dates will have imputation performed as explained below for the 
purposes of calculation of relativity to study medication. 
 
• 
If only Day is missing, impute the day 1 
• 
If Day and Month are missing, impute the Month as January and the Day as 1. 
• 
If the year of primary diagnosis is missing or the date of primary diagnosis is completely missing, 
then no date will be imputed. 
 
7.4 Interim Analyses and Data Monitoring 
No interim analysis or data monitoring is planned for this study. 
 
7.5 Multi-Centre Studies and Pooling of Centres 
Data from all the centres will be pooled together for the analysis. 
 
 
7.6 Multiple Comparisons/Multiplicity 
Not applicable. 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 14 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
 
7.7 Use of an “Efficacy Subset” of Patients 
Not applicable to this study. 
 
7.8 Active-Control Studies Intended to Show Equivalence 
Not applicable to this study. 
 
 
7.9 Examination of Subgroups 
 
The following sub-group analysis will be performed only for demographics, baseline characteristics and 
efficacy tables: 
 
1. 
de novo metastasis, recurrent (locoregional/distal) metastasis and Overall. 
 
8. 
STATISTICAL ANALYSIS 
8.1 Disposition of Patients 
A tabular presentation of the patient disposition data will be provided by treatment group and overall. It will 
include the number of patients screened, enrolled, randomized, completed cycle 3, 6, 9,12 and 15, as well 
as the number of dropouts, with reasons for discontinuation, number in each population sets, number of 
patients with dose reductions or interruptions (if applicable), number patients with discontinuations due AEs 
etc. All patients data will be used for this report. 
 
8.2 Protocol Deviations 
A full list of protocol deviations for the study report will be compiled prior to database closure. All deviations 
will be reviewed by the Medical monitor prior to database closure. Each deviation will be categorized as 
major and minor and a decision will be taken by medical monitor whether to include the patient in a PP 
analysis population. 
 
Protocol deviations will be presented as number and percentage of patients with minor and major 
deviations in the study for each treatment group and overall for all the  patients in Safety analysis set. This 
data will also be listed as appropriate. 
 
8.3 Analysis Populations 
The following analysis populations are planned for this study: 
8.3.1 Safety Population 
The Safety Population will include all patients who receive at least 1 dose of the study medication. This 
population will be used for safety analysis. 
 
8.3.2 Intent-to-Treat (ITT) Population 
The ITT is the primary analysis population and will include data from patients who have received at least 1 
dose of study medication. This population will be used for efficacy assessment. Per definition, the ITT and 
Safety population are similar in this study. 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 15 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
8.3.3 Protocol (PP) Population 
The PP Population is a subset of the ITT population and will include patients without major protocol 
deviations. This population will also be used for efficacy assessment. 
 
A deviation from the protocol is an unintended and/or unanticipated departure from the procedures and/or 
processes approved by the Sponsor and the IRB/IEC and agreed to by the Principal Investigator. Protocol 
deviations will be documented by the clinical monitor throughout the course of monitoring visits. Principal 
Investigator will be notified of deviations in writing by the monitor. The IRB/IEC should be notified of all 
protocol deviations according to IRB/IEC reporting requirements. Examples deviations included but not 
limited to: 
• 
Failure to obtain informed consent (e.g., there is no documentation of informed consent) for a patient; 
• 
Informed consent is obtained after initiation of study procedures; 
• 
Enrolment of patient who has failed to meet the inclusion/exclusion criteria. 
 
8.3.5 Pharmacokinetics (PK) population 
Not Applicable. 
 
8.4 Demographic and Other Baseline Characteristics 
All demographic and baseline summaries will be based on all the  patients in the Safety analysis Set. 
 
Demographic and baseline characteristics data will be summarized using descriptive statistics (n, mean, 
Standard Deviation, median, minimum, maximum) for continuous variables, and using frequencies and 
percentages for categorical variables by treatment groups and overall. 
 
Demographic characteristics will include age, race, gender, height, etc. 
 
Disease characteristics will include time from initial diagnosis to enrolment, staging, number of prior 
therapies, (systemic therapy, radiotherapy and cancer surgery), type of cancer (locally 
advanced/metastatic), type of metastasis (de novo/recurrent), time from date of last therapy to enrolment, 
ECOG performance status, etc. 
 
The demographic and baseline characteristics will also be summarized by metastasis type (de novo 
metastasis, recurrent (loco regional/distal) metastasis) and overall. 
 
 
8.5 Prior and Concomitant Therapy  
Prior medications are those that are taken only prior to initial dose of study drug. Concomitant medications 
are those that were taken while on study drug. Also, the medications / non-drug treatments which start after 
study treatment end date will be termed as ‘Concomitant’. 
 
The medication data will be coded using WHO-Drug dictionary (WHODRUG GLOBAL B3 March 1, 2021) 
and the non-drug treatments data will be coded using MedDRA dictionary Version 24.0 (Hierarchy). 
 
A summary of frequencies and percentages by ATC level 2 and Preferred Terms  for each treatment group 
along with overall and the listing of the prior and concomitant treatments taken will be provided for all the 
patients in Safety Analysis Set. 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 16 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
 
8.6 Prior Therapies 
Total number of prior systemic therapies in any setting and metastatic setting will be summarized using 
median and range. The prior systemic therapies in metastatic setting will include therapies give after the 
diagnosis of metastatic disease. 
 
Number of prior systemictherapies in any setting and metastatic setting will be summarized using median 
and range.They will also be classified into- 
• 
Chemotherapy 
• 
Aromatase Inhibitors 
• 
Fulvestrant 
• 
CDK4/6 Inhibitors 
• 
Others 
 
 
 
The last prior therapy will be classified in the following categories and will be summarized by frequency and 
percentage- 
• 
    Chemotherapy 
• 
    Aromatase Inhibitors 
• 
    Fulvestrant 
• 
    CDK4/6 Inhibitors 
• 
    Tamoxifen 
 
8.7 Analysis of Efficacy Parameters 
All efficacy parameters will be summarized using ITT and PP analysis set. 
.   
 
In situation, identical patients qualify in ITT and PP analysis set, the statistical summaries for such 
parameters will be presented only for ITT with corresponding note to avoid the replication of results. 
 
 
8.7.1 Analysis of Primary Efficacy Variable 
 
The primary endpoint will be analysed to assess the anti-tumour activity of tenalisib in patients with locally 
advanced or metastatic breast cancer. 
 
The summary of patients without disease progression at the end of 6 months will be provided by frequency 
and percentage along with 95% confidence intervals of these percentages for both the treatment groups. 
The 95% confidence intervals of these percentages will be calculated using exact method based on 
binomial distribution. 
 
The efficacy analysis will also be summarized by metastasis type (de novo metastasis, recurrent 
metastasis) and overall. 
 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 17 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
8.7.2 Analysis of Secondary Efficacy Variables 
These secondary efficacy variables will be analysed and summarised to evaluate safety and tolerability of 
tenalisib. 
 
• 
Overall Response Rate (ORR): It is defined as sum of CR and PR rates. 
The percentages of CR+PR will be calculated and presented along with 95% confidence intervals of these 
percentages.  
This data will be summarized using frequency, and percentage along with 95% confidence intervals of 
these percentages using exact method based on binomial distribution.  
The corresponding listing will also be provided. 
 
• 
Clinical Benefit Rate (CBR): It is defined as sum of CR, PR and SD at 24 weeks or longer. 
The percentages of CR+PR+SD>=24 weeks will be calculated and presented along with 95% confidence 
intervals of these percentages. 
This data will be summarized using frequency, and percentage along with 95% confidence intervals of 
these percentages using exact method based on binomial distribution.  
The corresponding listing will also be provided. 
 
• 
Progression Free Survival (PFS): It is defined as time from the first dose of study drug to 
documented disease progression or death due to any cause.  
PFS is measured from the time of first dose of study drug to radiographic (or tumour marker as 
applicable) documentation of disease progression or death due to any cause. Patients who did not 
progress or die will be censored on the last date the patient is known to be radiologically 
progression free. The summary table for PFS rate at 6-Month and 1-year by metastasis type will 
also be provided. 
 
This variable will be analyzed via Kaplan-Meier methodology and displayed graphically for each treatment 
group and overall. The following reports will be generated: 
• 
The Q1, median and Q3 PFS time will be provided. The 95% CI for the Q1, median, and Q3 PFS time 
will be presented for each treatment group and metastasis group using Brookmeyer-Crowley method. 
• 
The number and % of patients with disease progressive events (further divided into progression or 
death) will be provided. 
• 
The number and % of patients censored (further divided by reasons for censoring) will be provided. 
• 
Kaplan-Meier curves will be produced. 
• 
A listing of PFS data will be provided. 
Additional efficacy variables 
 
Duration of Treatment: Duration of treatment is defined as the time from first dose to last dose of drug. 
 
Duration of response: Duration of response (DoR) is defined as the time from the first occurrence of 
partial or complete response to disease progression or death in patients who achieve complete or partial 
response. For patients who neither progress nor die, the duration of response will be censored on the last 
date the patient is known to be radiologically progression free. This variable will be analyzed via Kaplan-
Meier methodology for each treatment group and overall as well as metastasis type and overall. 
• 
The number and % of patients with partial or complete response. 
• 
The number and % of patients censored (further divided by reasons for censoring) will be provided. 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 18 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
• 
The Q1, median and Q3 will be provided. The 95% CI for the Q1, median, and Q3 will be presented 
using Brookmeyer-Crowley method. 
 
Duration of Clinical benefit: Duration of clinical benefit (DoCB) is defined as the time from the first dose of 
the study drug to disease progression or death in patients who achieve complete response, partial 
response, or stable disease for 24 weeks or longer. For patients who neither progress nor die, the duration 
of response will be censored on the last date the patient is known to be radiologically progression free. This 
variable will be analyzed via Kaplan-Meier methodology for each treatment group and overall as well as 
metastasis type and overall. 
• 
The number and % of patients with partial or complete response or stable disease with 24 weeks or 
longer. 
• 
The number and % of patients censored (further divided by reasons for censoring) will be provided. 
• 
The Q1, median and Q3 will be provided. The 95% CI for the Q1, median, and Q3 will be presented 
using Brookmeyer-Crowley method. 
 
Figures will be provided for best tumor response of each patient in Waterfall plot and visit wise tumor 
response by plotting with change from baseline. 
 
8.7.3 Analysis of Pharmacokinetic Variables  
Not applicable. 
 
8.7.4 Subgroup Analyses 
Here the subgroups to be analysed are as follows: 
 
1. de novo metastasis, recurrent metastasis and Overall      
 
 
8.7.5 Exploratory Analyses 
This is not applicable for this SAP. The same will be prepared by Rhizen and the analysis results 
will be shared for inclusion in the study report. 
 
8.8 Analysis of Safety 
8.8. 1 Duration of Treatment Exposure and Compliance to Study Treatment 
 
• Duration of Treatment  
The duration of treatment (Treatment exposure) to the study medication for patient will be calculated as: 
Treatment Exposure (day) = Last day of dosing – First Day of dosing + 1 
A descriptive summary of duration of treatment (days) will be provided for each treatment group and by 
type of metastasis. In addition, a plot for duration on treatment will be provided per patient. 
 
• Measurements of Treatment Compliance 
For each patient, the treatment compliance is captured for each cycle in the eCRF and is expressed as 
percentage. The treatment compliance, will be summarized descriptively per Cycle for each treatment 
group. This data will be listed for individual patient. 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 19 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
 
8.8.2 Adverse Events 
Adverse events (AEs) will be coded using the Medical Dictionary for Regulatory Activities MedDRA Version 
24.0 (Hierarchy) for the Safety Analysis Set. 
 
The analyses of safety will be based on the frequency of adverse events and their severity for patients in 
each portion who received at least one dose of study treatment. 
Adverse events will be summarised by system organ class and preferred term; a patient will only be 
counted once per system organ class and once per preferred term within a treatment according to the 
maximum NCI CTCAE v.5.0 grade attained. Patient counts and percentages and event counts will be 
presented for each treatment and overall for all the summaries. 
 
Treatment Emergent Adverse Events (TEAEs) are events with start date on or after the date of first dose of 
treatment or events with start date prior to the date of first dose of treatment whose severity worsens on or 
after the date of first dose of treatment. 
 
An overall summary of TEAEs (number and percentage of patients along with the number of events) will be 
presented with the following: 
• 
Any non-TEAE 
• 
Any TEAE 
• 
Related TEAEs 
• 
Serious TEAEs 
• 
Related Serious TEAEs 
• 
Grade >=3 TEAEs 
• 
Related Grade >=3 TEAEs 
• 
TEAEs leading to discontinuation 
• 
Related TEAEs leading to discontinuation 
• 
TEAEs leading to dose reduction 
• 
Related TEAEs leading to dose reduction 
• 
Serious TEAEs leading to discontinuation 
• 
Related Serious TEAEs leading to discontinuation 
• 
TEAEs leading to dose interruptions 
• 
Related TEAEs leading to dose interruptions 
• 
Fatal TEAEs 
• 
Related Fatal TEAEs 
• 
Protocol-Defined Adverse Events of Special Interest: 
▪ 
Pregnancy, abortion, birth defects/congenital anomalies 
▪ 
Overdose 
 
Summaries showing the number of patients (n, %) along with number of events by SOC and PT will be 
provided for the following: 
1. TEAEs 
2. Grade 3, 4 and 5 TEAEs 
3. Treatment-related TEAEs 
4. TEAE with maximum CTCAE grade 
5. Treatment-Emergent SAEs 
6. Treatment-Related SAEs 
7. Treatment-related TEAEs with maximum CTCAE grade 
8. TEAEs leading to dose reduction or interruptions 
9. Treatment-related TEAEs leading to dose reduction or interruptions 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 20 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
10. TEAEs leading to Discontinuation of Study Drug 
11. Treatment-related TEAEs leading to Discontinuation of Study Drug 
12. Deaths 
 
 
No statistical inference between the treatments will be performed on adverse events. 
 
The adverse events data will also be listed for individual patients. 
• 
AEs 
• 
Related TEAEs 
• 
Treatment Emergent Grade 3, 4 and 5 AEs 
• 
Treatment Related Grade 3, 4 and 5 AEs 
• 
Treatment Emergent SAEs 
• 
Treatment Related SAEs 
• 
TEAE leading to discontinuation 
 
8.8.3 Clinical Laboratory Evaluations 
Absolute  and change from baseline values of laboratory parameters(viz. Total bilirubin, Hemoglobin, 
Alkaline phosphatase, Platelet count, ALT, Total WBC, AST, Absolute neutrophil count, GGT, creatinine) 
will be presented using descriptive statistics (n, mean, median, standard deviation, minimum and maximum 
values) for each cycle for each treatment group and overall. 
 
The laboratory data will also be listed. 
A separate listing of patients with abnormal laboratory test values will also be presented. 
Based on the available data which is captured in the database, the laboratory data will be listed for the 
following clinical laboratory parameters: 
 
Hematology 
Chemistry 
Panel I 
Chemistry 
Panel II 
Urinalysis 
Other 
Hematocrit 
Total bilirubin 
Total 
Cholesterol 
Blood 
Serum β-hCG 
Hemoglobin 
Alkaline 
phosphatase 
Triglyceride 
(TG) 
Glucose 
Urine 
pregnancy test 
Platelet count 
ALT 
LDL 
Protein 
PT and INR 
WBC (Total and 
differentials) 
AST 
HDL 
Specific gravity 
 
Serology 
(Hepatitis B, 
Hepatitis C, 
HIV)- Historical 
data is 
acceptable. 
Absolute 
neutrophil count 
LDH 
T3,T4,TSH 
Microscopic 
examb 
 
 
GGT 
 
 
 
 
Blood glucose 
 
 
 
 
Albumin 
 
 
 
 
Total protein 
 
 
 
 
Urea or BUNa 
 
 
 
 
Creatinine 
 
 
 
 
Sodium 
 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 21 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
 
Potassium 
 
 
 
 
Calcium 
 
 
 
 
Phosphorous 
 
 
 
 
Chloride 
 
 
 
a Blood Urea Nitrogen is preferred, if not available Urea may be tested. 
b Microscopic exam, if abnormal results are noted 
 
8.8.4 Other Observations Related to Safety 
 
• 
Vital Signs 
Absolute values of Vital data will be summarized descriptively (n, mean, median, standard deviation, 
minimum and maximum) per cycle for each treatment group and overall. A listing will also be provided. 
 
A separate listing of patients with abnormal vital signs findings will also be presented. 
• 
Physical Findings 
Physical examination data at screening visit and abnormal physical examination data at follow-up visits will 
be listed. 
• 
Electrocardiogram 
Absolute values  of ECG parameters as collected on CRF will be presented through n, mean, median, 
standard deviation, minimum, and maximum per cycle for each treatment group and overall. A summary of 
abnormal ECG results will also be provided per cycle for each treatment group including baseline visit using 
frequencies and percentages. 
A listing of this data will also be provided. Also, a separate listing for the abnormal ECG values will also be 
presented. 
• 
Medical and Surgical history 
This data will be summarized using frequencies and percentages for each treatment group and overall by 
System Organ Class and Preferred Term. A listing will also be provided. 
The medical history data will be coded using MedDRA dictionary Version 24.0 (Hierarchy). 
• 
ECOG 
ECOG performance status as captured in the eCRF will be summarized per cycle with number and 
percentage for each performance status category and treatment group along with overall. This data will 
also be listed. 
• 
Additional listings 
• 
Patient Visits 
• 
Demography 
• 
Main consent and Tumor biopsy informed consent 
• 
Inclusion/Exclusion criteria 
• 
Enrolment status 
• 
Withdrawal or completion of study 
• 
Analysis populations 
• 
Breast Cancer diagnosis 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 22 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
• 
Cancer diagnosis 
• 
Cancer assessment form at screening and follow up visits 
• 
Systemic therapy 
• 
Radiotherapy 
• 
Cancer treatment history surgery 
• 
Study drug exposure 
• 
Study drug accountability 
• 
Target lesion evaluation 
• 
Non-target lesion evaluation 
• 
Overall visit response assessment 
• 
Pregnancy test 
• 
Investigator Comments 
 
 
8.9 Pharmacodynamics 
 
Not Applicable. 
 
 
9. 
Computer Software 
All analyses will be performed by Labcorp Drug Development using Version 9.4 or later of SAS software. 
All summary tables and data listings will be prepared utilising SAS software. 
 
 
10. 
References 
1. Brookmeyer R, Crowley JJ. A confidence interval for the median survival time. Biometrics. 38: 29-
41, 1982. 
 
11. 
Appendices 
 
None. 
 
 
12. 
Table shells and specifications 
 
General programming instructions:  
For tables:  
1. The precision of the summary statistics (mean, median, SD, min, max) and inferential statistics (SE, 
confidence limits) should be as below:  
• 
Mean, median, quartiles, minimum and maximum values, standard deviation (SD), and confidence 
limits (CLs) should be reported with upto 2 decimal places. 
• 
Laboratory data should be reported upto 2 decimal places, as appropriate. 
 
2. All p-values should be reported with precision 0.xxxx. If the p-value is less than 0.0001, the p-value 
should appear in the table as “<0.0001”.  
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 23 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
3. Summary statistics for number of subjects with data summarized/analyzed should be lower case ‘n’ 
or ‘n (%)’. Capital ‘N’ should only be used in column or row headers when indicating the total in the 
denominator, for example (N=xx). 
4. When displaying percentages, if count is 0, no percentage would be displayed.  
 
For Listings: 
1. For listings, if there is no observation in the listing, display the header portion, and display a 
message of “No observation” in the table body text 
 
The following table indicates the necessary outputs to support the report. 
 
Sr. 
No.  
Category  Output 
No.  
Title  
1  
Table  
Table 
14.1.1.1 
Patients Disposition - All Patients 
2  
Table  
Table 
14.1.2.1      
Summary of Protocol Deviations – Safety Analysis Set 
3 
Table  
Table 
14.1.3.1 
Demographic and Baseline Characteristics – Safety Analysis Set 
4 
Table  
Table 
14.1.3.2  
Demographic and Baseline Characteristics for type of metastasis- Safety Analysis Set 
5 
Table  
Table 
14.1.4.1 
Summary of Medical and Surgical History – Safety Analysis Set 
6 
Table  
Table 
14.1.5.1 
Summary of Prior Medications - Safety Analysis Set 
7 
Table  
Table 
14.1.5.2 
Summary of Concomitant Medications - Safety Analysis Set 
8 
Table  
Table 
14.1.5.3 
Summary of Prior Non-Drug Treatments - Safety Analysis Set 
9 
Table  
Table 
14.1.5.4 
Summary of Concomitant Non-Drug Treatments - Safety Analysis Set 
10 
Table  
Table 
14.2.1.1 
Summary of patients without disease progression at the end of 6 months - ITT Analysis Set 
11 
Table  
Table 
14.2.1.2  
Summary of Patients without Disease Progression at the End of 6 Months by Type of 
Metastasis - ITT Analysis Set 
12 
Table  
Table 
14.2.1.3  
Summary of patients without disease progression at the end of 6 months – Per Protocol 
Analysis 
13 
Table  
Table 
14.2.1.3  
Summary of Patients with 6-Month and 1-Year Progression Free Survival – ITT Analysis Set 
14 
Table  
Table 
14.2.1.3  
Summary of Patients with 6-Month and 1-Year Progression Free Survival by Type of 
Metastasis – ITT Analysis Set 
15 
Table  
Table 
14.2.1.3  
Summary of Patients with 6-Month and 1-Year Progression Free Survival – Per Protocol 
Analysis  
16 
Table  
Table 
14.2.2.1 
Summary of Objective Response Rate and Clinical Benefit Rate - ITT Analysis Set 
17 
Table  
Table 
14.2.2.2  
Summary of Objective Response Rate and Clinical Benefit Rate by type of Metastasis- ITT 
Analysis Set 
18 
Table  
Table 
14.2.2.3  
Summary of Objective Response Rate and Clinical Benefit Rate - Per Protocol Analysis 
19 
Table  
Table 
14.2.3.1 
Summary of Progression Free Survival - ITT Analysis Set 
20 
Table  
Table 
14.2.3.2  
Summary of Progression Free Survival by type of metastasis - ITT Analysis Set 
21 
Table  
Table 
14.2.3.3  
Summary of Progression Free Survival - Per Protocol Analysis 
22 
Table  
Table 
14.2.4.1 
Summary of Duration of Response – ITT Analysis Set 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 24 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
23 
Table  
Table 
14.2.4.2  
Summary of Duration of Response by type of metastasis – ITT Analysis Set 
24 
Table  
Table 
14.2.4.3  
Summary of Duration of Response – Per Protocol Analysis 
25 
Table  
Table 
14.2.4.4  
Summary of Duration of clinical benefit – ITT Analysis Set 
26 
Table  
Table 
14.2.4.5  
Summary of Duration of clinical benefit by type of metastasis – ITT Analysis Set 
27 
Table  
Table 
14.2.4.6  
Summary of Duration of clinical benefit – Per Protocol Analysis 
28 
Table  
Table 
14.3.1.1 
Overall Summary of Adverse Events - Safety Analysis Set 
29 
Table  
Table 
14.3.1.2 
Treatment-Emergent Adverse Events by System Organ Class and Preferred Term - Safety 
Analysis Set 
30 
Table  
Table 
14.3.1.3  
Treatment-Emergent Grade 3, 4 and 5 Adverse Events by System Organ Class and Preferred 
Term – Safety Analysis Set 
31 
Table  
Table 
14.3.1.4 
Treatment-Emergent Serious Adverse Events by System Organ Class and Preferred Term - 
Safety Analysis Set 
32 
Table  
Table 
14.3.1.5  
Treatment-Related Serious TEAEs by System Organ Class and Preferred Term - Safety 
Analysis Set 
33 
Table  
Table 
14.3.1.6 
 
Treatment-Emergent Adverse Events by System Organ Class, Preferred Term and maximum 
CTCAE grade - Safety Analysis Set 
34 
Table  
Table 
14.3.1.7  
Treatment-Related TEAEs by System Organ Class, Preferred Term and maximum CTCAE 
grade - Safety Analysis Set 
35 
Table  
Table 
14.3.1.8  
Summary of Deaths by System Organ Class and Preferred Term - Safety Analysis Set 
36 
Table 
Table 
14.3.1.9  
Treatment-Emergent Adverse Events leading to Dose Reduction or Interruptions by System 
Organ Class and Preferred Term – Safety Analysis Set 
37 
Table 
Table 
14.3.1.10  
Treatment-Related TEAEs leading to Dose Reduction or Interruptions by System Organ Class 
and Preferred Term- Safety Analysis Set 
38 
Table 
Table 
14.3.1.11  
Treatment-Emergent Adverse Events leading to Discontinuation of Study Drug by System 
Organ Class and Preferred Term- Safety Analysis Set 
39 
Table 
Table 
14.3.1.12  
Treatment-Related TEAEs leading to Discontinuation of Study Drug by System Organ Class 
and Preferred Term- Safety Analysis Set 
40 
Table  
Table 
14.3.2.1 
Descriptive Summary of Hematology parameters - Safety Analysis Set 
41 
Table  
Table 
14.3.2.2  
Descriptive Summary of Biochemistry parameters - Safety Analysis Set 
42 
Table  
Table 
14.3.3.1  
Descriptive Summary of Vital Signs - Safety Analysis Set 
43 
Table  
Table 
14.3.4.1  
Descriptive Summary of ECG - Safety Analysis Set 
44 
Table  
Table 
14.3.4.2 
Summary of Abnormal ECG results - Safety Analysis Set 
45 
Table  
Table 
14.3.5.1 
Summary of ECOG Performance Status - Safety Analysis Set 
46 
Table  
Table 
14.3.6.1 
Duration of Treatment Exposure and Compliance - Safety Analysis Set 
47 
Table 
Table 
14.3.6.2  
Duration of treatment exposure by type of metastasis – Safety Analysis Set 
48 
Listing  
Listing 
16.2.1.1 
Screened patients - All Patients 
49 
Listing 
Listing 
16.2.1.2 
Randomization - All Enrolled Patients 
50 
Listing 
Listing 
16.2.1.3 
Eligibility Review - All Patients 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 25 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
51 
Listing 
Listing 
16.2.1.4 
Reasons for Withdrawal of Patient from the Study – Safety Analysis Set 
52 
Listing 
Listing 
16.2.1.5 
 
Patient Visits - All Patients 
53 
Listing 
Listing 
16.2.2 
Protocol Deviations during the Study - Safety Analysis Set 
54 
Listing 
Listing 
16.2.3 
Analysis Populations - All Patients 
55 
Listing 
Listing 
16.2.4.1 
Demography Data - Safety Analysis Set 
56 
Listing 
Listing 
16.2.4.2 
Medical History, Surgical History and Concomitant/Current Illnesses - Safety Analysis Set 
57 
Listing 
Listing 
16.2.4.3 
Prior Therapy - Safety Analysis Set 
58 
Listing 
Listing 
16.2.4.4 
Cancer Diagnosis –  Safety Analysis Set 
59 
Listing 
Listing 
16.2.4.5 
Prior and Concomitant Medications - Safety Analysis Set 
60 
Listing  
Listing 
16.2.4.6 
Prior and Concomitant Non-Drug Treatments - Safety Analysis Set 
61 
Listing 
Listing 
16.2.5.1 
Study Drug Exposure - Safety Analysis Set 
62 
Listing 
Listing 
16.2.5.2 
Study Drug Accountability - Safety Analysis Set 
63 
Listing 
Listing 
16.2.6.1 
Cancer Assessment – All Patients  
64 
Listing 
Listing 
16.2.6.2 
Target Lesion Assessment - All Patients 
65 
Listing 
Listing 
16.2.6.3 
Non-Target Lesion assessment - All Patients 
66 
Listing 
Listing 
16.2.6.4 
Overall Tumor assessment - ITT Analysis Set 
67 
Listing 
Listing 
16.2.6.5 
New lesion assessment – ITT Analysis Set 
68 
Listing 
Listing 
16.2.6.6 
Visit Wise Response - ITT Analysis Set 
69 
Listing 
Listing 
16.2.6.7 
ECOG Performance Status - Safety Analysis Set 
70 
Listing 
Listing 
16.2.7.1 
Adverse Events - Safety Analysis Set 
71 
Listing 
Listing 
16.2.7.2  
Treatment-Related TEAEs - Safety Analysis Set 
72 
Listing 
Listing 
16.2.7.3  
Treatment-Emergent Grade 3, 4 and 5 Adverse Events - Safety Analysis Set 
73 
Listing  
Listing 
16.2.7.4  
Treatment-Related Grade 3, 4 and 5 TEAEs - Safety Analysis Set 
74 
Listing 
Listing 
16.2.7.5  
Treatment-Emergent Serious Adverse Events - Safety Analysis Set 
75 
Listing 
Listing 
16.2.7.6  
Treatment-Related Serious TEAEs - Safety Analysis Set 
76 
Listing 
Listing 
16.2.7.7  
Treatment-Emergent Adverse Events leading to Discontinuation of study drug – Safety 
Analysis Set 
77 
Listing 
Listing 
16.2.7.8  
Treatment-Emergent Adverse Events leading to death – Safety Analysis Set 
78 
Listing 
Listing 
16.2.8.1.1 
Clinical Laboratory Evaluations – Hematology - Safety Analysis Set 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 26 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
79 
Listing 
Listing 
16.2.8.1.2 
 
Abnormal Laboratory Values – Hematology - Safety Analysis Set 
80 
Listing 
Listing 
16.2.8.2.1  
Clinical Laboratory Evaluations - Biochemistry - Safety Analysis Set 
81 
Listing 
Listing 
16.2.8.2.2  
Abnormal Laboratory Values – Biochemistry – Safety Analysis Set 
82 
Listing 
sting 
16.2.8.3.1 
Clinical Laboratory Evaluations – Urinalysis - Safety Analysis Set 
83 
Listing 
Listing 
16.2.8.3.2 
 
Abnormal Laboratory Values – Urinalysis - Safety Analysis Set 
84 
Listing 
Listing 
16.2.8.4 
 
Pregnancy Test - Safety Analysis Set 
85 
Listing  
Listing 
16.2.9.1 
Vital Signs - Safety Analysis Set 
86 
Listing 
Listing 
16.2.9.2 
 
Abnormal Clinically Significant Vital Signs Values - Safety Analysis Set 
87 
Listing 
Listing 
16.2.10.1 
 
Physical Examination at Screening - Safety Analysis Set 
88 
Listing 
Listing 
16.2.10.2 
 
Follow up Abnormal Physical Examination Results - Safety Analysis Set 
89 
Listing 
Listing 
16.2.11.1 
12-Lead ECG Results - Safety Analysis Set 
90 
Listing 
Listing 
16.2.11.2 
 
Abnormal ECG Values - Safety Analysis Set 
91 
Listing 
Listing 
16.2.12.1 
Comment Logs – All Patients 
 
92 
Figure 
 
Figure 
Figure 
14.1.6.2 
Figure 
14.1.6.3  
Duration of Treatment plot- Safety Analysis Set 
 
Duration of treatment plot by metastasis type – Safety Analysis Set  
93 
Figure 
Figure 
14.2.3.4 
Kaplan-Meier plot for PFS- ITT Analysis Set 
94 
Figure 
Figure 
14.2.3.5  
Kaplan-Meier plot for PFS- Per Protocol Analysis 
95 
Figure 
Figure 
14.2.2.4 
Best Response (% change from Baseline) in sum of lesion diameters plot - ITT Analysis Set 
96 
Figure 
Figure 
14.2.2.5  
Best Response (% change from Baseline) in sum of lesion diameters plot - Per Protocol 
Analysis 
97 
Figure 
Figure 
14.2.2.6 
Visit Wise Tumor Response Plot - ITT Analysis Set 
98 
Figure 
Figure 
14.2.2.7  
Visit Wise Tumor Response Plot - Per Protocol Analysis 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 27 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Protocol RP6530-2101 
                                                                                                                                                                                                                                       Page xx of yy 
Table 14.1.1.1 
 
Patients Disposition 
 
All Patients 
 
 
Tenalisib 800 mg BID 
Tenalisib 1200 mg BID 
Overall 
Total number of patients Screened 
 
 xx 
Number of patients Enrolled 
 
 xx 
 
 
Number of patients Randomized  
  xx  
 xx  
 xx  
 
 
Number (%) of patients 
 
  Completed Cycle 3 
  xx (xx.x) 
 xx (xx.x) 
 xx (xx.x) 
  Completed Cycle 6 
  xx (xx.x) 
 xx (xx.x) 
 xx (xx.x) 
  Completed Cycle 9 
  xx (xx.x) 
 xx (xx.x) 
 xx (xx.x) 
  Completed Cycle 12 
  xx (xx.x) 
 xx (xx.x) 
 xx (xx.x) 
   Completed Cycle 15  
  xx (xx.x) 
 xx (xx.x) 
 xx (xx.x) 
 
 
Discontinued study [n (%)]# 
  xx (xx.x) 
 xx (xx.x) 
 xx (xx.x%) 
Primary reason for discontinuation* 
 
  Adverse Event [n (%)] 
  xx (xx.x) 
 xx (xx.x) 
 xx (xx.x) 
  Death [n (%)]$ 
 
  Disease progression [n (%)] 
  xx (xx.x) 
 xx (xx.x) 
 xx (xx.x) 
  Investigator's decision [n (%}] 
  xx (xx.x) 
 xx (xx.x) 
 xx (xx.x) 
  Other [n (%)] 
  xx (xx.x) 
 xx (xx.x) 
 xx (xx.x) 
      Xxxxxxxxx 
  xx (xx.x) 
 xx (xx.x) 
 xx (xx.x) 
  Etc. 
 
 
 
Number (%) of patients in 
 
   Safety Analysis Set 
  xx (xx.x) 
 xx (xx.x) 
 xx (xx.x) 
   Intent-To-Treat Analysis Set 
  xx (xx.x) 
 xx (xx.x) 
 xx (xx.x) 
   Per Protocol Analysis Set 
  xx (xx.x) 
 xx (xx.x) 
 xx (xx.x) 
 
 
Number (%) of patients with 
 


 
 
 
 
 
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Protocol RP6530-2101 
                                                                                                                                                                                                                                       Page xx of yy 
Table 14.1.1.1 
 
Patients Disposition 
 
All Patients 
 
 
Tenalisib 800 mg BID 
Tenalisib 1200 mg BID 
Overall 
  Drug interruptions due to AEs 
  xx (xx.x) 
 xx (xx.x) 
 xx (xx.x) 
  Drug discontinuation due to AEs 
  xx (xx.x) 
 xx (xx.x) 
 xx (xx.x) 
  Dose reduction due to AEs ^ 
  xx (xx.x) 
 xx (xx.x) 
 xx (xx.x) 
# Number of patients discontinued at the end of the study. 
*A patient may have multiple reasons for discontinuation from the study and such patients are counted in each reason for discontinuation as reported in the eCRF. 
$A patient who had a non-related adverse event which was documented as "death due to unknown cause" is also recorded an adverse event leading to study discontinuation. 
Percentages are based on the total number of patients randomized in each treatment group. 
Percentages for reason of discontinuation are based on the total number of patients discontinued in each treatment group. 
Safety Analysis Set includes all patients who received at least one dose of study medication. 
Intent-to-Treat Analysis Set includes all patients who received at least one dose of study medication. 
Per Protocol Analysis Set includes all patients in the Intent-to-Treat Set without major protocol deviations. 
Patients under the category 'Drug interruption followed by dose reduction' are counted in both the groups 'Drug interruption' and 'Dose reduction'. 
^The dose reduction information is collated from the treatment exposure page of the eCRF. 
AE:Adverse Event 
Reference Listing xxxxxx 
Program: xx.sas Table Generation: ddmmmyyyy hh:mm:ss 
 
 
 
 


 
 
 
 
 
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Protocol RP6530-2101                                                                                                                                                                                               Page xx of yy 
 
Table 14.1.2.1                                                                                                                                                                                                                                
Summary of Protocol Deviations 
Safety Analysis Set 
 
 
Tenalisib 800 mg BID 
(N=XX) 
n (%), E 
Tenalisib 1200 mg BID 
(N=XX) 
n (%), E 
Overall 
(N=XX) 
n (%), E 
All Protocol Deviations 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Major Protocol Deviations 
Minor Protocol Deviations 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
 
 
 
 
Patients with at least one protocol deviation 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Study medication therapy 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Study Procedure out of time frame/Missing 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Lab Procedure/Assessment missing 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Visit Schedule / Out-of-Window 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Concomitant Medications 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Consent Procedure 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Randomization/Study Drug 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Efficacy Assessment 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Inclusion / Exclusion Criteria 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
 
Percentages are based on the total number of patients (N) in each treatment group. 
n: Number of patients with protocol deviation, E: Number of protocol deviations 
 
Reference Listing xxxxx 
Program: xx.sas Table Generation: ddmmmyyyy hh:mm:ss 
 
 
 


 
 
 
 
 
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Table 14.1.3.1 
 
Demographic and Baseline Characteristics 
 
Safety Analysis Set 
 
Tenalisib 800 mg BID 
(N=XX) 
n (%), E 
Tenalisib 1200 mg BID 
(N=XX) 
n (%), E 
Overall 
(N=XX) 
n (%), E 
Age (years) 
 
 
 
  n 
Xx 
xx 
xx 
  Mean 
xx.xxx 
xx.xxx 
xx.xxx 
  SD 
xx.xxxx 
xx.xxxx 
xx.xxxx 
  Median 
xx.xxx 
xx.xxx 
xx.xxx 
  Min, Max 
xx.xx, xx.xx 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
 
 
 
Race [n (%)] 
 
 
 
  Asian 
xx (xx.xx) 
xx (xx.xx 
xx (xx.xx) 
  Black or African American 
xx (xx.xx) 
xx (xx.xx) 
xx (xx.xx) 
 White/Caucasian 
xx (xx.xx) 
xx (xx.xx) 
xx (xx.xx) 
  Others 
xx (xx.xx) 
xx (xx.xx) 
xx (xx.xx) 
  Unknown/Not reported 
xx (xx.xx) 
xx (xx.xx) 
xx (xx.xx) 
 
 
 
 
Height (cm) 
 
 
 
  n 
Xx 
xx 
xx 
  Mean 
xx.xxx 
xx.xxx 
xx.xxx 
  SD 
xx.xxxx 
xx.xxxx 
xx.xxxx 
  Median 
xx.xxx 
xx.xxx 
xx.xxx 
  Min, Max 
xx.xx, xx.xx 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
 
 
 
Weight (kg) 
 
 
 
  n 
Xx 
xx 
xx 
  Mean 
xx.xxx 
xx.xxx 
xx.xxx 
  SD 
xx.xxxx 
xx.xxxx 
xx.xxxx 
  Median 
xx.xxx 
xx.xxx 
xx.xxx 


 
 
 
 
 
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  Min, Max 
xx.xx, xx.xx 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
 
 
 
Childbearing potential[n (%)] 
 
 
 
  Yes 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  No 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Menopausal status[n (%)] 
 
 
 
  Post-menopausal women 
xx (xx.xx) 
xx (xx.xx) 
xx (xx.xx) 
  Peri-menopausal women 
xx (xx.xx) 
xx (xx.xx) 
xx (xx.xx) 
  Pre-menopausal women 
xx (xx.xx) 
xx (xx.xx) 
xx (xx.xx) 
 


 
 
 
 
 
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Time from the initial diagnosis to enrollment 
(months)* 
 
 
 
   n 
xx 
xx 
Xx 
   Mean 
xx.xxx 
xx.xxx 
xx.xxx 
   SD 
xx.xxxx 
xx.xxxx 
xx.xxxx 
   Median 
   Q1, Q3 
xx.xxx 
xx.xxx, xx.xxx 
xx.xxx 
xx.xxx, xx.xxx 
xx.xxx 
xx.xxx, xx.xxx 
   Min, Max 
xx.xx, xx.xx 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
 
 
 
Number (%) of patients who received  
 
 
 
   Systemic therapies  
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Surgeries 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
   Radiotherapy 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Time from date of last therapy to enrollment (days)* 
 
 
 
   n 
xx 
xx 
xx 
   Mean 
xx.xxx 
xx.xxx 
xx.xxx 
   SD 
xx.xxxx 
xx.xxxx 
xx.xxxx 
   Median 
xx.xxx 
xx.xxx 
xx.xxx 
   Q1, Q3 
xx.xxx, xx.xxx 
xx.xxx, xx.xxx 
xx.xxx, xx.xxx 
   Min, Max 
xx.xx, xx.xx 
xx.xx, xx.xx 
xx.xx, xx.xx 
 
 
 
 
 
 
 
 


 
 
 
 
 
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Total number of prior systemic therapies in any 
setting [Median (Range) ] 
xx (xx-xx) 
xx (xx-xx) 
xx (xx-xx) 
 
 
 
 
Number of patients with prior systemic therapies in 
any setting [n (%)] 
 
 
 
  Therapy < 3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Therapy 3-5 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Therapy > 5 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Total Number of prior systemic therapies in metastatic 
setting [median (range)] 
xx (Range) 
xx (Range) 
xx (Range) 
 
 
 
 
Number of patients with prior systemic therapies in 
metastatic setting [n (%)] 
 
 
 
  Therapy < 3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Therapy 3-5 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Therapy > 5 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  No Therapy 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Number of Patients with prior systemic therapy in any 
Setting , [n (%)] 
 
 
 
    Chemotherapy 
xx (xx-xx) 
xx (xx-xx) 
xx (xx-xx) 
    Aromatase Inhibitors 
xx (xx-xx) 
xx (xx-xx) 
xx (xx-xx) 
    Fulvestrant 
xx (xx-xx) 
xx (xx-xx) 
xx (xx-xx) 
    CDK4/6 Inhibitors 
xx (xx-xx) 
xx (xx-xx) 
xx (xx-xx) 
    Others 
xx (xx-xx) 
xx (xx-xx) 
xx (xx-xx) 
 
 
 
 
Number of Patients with Prior Systemic Therapy in 
Metastatic Setting [n (%)] 
 
 
 
    Chemotherapy 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Aromatase Inhibitors 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Fulvestrant 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    CDK4/6 Inhibitors 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Others 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 


 
 
 
 
 
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Last Prior Therapy [n (%)] 
 
 
 
    Chemotherapy 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Aromatase Inhibitors 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Fulvestrant 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    CDK4/6 Inhibitors 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
    Tamoxifen 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
Stage IVA/IVB [n (%)] 
 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Visceral Disease 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
Non-Visceral Disease 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Metastatic Sites [n (%)] 
 
 
 
         Liver 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
         Lung 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
         Breast 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
         Bone 
xx (xx.x) 
xx (xx.x 
xx (xx.x) 
         Lymph Node 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
No. of lesion sites, n (%) 
    ≥ 3 
 
 
xx (xx.x) 
 
xx (xx.x) 
 
xx (xx.x) 
Subtypes [n (%)] 
 
 
 
ER+ PR+HER- 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
ER+ PR-HER- 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
TNBC 
xx (xx.x%) 
xx (xx.x) 
xx (xx.x%) 
 
 
 
 
ECOG Performance Status** 
 
 
 
  0 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  >=3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 


 
 
 
 
 
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Percentages are based on the total number of patients (N) in each treatment group, Q1: First quartile, Q3: Third Quartile, ECOG:Eastern Cooperative Oncology Group. 
*Partial dates are imputed using the missing data conventions as mentioned in the Statistical analysis plan. 
**The baseline measurement is the last pre-treatment measurement taken on or before Cycle 1 Day 1. 
Q1: First Quartile; Q3: Third Quartile; ECOG: Eastern Cooperative Oncology Group. 
 
Reference Listing 16.2.4.x, 16.2.4.x, etc. 
Program: xx.sas Table Generation: ddmmmyyyy hh:mm:ss 
 
Use same format: 
Table 14.1.3.2 Demographic and Baseline Characteristics for Type of Metastasis- Safety Analysis Set  
<Column 1: same as table 14.1.3.1; Column 2: de novo metastasis; Column 3: recurrent metastasis; Column 4: Overall> 
Add Footnote- “ Recurrent metastasis includes both loco regional and distal metastasis.” 
 
 
 
 


 
 
 
 
 
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Table 14.1.4.1 
Summary of Medical and Surgical History 
Safety Analysis Set 
 
Percentages are based on the total number of patients (N) in each treatment group. 
MedDRA (version 24.0) coding dictionary applied. 
A patient with two or more medical/surgical history terms in the same system organ class (or with the same preferred term) is counted only once for that system organ class (or  
preferred term). 
System organ classes are sorted in alphabetical order. Preferred terms are sorted within system organ class by descending order of frequency of overall preferred terms. 
 
Reference Listing 16.2.4.x 
Program:xx.sas Table Generation:ddmmmyyyy hh:mm:ss 
 
 
 
System Organ Class 
  Preferred Term 
  
Tenalisib 800 mg BID 
(N=XX) 
n (%) 
Tenalisib 1200 mg BID 
(N=XX) 
n (%) 
Overall 
(N=XX) 
n (%) 
Patients with at least one medical/surgical history 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
SOC1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
SOC2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Etc. 
 
 
 


 
 
 
 
 
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Table 14.1.5.1 
Summary of Prior Medications 
Safety Analysis Set 
 
Percentages are based on the total number of patients (N) in each treatment group. 
Medications are coded using WHO-DD classification (version Mar2021). 
A patient with two or more prior medications in the same ATC Level 2 (or with the same preferred term) is counted only once for that ATC Level 2 (or preferred term). 
ATC Level 2 terms are sorted in alphabetical order. Preferred terms are sorted within ATC level 2 terms by descending order of frequency of overall preferred terms. 
Prior medications are those that were taken only prior to the first dose of study drug. 
 
     Reference Listing 16.2.x.x 
Program: xx.sas Table Generation: ddmmmyyyy hh:mm:ss 
 
 
 
ATC Level 2 
  Preferred Term  
  
Tenalisib 800 mg BID 
(N=XX) 
n (%) 
Tenalisib 1200 mg BID 
(N=XX) 
n (%) 
Overall 
(N=XX) 
n (%) 
Patients with at least one Prior Medication 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
ATC1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
ATC2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Etc. 
 
 
 


 
 
 
 
 
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Table 14.1.5.2 
Summary of Concomitant Medications 
Safety Analysis Set 
 
Percentages are based on the total number of patients (N) in each treatment group. 
Medications are coded using WHO-DD classification (version Mar2021). 
A patient with two or more concomitant medications in the same ATC Level 2 (or with the same preferred term) is counted only once for that ATC Level 2 (or preferred term). 
ATC Level 2 terms are sorted in alphabetical order. Preferred terms are sorted within ATC level 2 terms by descending order of frequency of overall preferred terms. 
Concomitant Medication is defined as those taken while on study drug including the ones that started before the initial dose of study drug and the medications which start after 
study drug. 
 
     Reference Listing 16.2.x.x 
Program: xx.sas Table Generation: ddmmmyyyy hh:mm:ss 
 
 
ATC Level 2 
  Preferred Term  
  
Tenalisib 800 mg BID 
(N=XX) 
n (%) 
Tenalisib 1200 mg BID 
(N=XX) 
n (%) 
Overall 
(N=XX) 
n (%) 
Patients with at least one  Concomitant Drug Treatments 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
ATC1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Etc. 
 
 
 


 
 
 
 
 
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Page xx of yy 
Table 14.1.5.3 
Summary of Prior Non-Drug Treatments 
Safety Analysis Set 
Percentages are based on the total number of patients (N) in each treatment group.  
Non-drug treatments are coded using MedDRA (version 24.0). 
A patient with two or more prior non-drug treatments in the same system organ class (or with the same preferred term) is counted only once for that system organ class (or preferred 
term). 
System organ classes are sorted in alphabetical order. Preferred terms are sorted within system organ class by descending order of frequency of overall preferred terms. 
Prior non-drug treatments are those that were taken only prior to the first dose of study drug. 
 
     Reference Listing 16.2.x.x 
Program: xx.sas Table Generation: ddmmmyyyy hh:mm:ss 
 
 
 System Organ Class 
  Preferred Term  
  
Tenalisib 800 mg BID 
(N=XX) 
n (%) 
Tenalisib 1200 mg BID 
(N=XX) 
n (%) 
Overall 
(N=XX) 
n (%) 
Patients with at least one Prior Non-Drug Treatment 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
SOC1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Etc. 
 
 
 


 
 
 
 
 
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Page xx of yy 
Table 14.1.5.4 
Summary of Concomitant Non-Drug Treatments 
Safety Analysis Set 
Percentages are based on the total number of patients (N) in each treatment group.  
A patient with two or more concomitant non-drug treatments in the same system organ class (or with the same preferred term) is counted only once for that system organ class (or 
preferred term). 
Non-drug treatments are coded using MedDRA (version 24.0). 
System organ classes are sorted in alphabetical order. Preferred terms are sorted within system organ class by descending order of frequency of overall preferred terms. 
Concomitant non-drug treatments are those that were taken while on study drug. The non-drug treatments that started after the discontinuation of study drug will also be termed as 
'Concomitant non-drug treatments' 
 
     Reference Listing 16.2.x.x 
Program: xx.sas Table Generation: ddmmmyyyy hh:mm:ss 
 
 
System Organ Class 
  Preferred Term  
  
Tenalisib 800 mg BID 
(N=XX) 
n (%) 
Tenalisib 1200 mg BID 
(N=XX) 
n (%) 
Overall 
(N=XX) 
n (%) 
Patients with at least one Concomitant  
Non-Drug Treatment 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
SOC1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  PT2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Etc. 
 
 
 


 
 
 
 
 
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Table 14.2.1.1 
Summary of Patients Without Disease Progression at the End of 6 Months 
ITT Analysis Set 
 
Tenalisib 800 mg BID  
(N=xx) 
Tenalisib 1200 mg BID 
(N=xx) 
Overall 
(N=xx) 
 
 
 
 
Number (%) of patients without progression at the End of 6 months 
95% CI* 
xx (xx.x) 
(xx.x, xx.x) 
xx (xx.x) 
(xx.x, xx.x) 
xx (xx.x) 
(xx.x, xx.x) 
 
 
 
 
The Intent - to - Treat (ITT) analysis set includes all patients who received at least 1 dose of study medication. 
Percentages are based on the total number of patients (N) in each treatment group. 
* The 95% CIs are reported using exact method based on binomial distribution. 
At 6 months, patients with treatment duration ≥180 days are summarized. 
 
 
Reference Listing 16.2.x.x 
Program: xx.sas Table Generation: ddmmmyyyy hh:mm:ss 
Use same format for 
1. Table 14.2.1.2 Summary of Patients without Disease Progression at the End of 6 Months by Type of Metastasis – ITT Analysis Set 
<Column 1: same as table 14.2.1.1; Column 2: de novo metastasis; Column 3: recurrent metastasis; Column 4: Overall> 
2. Table 14.2.1.3 Summary of Patients without Disease Progression at the End of 6 Months – Per Protocol Analysis  
3. Table 14.2.1.4 Summary of Patients with 6-Month and 1-Year Progression Free Survival – ITT Analysis Set  
<Column 1:  First line “Number (%) of patients without Progressive disease/Death at 6 Month” 
                      Second line “Number (%) of patients without Progressive disease/Death at 1 year;  
Add footnote-“At 1 year, patients with treatment duration ≥360 days are summarized.” 
4. Table 14.2.1.5 Summary of Patients with 6-Month and 1-Year Progression Free Survival by Type of Metastasis – ITT Analysis Set  
<Column 1:  First line “Number (%) of patients without Progressive disease/Death at 6 Month” 
                      Second line “Number (%) of patients without Progressive disease/Death at 1 year;  
Add footnote-“At 1 year, patients with treatment duration ≥360 days are summarized.” 
Column 2: de novo metastasis; Column 3: recurrent metastasis; Column 4: Overall> 
5. Table 14.2.1.6 Summary of Patients with 6-Month and 1-Year Progression Free Survival – Per Protocol Analysis 
 
 
 


 
 
 
 
 
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Protocol RP6530-2101 
Page xx of yy 
Table 14.2.2.1 
Summary of Objective Response Rate and Clinical Benefit Rate  
ITT Analysis Set 
 
 
Tenalisib 800 mg BID  
(N=xx) 
Tenalisib 1200 mg BID 
(N=xx) 
Overall 
(N=xx) 
Number (%) of patients  
95% CI* 
 
 
 
    CR 
xx (xx.x) 
(xx.x, xx.x) 
xx (xx.x) 
(xx.x, xx.x) 
xx (xx.x) 
(xx.x, xx.x) 
 
 
 
 
    PR 
xx (xx.x) 
(xx.x, xx.x) 
xx (xx.x) 
(xx.x, xx.x) 
xx (xx.x) 
(xx.x, xx.x) 
 
 
 
 
    SD 
xx (xx.x) 
(xx.x, xx.x) 
xx (xx.x) 
(xx.x, xx.x) 
xx (xx.x) 
(xx.x, xx.x) 
 
 
 
 
    SD>=24 weeks 
xx (xx.x) 
(xx.x, xx.x) 
xx (xx.x) 
(xx.x, xx.x) 
xx (xx.x) 
(xx.x, xx.x) 
 
 
 
 
    PD 
xx (xx.x) 
(xx.x, xx.x) 
xx (xx.x) 
(xx.x, xx.x) 
xx (xx.x) 
(xx.x, xx.x) 
 
 
 
 
    Not Evaluated 
xx (xx.x) 
(xx.x, xx.x) 
xx (xx.x) 
(xx.x, xx.x) 
xx (xx.x) 
(xx.x, xx.x) 
 
 
 
 
    ORR (CR+PR) 
xx (xx.x) 
(xx.x, xx.x) 
xx (xx.x) 
(xx.x, xx.x) 
xx (xx.x) 
(xx.x, xx.x) 
 
 
 
 
    CBR (CR+PR+SD>=24 weeks) 
xx (xx.x) 
(xx.x, xx.x) 
xx (xx.x) 
(xx.x, xx.x) 
xx (xx.x) 
(xx.x, xx.x) 
The ITT analysis set includes all patients who received at least 1 dose of study medication. 
Percentages are based on the total number of patients (N) in each treatment group. 


 
 
 
 
 
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* The 95% CIs are reported using exact method based on binomial distribution. 
The BOR is defined as the best visit response recorded from the start of the treatment until disease progression/recurrence. The response rates (CR/ PR/ SD/SD>=24 weeks/PD) are 
estimated using (BOR) recorded in each patient. For the patients without any post-baseline efficacy assessment, BOR is considered as 'Not evaluated'. 
For SD ≥24 weeks, patients with treatment duration ≥168 (±7) days are summarized.  
CR- Complete Response; PR- Partial Response; SD- Stable Disease; PD- Progressive Disease; ORR- Objective Response Rate; CBR- Clinical Benefit Rate. 
Reference Listing 16.2.x.x 
Program: xx.sas Table Generation: ddmmmyyyy hh:mm:ss 
Use same format for 
1. Table 14.2.2.2 Summary of Objective Response Rate and Clinical Benefit Rate by type of metastasis – ITT Analysis Set 
<Column 1: same as table 14.2.2.1; Column 2: de novo metastasis; Column 3: recurrent metastasis; Column 4: Overall> 
2. Table 14.2.2.3 Summary of Objective Response Rate and Clinical Benefit Rate – Per Protocol Analysis 
 
 
 


 
 
 
 
 
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Sponsor Protocol ID: RP6530-2101 
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Protocol  RP6530-2101 
Page xx of yy 
Table 14.2.3.1 
Summary of Progression Free Survival  
ITT Analysis Set 
 
 
 
Tenalisib 800 mg BID  
(N=xx) 
Tenalisib 1200 mg BID 
 (N=xx) 
   
Overall 
(N=xx) 
Number (%) of patients with Progressive 
Disease/Death 
xx (xx.x) 
xx (xx.x) 
   
xx (xx.x) 
 
 
 
   
 
       Progressive Disease, n (%) 
xx (xx.x) 
xx (xx.x) 
   
xx (xx.x) 
       Death, n (%) 
xx (xx.x) 
xx (xx.x) 
   
xx (xx.x) 
 
 
 
   
 
Number (%) of censored patients 
xx (xx.x) 
xx (xx.x) 
   
xx (xx.x) 
 
 
 
   
 
Reason for Censoring n(%) 
 
 
   
 
  xxxxxxxxxxxxxxxxx 
xx (xx.x) 
xx (xx.x) 
   
xx (xx.x) 
  xxxxxxxxxxxxxxxxx 
xx (xx.x) 
xx (xx.x) 
   
xx (xx.x) 
 
 
Time to Progressive Disease/ Death (days) 
Quartiles (95% CI)* 
 
 
 
 
  
    Q1 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
 
 
 xx.x (xx.x, xx.x) 
    Median  
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
 
 
 xx.x (xx.x, xx.x) 
    Q3 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
 
 
 xx.x (xx.x, xx.x) 
 
 
 
 
 
  
    Range (min, max) 
(xx,   xx) 
(xx,   xx) 
 
 
 (xx,   xx) 
 
 
 
 
 
The ITT analysis set includes data from all patients who received at least 1 dose of study medication. 
 
Percentages are based on the total number of patients (N) in each treatment group. 


 
 
 
 
 
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Time to Progression Free Survival (PFS) is defined as the time from the first dose of the study drug to documented disease progression or death due to any cause. For 
Patients who neither progress nor die, the duration of response is censored on the last date the patient is known to be radiologically progression free. 
*Quartiles are calculated using Kaplan-Meier Estimate method. The 95% confidence intervals are calculated using Brookmeyer and Crowley Method. 
 
 
 
Reference Listing 16.2.x.x 
Program: xx.sas Table Generation: ddmmmyyyy hh:mm:ss 
 
Use same format for 
1. Table 14.2.3.2 Summary of Progression Free Survival by type of metastasis – ITT Analysis Set 
<Column 1: same as table 14.2.3.1; Column 2: de novo metastasis; Column 3: recurrent metastasis; Column 4: Overall> 
2. Table 14.2.3.3 Summary of Progression Free Survival– Per Protocol Analysis  
 
 
 
 
 
 
 
 
 


 
 
 
 
 
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Protocol RP6530-2101 
Page xx of yy 
Table 14.2.4.1 
Summary of Duration of Response 
ITT Analysis Set 
 
 
Tenalisib 800 mg BID  
(N=xx) 
 
Tenalisib 1200 mg BID 
 (N=xx) 
 
Overall 
(N=xx) 
 
Number (%) of Patients with Partial/Complete 
Response * 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
 
 
 
 
Number (%) of Censored Patients 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
Reason for Censoring n (%) 
 
 
 
         xxxxxxxxxxxxxxxxxxx 
xx.x (xx.x) 
xx.x (xx.x) 
xx.x (xx.x) 
 
 
 
 
Duration of Response (days) 
 
 
 
Quartiles (95% CI)* 
 
 
 
 
         Q1 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
         Median 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
         Q3 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
xx.x (xx.x, xx.x) 
 
 
 
 
Range (min, max) 
(xx,xx) 
(xx,xx) 
(xx,xx) 
 
The ITT is the primary analysis population and will include data from patients who have received at least 1 dose of study medication. 
*Percentages are based on the total number of patients (N) in each treatment group. 
Percentages are based on the total number of patients with Partial/Complete Response in each treatment group. 
 
Duration of Response (DoR) is defined as time from the first occurrence of partial or complete response to disease progression or death in patients who achieve complete 
or partial response. For patients who neither progress nor die, the duration of response is censored on the last date the patient is known to be radiologically progression 
free. 
*Quartiles are calculated using Kaplan-Meier Estimate method. The 95% confidence intervals are displayed using Brookmeyer and Crowley Method.  
 
 
 


 
 
 
 
 
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Program: xx.sas Table Generation: ddmmmyyyy hh:mm:ss  
Use same format for 
1. Table 14.2.4.2 Summary of Duration of Response by type of metastasis – ITT Analysis Set 
<Column 1: same as table 14.2.4.1; Column 2: de novo metastasis; Column 3: recurrent metastasis; Column 4: Overall> 
2. Table 14.2.4.3 Summary of Duration of Response by type of metastasis – Per Protocol Analysis 
 
 
3. Table 14.2.4.4 Summary of Duration of clinical benefit– ITT Analysis Set 
<Column 1: Update the text to “Number (%) of Patients with Partial Response/Complete Response /Stable Disease>=24 weeks”;  
 
 
 
        “Duration of Clinical Benefit (days)” 
Updated footnote as-  
Duration of clinical benefit (DoCB) is defined as the time from the first dose of study drug to disease progression or death in patients who achieve complete response, partial 
response, or stable disease for 24 weeks or longer. For patients who neither progress nor die, the duration of response is censored on the last date the patient is known to be 
radiologically progression free. 
For stable disease ≥24 weeks, patients with treatment duration ≥168 (±7) days are summarized. 
 
4. Table 14.2.4.5 Summary of Duration of clinical benefit by type of metastasis – ITT Analysis Set 
<Column 1: Update the text to “Number (%) of Patients with Partial Response/Complete Response /Stable Disease >= 24 weeks”;  
 
 
 
        “Duration of Clinical Benefit (days)” 
Updated footnote as-  
Duration of clinical benefit (DoCB) is defined as the time from the first dose of study drug to disease progression or death in patients who achieve complete response, partial 
response, or stable disease for 24 weeks or longer. For patients who neither progress nor die, the duration of response is censored on the last date the patient is known to be 
radiologically progression free. 
For stable disease ≥24 weeks, patients with treatment duration ≥168 (±7) days are summarized. 
 
Column 2: de novo metastasis; Column 3: recurrent metastasis; Column 4: Overall> 
5. Table 14.2.4.6 Summary Duration of clinical benefit– Per Protocol Analysis  
<Column 1: Update the text to “Number (%) of Patients with Partial Response/Complete Response /Stable Disease >= 24 weeks”;  
 
 
 
        “Duration of Clinical Benefit (days)” 
Updated footnote as- Duration of clinical benefit (DoCB) is defined as the time from the first dose of study drug to disease progression or death in patients who achieve complete 
response, partial response, or stable disease for 24 weeks or longer. For patients who neither progress nor die, the duration of response is censored on the last date the patient is 
known to be radiologically progression free. For stable disease ≥24 weeks, patients with treatment duration ≥168 (±7) days are summarized 
 
 
 
 


 
 
 
 
 
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Protocol RP6530-2101 
Page xx of yy 
Table 14.3.1.1 
Overall Summary of Adverse Events 
Safety Analysis Set 
 
 
Tenalisib 800 mg BID  
(N=xx) 
n (%), E 
Tenalisib 1200 mg BID 
(N=XX) 
n (%), E 
Overall 
(N=XX) 
n (%), E 
Any non-TEAE 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Any TEAE 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Related TEAEs 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Serious TEAEs 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Related Serious TEAEs 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Grade ≥ 3 TEAEs 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Related Grade ≥ 3 TEAEs 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
TEAEs leading to discontinuation 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Related TEAEs leading to 
discontinuation 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
TEAEs leading to dose reduction^ 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Related TEAEs leading to dose 
reduction^ 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Serious TEAEs leading to 
discontinuation 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Related Serious TEAEs leading to 
discontinuation 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
TEAEs leading to drug interruption 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Related TEAEs leading to 
druginterruption 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Fatal TEAEs 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
Related Fatal TEAEs 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 


 
 
 
 
 
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Sponsor Protocol ID: RP6530-2101 
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Tenalisib 800 mg BID  
(N=xx) 
n (%), E 
Tenalisib 1200 mg BID 
(N=XX) 
n (%), E 
Overall 
(N=XX) 
n (%), E 
Protocol-Defined Adverse Events of 
Special Interest 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
      Pregnancy 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
      Abortion 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
      Birth defects/congenital anomalies 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
      Overdose 
xx (xx.x), xx 
xx (xx.x), xx 
xx (xx.x), xx 
 
 
 
 
 
Percentages are based on the total number of patients (N) in each treatment group. 
 
Treatment-Emergent Adverse Events are those that start on or after the date of first dose of study drug. 
Discontinuation refers to discontinuation of study drug. 
Patients under the category 'Drug interruption followed by dose reduction' are counted in both the groups 'Drug interruption' and 'Dose reduction'. 
^The dose reduction information is collated from the treatment exposure page of the eCRF. 
n: Number of patients with any event, E: Number of events, TEAE: Treatment-Emergent Adverse Event. 
 
Reference Listing 16.2.x.x 
Program: xx.sas Table Generation: ddmmmyyyy hh:mm:ss  
 
 
 
 


 
 
 
 
 
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Sponsor Protocol ID: RP6530-2101 
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Protocol RP6530-2101 
Page xx of yy 
Table 14.3.1.2 
Treatment-Emergent Adverse Events by System Organ Class and Preferred Term 
Safety Analysis Set 
      
System Organ Class 
  Preferred Term  
  
Tenalisib 800 mg BID  
(N=xx) 
Tenalisib 1200 mg BID  
(N=xx) 
 
Overall 
(N=xx) 
 
 
Related  
n (%), E 
Not Related  
n (%), E 
 Total 
n (%), E 
Related  
n (%), E 
Not Related  
n (%), E 
Total 
n (%), E 
Related  
n (%), E 
Not Related  
n (%), E 
Total 
n (%), E 
At Least one TEAE 
x (xx.x), xx 
x (xx.x), xx 
 x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
 
 
 
 
 
 
 
 
 
 
SOC1 
x (xx.x), xx 
x (xx.x), xx 
 x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
  PT1 
x (xx.x), xx 
x (xx.x), xx 
 x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
  PT2 
x (xx.x), xx 
x (xx.x), xx 
 x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
  Etc. 
 
Percentages are based on the total number of patients (N) in each treatment group. 
n: Number of patients with any event, E: Number of events, TEAE: Treatment-Emergent Adverse Event 
A patient with two or more adverse events in the same system organ class (or with the same preferred term) is counted only once for that system organ class (or preferred term). 
Treatment-Emergent Adverse Events are coded using MedDRA (version 24.0) 
A patient experiencing an adverse event at multiple occasions with distinct relationships status with study treatment is counted under both “Related” and “Not Related” categories. The 
events (E) are counted as per their relationship with the study treatment. 
System organ classes are sorted in alphabetical order. Preferred terms are sorted within system organ class by descending order of frequency of overall preferred terms. 
Treatment-Emergent Adverse Events are those that start on or after the date of first dose of study drug. 
Reference Listing 16.2.x.x 
Program: xx.sas Table Generation: ddmmmyyyy hh:mm:ss 
Use same format for 
Table 14.3.1.3 Treatment-Emergent Grade 3, 4 and 5 Adverse Events by System Organ Class and Preferred Term – Safety Analysis Set 
 
 


 
 
 
 
 
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Protocol RP6530-2101                                                                                                                                                                                                                        Page xx of yy 
Table 14.3.1.4 
Treatment-Emergent Serious Adverse Events by System Organ Class and Preferred Term  
Safety Analysis Set 
 
System Organ Class 
  Preferred Term  
  
Tenalisib 800 mg BID  
(N=xx) 
n (%), E 
Tenalisib 1200 mg BID 
(N=xx) 
n (%), E 
Overall 
(N=xx) 
n (%), E 
At Least one TEAE 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
 
 
 
 
SOC1 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
  PT1 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
  PT2 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
  Etc. 
 
 
 
Percentages are based on the total number of patients (N) in each treatment group. 
n: Number of patients with any event, E: Number of events, TEAE: Treatment-Emergent Adverse Event 
A patient with two or more adverse events in the same system organ class (or with the same preferred term) is counted only once for that system organ class (or preferred term). 
Treatment-Emergent Adverse Events are coded using MedDRA (version 24.0) 
System organ classes are sorted in alphabetical order. Preferred terms are sorted within system organ class by descending order of frequency of overall preferred terms. 
Treatment-Emergent Adverse Events are those that start on or after the date of first dose of study drug. 
Reference Listing 16.2.x.x 
Program: xx.sas Table Generation: ddmmmyyyy hh:mm:ss 
 
Use same format for 
Table 14.3.1.5 Treatment-Related Serious TEAEs by System Organ Class and Preferred Term - Safety Analysis Set 
Table 14.3.1.8 Summary of Deaths by System Organ Class and Preferred Term - Safety Analysis Set 
Table 14.3.1.9 Treatment-Emergent Adverse Events leading to Dose Reduction or Interruptions by System Organ Class and Preferred Term – Safety Analysis Set 
Add Footnote –“ Patients under the category 'Drug interruption followed by dose reduction' are counted in both the groups 'Drug interruption' and 'Dose reduction'.” 
                           “^The dose reduction information is collated from the treatment exposure page of the eCRF.” 
Table 14.3.1.10 Treatment-Related TEAEs leading to Dose Reduction or Interruptions by System Organ Class and Preferred Term 
Add Footnote- “Patients under the category 'Drug interruption followed by dose reduction' are counted in both the groups 'Drug interruption' and 'Dose reduction'.” 
                         “^The dose reduction information is collated from the treatment exposure page of the eCRF.” 


 
 
 
 
 
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Table 14.3.1.11 Treatment-Emergent Adverse Events leading to Discontinuation of Study Drug by System Organ Class and Preferred Term 
Table 14.3.1.12 Treatment-Related TEAEs leading to Discontinuation of Study Drug by System Organ Class and Preferred Term 
 
 


 
 
 
 
 
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Sponsor Protocol ID: RP6530-2101 
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Protocol RP6530-1802                                                                                                                                                                                                                             Page xx of yy 
Table 14.3.1.6 
Treatment-Emergent Adverse Events by System Organ Class, Preferred Term and maximum CTCAE grade 
Safety Analysis Set 
 
Percentages are based on the total number of patients (N) in each treatment group.n: Number of patients with any event, E: Number of events, CTCAE: Common Terminology Criteria for 
Adverse Events, TEAE: Treatment-Emergent Adverse Event 
If a patient has two or more adverse events in the same system organ class (or with the same preferred term) with different CTCAE grades, then the event with the highest grade is 
considered for that patient. 
Treatment-Emergent Adverse Events are coded using MedDRA (version 24.0). 
System organ classes are sorted in alphabetical order. Preferred terms are sorted within system organ class by descending order of frequency of overall preferred terms. 
Treatment-Emergent Adverse Events are those that start on or after the date of first dose of study drug. 
CTCAE Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life threatening, 5=Death 
Reference Listing 16.2.7.1 
Program: xx.sas Table Generation: ddmmmyyyy hh:mm:ss 
Use same format for 
System Organ Class 
  Preferred Term 
  
CTCAE 
Grade 
  
Tenalisib 800 mg BID 
(N=xx) 
n (%), E 
Tenalisib 1200 mg BID 
(N=xx) 
n (%), E 
Overall 
(N=xx) 
n (%), E 
At least one TEAE 
Total 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
 
1 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
 
2 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
 
3 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
 
4 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
 
5 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
 
 
 
 
 
Blood and lymphatic system 
disorders 
Total 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
 
1 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
 
2 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
 
3 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
 
4 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
 
5 
x (xx.x), xx 
x (xx.x), xx 
x (xx.x), xx 
Etc 
 
 
 
 


 
 
 
 
 
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Sponsor Protocol ID: RP6530-2101 
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Table 14.3.1.7 Treatment-Related TEAEs by System Organ Class, Preferred Term and maximum CTCAE grade - Safety Analysis Set 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
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Sponsor Protocol ID: RP6530-2101 
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Protocol RP6530-2101 
Page xx of yy 
Table 14.3.2.1 
Descriptive Summary of Hematology parameters 
Safety Analysis Set 
Parmeter (unit): xxxxxxx (xxx) 
 
The baseline measurement is the last pre-treatment measurement taken on or before Cycle 1 Day 1 
Only scheduled visits are included in the table. 
EOT: End of Treatment; NE: Non-Estimable. 
 
Reference Listing 16.2.x.x 
Program: xx.sas Table Generation: ddmmmyyyy hh:mm:ss 
Use same format for 
Table 14.3.2.2 Descriptive Summary of Biochemistry parameters - Safety Analysis Set 
Visit/  
  Statistics 
Tenalisib 800 mg BID 
(N=xx) 
Tenalisib 1200 mg BID 
(N=xx) 
Overall 
(N=xx) 
Actual values 
Change from baseline 
values 
Actual values 
Change from baseline 
values 
Actual values 
Change from baseline 
values 
Baseline 
 
 
 
 
 
 
  N 
   xx 
  xx 
  xx 
  Mean 
   x.xxx 
  x.xxx 
  x.xxx 
  SD 
   x.xxxx 
  x.xxxx 
  x.xxxx 
  Median 
   x.xxx 
  x.xxx 
  x.xxx 
  Min, Max 
   x.xx, x.xx 
  x.xx, x.xx 
  x.xx, x.xx 
 
 
Cycle 1 Day 1 
 
 
 
 
 
 
  N 
   xx 
  xx 
  xx 
  xx 
  xx 
  xx 
  Mean 
   x.xxx 
  x.xxx 
  x.xxx 
  x.xxx 
  x.xxx 
  x.xxx 
  SD 
   x.xxxx 
  x.xxxx 
  x.xxxx 
  x.xxxx 
  x.xxxx 
  x.xxxx 
  Median 
   x.xxx 
  x.xxx 
  x.xxx 
  x.xxx 
  x.xxx 
  x.xxx 
  Min, Max 
   x.xx, x.xx 
  x.xx, x.xx 
  x.xx, x.xx 
  x.xx, x.xx 
  x.xx, x.xx 
  x.xx, x.xx 
 
 
Continue for all visits and parameters 
 
 
 
 
 
 


 
 
 
 
 
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Table 14.3.3.1 Descriptive Summary of Vital Signs - Safety Analysis Set 
 
Note - Please remove the column for change from baseline. 
               Add footnote-“Vitals is collected at Pre-dose during treatment visits” 
Table 14.3.4.1 Descriptive Summary of ECG - Safety Analysis Set 
              Note - Please remove the column for change from baseline. 
               Add footnote-“ECG is collected at Pre-dose during treatment visits” 
 
 
 


 
 
 
 
 
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Table 14.3.4.2 
Summary of Abnormal ECG results 
Safety Analysis Set 
 
Visit  
  
Criteria  
  
Tenalisib 800 mg BID 
(N=xx) 
n (%) 
Tenalisib 1200 mg BID 
(N=xx) 
n (%) 
Overall 
(N=xx) 
n (%) 
Baseline 
Clinically significant 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Not clinically significant 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Cycle 1 Day 15 
Clinically significant 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Not clinically significant 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Cycle 2 Day 1 
Clinically significant 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Not clinically significant 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Cycle 2 Day 15 
Clinically significant 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Not clinically significant 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Cycle 3 Day 1 
Clinically significant 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Not clinically significant 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Cycle 3 Day 15 
Clinically significant 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
Not clinically significant 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Continue for all visits 
 
Percentages are based on the total number of patients (N) in each treatment group. 
The baseline measurement is the last pre-treatment measurement taken on or before Cycle 1 Day 1. 
ECG is collected at Pre-dose during treatment visits 
EOT: End of Treatment. 
 


 
 
 
 
 
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Visit  
  
Criteria  
  
Tenalisib 800 mg BID 
(N=xx) 
n (%) 
Tenalisib 1200 mg BID 
(N=xx) 
n (%) 
Overall 
(N=xx) 
n (%) 
Reference Listing 16.2.x.x 
Program: xx.sas Table Generation: ddmmmyyyy hh:mm:ss 
  
 
 


 
 
 
 
 
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Protocol RP6530-2101 
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Table 14.3.5.1 
Summary of ECOG Performance Status 
Safety Analysis Set 
Visit  
  
  
  
Performance Status 
   
  
Tenalisib 800 mg BID  
(N=xx) 
n (%) 
Tenalisib 1200 mg BID 
(N=xx) 
n (%) 
Overall 
(N=xx) 
n (%) 
Screening 
0 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
3-5 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Cycle 1 Day 1 
0 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
3-5 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Cycle 2 Day 1 
0 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
3-5 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Cycle 3 Day 1 
0 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
1 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
3-5 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Continue for all visits 
 
 
 
 
 
Percentages are based on the total number of patients (N) in each treatment group. 
Only scheduled visits are included in the table. 
Performance Status: 0=Normal activity, 1=Symptoms, but ambulatory, 2=In bed < 50% of the time, 3=In bed > 50% of the time, 4=100% bedridden, 5=Dead 
ECOG: Eastern Cooperative Oncology Group 


 
 
 
 
 
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Reference Listing 16.2.x.x 
Program: xx.sas Table Generation: ddmmmyyyy hh:mm:ss 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
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Protocol RP6530-2101 
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Table 14.3.6.1 
Duration of Treatment Exposure and Compliance 
Safety Analysis Set 
* Duration of treatment exposure = date of last dose - date of first dose + 1. 
** As captured on CRF. 
Q1: first quartile, Q3: third quartile 
 
Reference Listing 16.2.x.x and 16.2x.x 
Program: xx.sas Table Generation: ddmmmyyyy hh:mm:ss 
 
Use same format for 
 
  
Cycle 
Tenalisib 800 mg BID  
(N=xx) 
Tenalisib 1200 mg BID   
(N=xx) 
Overall 
(N=xx) 
 
Duration of Treatment Exposure (days) * Overall 
 
 
 
 
 
   n 
xx 
xx 
xx 
 
 
   Mean 
xx.x 
xx.x 
xx.x 
 
 
   SD 
xx.xx 
xx.xx 
xx.xx 
 
 
   Median 
xx.x 
xx.x 
xx.x 
 
 
   Q1, Q3 
xx.x, xx.x 
xx.x, xx.x 
xx.x, xx.x 
 
 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
Treatment Compliance (%) ** 
Cycle 1 
 
 
 
 
 
   n 
xx 
xx 
xx 
 
 
   Mean 
xx.x 
xx.x 
xx.x 
 
 
   SD 
xx.xx 
xx.xx 
xx.xx 
 
 
   Median 
xx.x 
xx.x 
xx.x 
 
 
   Min, Max 
xx, xx 
xx, xx 
xx, xx 
 
 
 
 
 
 
 
 
Continue for 
remaining 
cycles.. 
 
 
 
 


 
 
 
 
 
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Table 14.3.6.2 Duration of treatment exposure by type of metastasis – Safety Analysis Set 
<Column 1: same as table 14.3.6.1 but treatment compliance part will be removed;  
Column 2: de novo metastasis; Column 3: recurrent metastasis; Column 4: Overall> 
 
 
 


 
 
 
 
 
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Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.1.1 
Screened patients 
All Patients 
 
Patient ID 
Date of Informed 
Consent 
 
Date of Screening 
Is the patient enrolled 
in study? 
If No, please 
comment 
Was Biopsy taken? 
Was Informed 
consent 
Obtained for 
Biopsy 
Testing? 
Date of Informed 
Consent for 
Biopsy/Mutational 
Testing 
xxxx 
DDMMMYYYY 
DDMMMYYYY 
No 
Xxxx 
Yes/ 
Yes 
DDMMMYYYY 
xxxx 
DDMMMYYYY 
DDMMMYYYY 
Yes 
 
Yes 
No 
 
xxxx 
DDMMMYYYY 
DDMMMYYYY 
Yes 
 
No 
 
 
 
 
 
 
 
 
 
 
 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 
 


 
 
 
 
 
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Protocol RP6530-2101 
Listing 16.2.1.2 
Randomization 
All Enrolled Patients 
 
 
 
Patient ID 
Patient Randomized? 
Randomized treatment group 
Xxxx 
Yes                                                    
xxxx 
Xxxx 
Yes                                                    
Xxxx 
 
 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 


 
 
 
 
 
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Protocol RP6530-2101 
Listing 16.2.1.3 
Eligibility Review 
All Patients 
 
 
 
Patient ID 
Is the patient eligible                       Enrollment Status 
for the study? 
If no, Give the Primary reason 
Xxxx 
Yes                                                    No 
xxxx 
Xxxx 
Yes                                                    No 
Xxxx 
 
 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 


 
 
 
 
 
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Page xx of yy 
Listing 16.2.1.4 
Reasons for Withdrawal of Patient from the Study 
Safety Analysis Set 
 
Patient 
ID 
     
Treatment 
Group 
Date of 
First/Last dose of 
Tenalisib 
administered 
Last dose  
administered 
Date of 
discontinuation/ 
Study Day 
Primary reason 
for discontinuation 
In case of AE, 
Specify 
AE No# 
In case of 
Progression 
(Date of 
progression) 
In case of 
Death 
(Date of 
death) 
Was death 
caused by the  
toxicity of 
study drug 
 
Primary cause 
of death 
Xxxx 
Xxxx 
DDMMMYYYY/D
DMMMYYYY 
xxxx 
DDMMMYYYY/x
x 
xxxx 
xx 
 
 
 
Xxxx 
Xxxx 
DDMMMYYYY/D
DMMMYYYY 
xxxx 
DDMMMYYYY/x
x 
xxxx 
 
DDMMMYYYY 
DDMMMYY
YY 
No 
Study Day = Treatment start date – Date of discontinuation +1 
#: Related to study drug 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 


 
 
 
 
 
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Protocol RP6530-2101                                                                                                                                      
                                                              Page xx of yy 
Listing 16.2.1.5 
Patient Visits 
All Patients 
Patient ID 
Treatment Group 
Visit                  Date of Visit  
                                                 
Was this Visit Performed 
Reason for visit not performed  
Adverse event from 
previous visit? 
Concomitant 
medication from previous 
visit? 
Xxxx 
Xxxxxx 
xxxx                  DDMMMYYYY 
Yes 
Yes 
No 
 
Xxxxxx 
xxxx 
No 
xxxxxxxxxxxxxx 
 
xxxx 
 
 
 
 
 
 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 


 
 
 
 
 
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Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.2 
Protocol Deviations during the Study 
Safety Analysis Set 
 
 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 
Patient 
ID 
Treatment Group 
Date of  Deviation                           Type of Protocol Deviation (Main 
Category) 
Description of Protocol 
Deviation 
(SubCategory) 
Category 
Requires Exclusion from 
PP Set 
Xxxx 
Xxxx 
 DDMMMYYYY 
xxxxxxxxxxx 
Xxxxxxxxxxx 
Minor 
No 
 
 DDMMMYYYY 
xxxxxxxxxxx 
Xxxxxxxxxxx 
Major 
Yes 
 
 
Xxxx 
Xxxxx 
  DDMMMYYYY 
xxxxxxxxxxx 
Xxxxxxxxxxx 
Minor 
 


 
 
 
 
 
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Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.3 
Analysis Populations 
All Patients 
 
 
Patient 
ID 
 
Treatment Group Safety Analysis 
Set 
Intent-to-Treat Analysis 
Set  
Per Protocol Analysis Set  
Reason for exclusion from Intent-to-
Treat Analysis Set 
Reason for exclusion from Per 
Protocol Analysis Set 
Xxxx 
 
Xxxxx 
Yes 
Yes 
Yes 
 
Xxxx 
 
Xxxxx 
Yes 
No 
No 
 
xxxxx 
 
 
 
 
 
 
 
 
Safety Analysis Set includes all patients who received at least one dose of study medication. 
Intent-to-Treat Analysis Set includes all patients who received at least one dose of study medication. 
Per Protocol Analysis Set includes all patients in the Intent-to-Treat Analysis Set without major protocol deviations. 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 


 
 
 
 
 
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Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.4.1 
Demography Data 
Safety Analysis Set 
 
 
 
 
 
Patient 
ID 
Treatment Group 
Type of metastasis 
Date of Birth 
Age (years) Gender 
Race 
Height 
(cm) 
 
Childbearing potential? 
Menopausal status 
Xxxx 
Xxxxx 
de novo metastasis 
DDMMMYYYY 
xx.xx 
Female 
Xxxx 
xx.xx 
 
Post-menopausal 
Xxxx 
Xxxxx 
Recurrent metastasis DDMMMYYYY 
xx.xx 
Female 
Other:Xxxx 
xx.xx 
No 
 
 
 
 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
  
 
 


 
 
 
 
 
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Listing 16.2.4.2 
Medical History, Surgical History and Concomitant/Current Illnesses 
Safety Analysis Set 
 
 
Patient 
ID 
Treatment Group Event 
Code 
MH Verbatim Term SOC /Preferred Term 
Start Date 
End Date/ 
Ongoing 
Any Medication 
Ongoing 
If prior medication specify 
number 
Xxxx 
Xxxxx 
1 
xxxx 
xxxx / xxxx 
DDMMMYYYY 
Ongoing 
Yes 
 
2 
xxxx 
xxxx / xxxx 
DDMMMYYYY 
DDMMMYYYY 
No 
 
3 
xxxx 
xxxx / xxxx 
DDMMMYYYY 
Ongoing 
Yes 
 
4 
xxxx 
xxxx / xxxx 
DDMMMYYYY 
Ongoing 
No 
 
5 
xxxx 
xxxx / xxxx 
DDMMMYYYY 
DDMMMYYYY 
No 
 
6 
xxxx 
xxxx / xxxx 
DDMMMYYYY 
DDMMMYYYY 
Yes 
 
MH: Medical history, SOC: System organ class 
MedDRA (version 24.0) coding dictionary applied. 
 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
  
 


 
 
 
 
 
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Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.4.3 
Prior Therapy 
Safety Analysis Set 
 
 
 
 
 
 
 
Patient 
ID 
Treatment 
Group 
Total Therapies 
undergone 
prior to start of 
study 
Type of 
therapy 
Number of 
Systemic 
Therapies/ 
Radiotherapies/
Surgeries 
Prior to Start 
of Study 
Systemic 
Therapy/ SCT/ 
Type of 
Radiotherapy 
Start Date / 
End Date 
or 
Date of 
Surgery 
 
No. of cycles/ 
Total 
Radiation 
Dose 
Site of Surgery/ 
Radiotherapy 
 
Radio therapy given 
along with 
chemotherapy? 
 
Treatment 
Status/Best 
Response * 
Xxxx Xxxxx 
xx 
Systemic 
Therapy 
xxxx 
DDMMM
YYYY / 
DDMMM
YYYY 
           xx 
xxx 
 
 
Xx/xxx 
 
 
Radiotherapy 
xxxxxxxxx 
DDMMM
YYYY / 
DDMMM
YYYY 
            
xxxx 
 
Yes 
 
Xx/xxx 
 
 
Surgery 
Other: xxxx 
DDMMM
YYYY  
 
            
xxxx 
 
 
Xx/xxxx 
 
 
 
 
 
 
 
 
 
 
 
*Best Response: SD: Stable Disease; CR: Complete Response; PR: Partial Response; PD: Progressive Disease; ND: Not Assessed/Done; NE: Not Evaluable; UN: Unknown; NA: Not 
Applicable. 
#Last systemic therapy prior to start of study. 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
  
 


 
 
 
 
 
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Protocol RP6530-2101                                                                                                                                                                                                                 Page xx of yy 
Listing 16.2.4.4                                                                                                                                                                                                                             
Cancer Diagnosis 
Safety Analysis Set 
Patient 
ID 
Treatment Group Date of Primary 
Diagnosis  
 
 
Metastatic/ Locally 
Advanced 
Metastasis at the 
time of primary 
presentation 
If No, Date of 
diagnosis of 
metastatic disease 
Type of 
metastasis 
TNM 
Staging 
Histology 
Hormone receptor 
status 
Xxxx 
Xxxxx 
DDMMMYYYY 
 
Metastatic 
Yes 
DDMMMYYYY 
xxxxxxxxx 
IA1 
xxxxxxxxx 
xxxxxxxxx 
 
 
 
Xxxx 
Xxxxx 
DDMMMYYYY 
 
Metastatic 
Yes 
DDMMMYYYY 
xxxxxxxxx 
IA1 
xxxxxxxxx 
xxxxxxxxx 
 
 
 
Xxxx 
Xxxxx 
DDMMMYYYY 
 
Metastatic 
Yes 
DDMMMYYYY 
xxxxxxxxx 
IA1 
xxxxxxxxx 
xxxxxxxxx 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 


 
 
 
 
 
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Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.4.5 
Prior and Concomitant Medications 
Safety Analysis Set 
 
 
Patient 
ID 
 
Treatment Group 
ATC Level 2/ 
Preferred Term/ 
Medication Name 
Reason for 
therapy 
 
Start Date 
 
Stop Date/ 
Ongoing 
Dose/Unit 
  
 
Frequency/Route 
  
 
Prior 
or 
Concomitant 
Xxxx Xxxxxx 
xxxx/ 
xxxx/ 
xxxx 
MH: xxxx 
DDMMMYYYY 
Ongoing 
Xx/xxx 
 
Xxxx/xxxx 
 
C 
 
 
 
 
 
 
 
 
 
 
 
xxxx/ 
xxxx/ 
xxxx 
AE: xxxx 
DDMMMYYYY 
Ongoing 
Xx/xxx 
 
Xxxx/xxxx 
 
C 
 
 
 
 
 
 
 
 
 
 
 
xxxx/ 
xxxx/ 
xxxx 
Other: xxxx 
DDMMMYYYY 
DDMMMYYYY Xx/xxx 
 
Xxxx/xxxx 
 
P 
MH: Medical History; AE: Adverse Event; P: Prior; C=Concomitant. 
Medications are coded using WHO-DD classification (version Mar2021) 
Prior medications are those that were taken only prior to the first dose of study drug.  
Concomitant Medication is defined as those taken while on study drug including the ones that started before the initial dose of study drug and the medications which start after study drug. 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 


 
 
 
 
 
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Sponsor Protocol ID: RP6530-2101 
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Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.4.6 
Prior and Concomitant Non-Drug Treatments 
Safety Analysis Set 
 Patient 
 ID 
 
Treatment Group 
System Organ Class/ 
Preferred Term/ 
Treatment Name 
Reason for 
therapy 
 
Start Date 
 
Stop Date/ 
Ongoing 
 Any 
Comment 
Prior or 
Concomitant 
Treatment 
 Xxxx 
Xxxxxxx 
xxxx/ 
xxxx/ 
xxxx 
AE: xxxx 
DDMMMYYYY 
DDMMMYYYY 
xxxx 
C 
 
 
 
 
 
 
 
 
 
xxxx/ 
xxxx/ 
xxxx 
Other:xxxx 
DDMMMYYYY 
Ongoing 
xxxx 
C 
 
 
 
 
 
 
 
 
 
xxxx/ 
xxxx/ 
xxxx 
MH:xxxx 
DDMMMYYYY 
DDMMMYYYY 
xxxx 
P 
 
 
 
MH: Medical History; AE: Adverse Event; P: Prior; C=Concomitant. 
Non drug treatments are coded using MedDRA (version 24.0) 
Prior non-drug treatments are those that were taken only prior to the first dose of study drug.  
Concomitant non-drug treatments are those that were taken while on study drug. The non-drug treatments that started after the discontinuation of study drug will also be termed as 
'Concomitant non-drug treatments'. 
 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 


 
 
 
 
 
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CONFIDENTIAL 
Page 76 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.5.1 
Study Drug Exposure 
Safety Analysis Set 
 
 
 
Patient 
ID 
 
Treatment Group Type of 
metastasis 
Cycle 
  
Start date/ 
Stop date 
Dose prescribed 
(mg)/ 
Dose administered 
(mg) 
 
Action taken to 
study drug 
  
Reason for action taken 
  
Xxxx 
 Xxxxxxx 
xxxxxxxx 
Cycle 1  
DDMMMYYYY/ 
DDMMMYYYY 
800 mg /800 mg 
 
xxx 
Adverse event/toxicity: AE# 5 
 
 
 
 
 
 
 
 
 
 
 
DDMMMYYYY/ 
DDMMMYYYY 
800 mg /800mg 
 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
EOT 
DDMMMYYYY/ 
DDMMMYYYY 
800 mg /800mg 
 
xxx 
Other: xxx 
 
EOT: End of Treatment 
 
 
 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 77 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Protocol RP6530-2101                                                                                                                                                                                                                       Page xx of yy 
Listing 16.2.5.2 
Study Drug Accountability 
Safety Analysis Set 
Patient 
ID 
   
Treatment 
Group 
Dispensed Cycle/ 
Return Cycle 
Date dispensed/ 
Returned 
Strength  
of tablet 
  
  
Dose  
prescribe 
per day 
(mg) 
 
 No. of 
tablets  
Dispensed/ 
Returned 
  
No. of 
days 
drug 
interruptio
n 
 
Dose reduction 
between 
cycle/Date of 
dose reduction 
Dose of the 
study drug 
after dose 
reduction 
No. of days 
drug 
interruption 
after dose 
reduction 
Compliance 
(%) 
 
 
Comments 
  
  
  
xxxx Xxxxx 
  xxxx/xxxx 
DDMMMYYYY/ 
DDMMMYYYY 
xxx 
xxx 
xxxx 
xx  
 No 
xx 
 
xx 
xxxx 
xxxx Xxxx 
  xxxx/xxxx 
DDMMMYYYY / 
DDMMMYYYY 
xxx 
xxx 
xxxx 
xx  
 Yes/ 
DDMMMYYY
Y 
xx 
 
xx 
 
 
 
 
EOT: End of Treatment 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 78 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.6.1 
Cancer Assessment 
All Patients 
 
 
 
 
EOT: End of Treatment 
 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 
Patient 
ID 
Treatment 
Group 
Type of 
Metastasis 
ITT/PP 
 Visit 
 Assessment 
performed/Date of 
Assessment 
 Reason if 
assessment 
not 
performed 
Lesion site  
Presence of 
lesion 
 
 
Number/Location 
of Lesion within 
site 
 
Site name/ 
Number of 
Lesion 
within 
other site or 
soft tissue) 
xxxx 
Xxxxxx 
xxxxxx 
Yes/Yes 
Screening 
Yes/DDMMMYYYY  xxxxxx 
Breast 
Lymph 
nodes 
Lung 
Yes 
No 
No 
1 
 
 
 
 
 
 
 
 
 
Liver 
 
 
 
 
 
 
 
 
 
 
 
Bone 
Other soft 
tissue 
 
 
 
 
 
Repeat for all the sites 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 79 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.6.2 
Target Lesion Assessment 
All Patients 
 
Patient 
ID 
Treatment 
Group 
 
Type of 
metastasis 
 ITT/PP 
Number of 
Measurable 
Lesions/ 
Target Lesions 
at Screening 
Visit 
Assessment Performed/ 
Date of Assessment 
Evaluation 
Method  
 Lesion 
Number/ 
Anatomical 
Location 
 Tumor 
Laterality/ 
Lesion 
Diameter 
(cm) 
 Sum 
of lesion 
diameters 
% Change 
from Nadir/ 
% Change 
in SLD from 
Baseline# 
>0.5cm 
Absolute 
Increase in 
Any Lesion 
Size/ 
Overall 
Response 
of Target 
Lesions 
Xxxx Xxxxxx xxxxxxxx  Yes/Yes 
x/x 
Screening 
Yes/DDMMMYYYY 
CT 
1/xxxxxx 
Left/xx.x  xx.x 
xx.x/xx.x 
Xx/xx 
 
 
 
 
 
 
 
 
CT 
1/xxxxxx 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Yes/Yes 
xx/xx 
Cycle 3 Day1 
 Yes/DDMMMYYYY 
CT 
1/xxxxxx 
 Left/xx.x   xx.x 
xx.x/xx.xx 
Xx/xx 
 
ITT: Intent-To-Treat Analysis Set, PP: Per Protocol Analysis Set, EOT: End of Treatment,SLD: Sum of Lesion Diameter 
#((SLD at Visit – SLD at Screening)/SLD at Screening)x100 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
  
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 80 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.6.3 
Non-Target Lesion Assessment 
All Patients 
 
 
 
 
ITT: Intent-To-Treat Analysis Set, PP: Per Protocol Analysis Set, EOT: End of Treatment 
 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 
 
Patient 
ID 
Treatment 
Group 
Type of 
metastasis 
ITT/PP 
Non-
target 
Lesion at 
screening 
Visit     
Was Assessment 
Performed? 
Date of 
Assessment     
Non-target 
Lesion 
Complete 
Resolved? 
Evaluation 
Method  
Lesion 
Number/ 
Anatomical 
Location  
Tumor 
Laterality 
 Lesion 
Present 
at 
Screening 
Any 
unequivocal 
increase in 
lesion 
Overall 
Response 
of Non-
Target 
Lesions 
xxxx 
Xxxxx 
xxxxxx 
Yes/Yes 
Yes 
Screening 
Yes/ 
DDMMMYYYY 
No 
CT 
1/xxxx 
Right 
No 
No 
xxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxx 
Xxxxx 
xxxxx 
Yes/Yes 
Yes 
Cycle 3 
Day 1 
 
Yes/ 
DDMMMYYYY 
No 
CT 
1/xxxx 
Left 
 No 
No 
xxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 81 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
 
 
Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.6.4 
Overall Tumor assessment 
ITT Analysis Set 
 
 
 
 
 Patient 
ID 
Treatment 
Group 
Type of 
metastasis  PP 
Visit 
Overall 
tumor 
assessment 
performed? 
If No, reason 
Overall 
assessment 
date 
Overall 
Response 
If progressive disease, date of 
first radiological evidence of 
progression 
 
 
 xxxx 
Xxxx 
Xxxxx 
 Yes 
xxxx 
Yes 
DDMMMYYYY 
Xxxxx 
DDMMMYYYY 
 
  
 
 
 
 
 
 
 
 
 
 
 
 xxxx 
Xxxxx 
xxxxx 
 Yes 
xxxx 
Yes 
 
DDMMMYYYY 
xxxxx 
 
 
 
 
 xxxx 
Xxxxx 
xxxxx 
 
xxxx 
Yes 
DDMMMYYYY 
xxxxx 
 
 
 xxxx 
Xxxxx 
xxxxx 
 
xxxx 
No 
xxx 
 
 
 
 
 
 
 
 
ITT: Intent-To-Treat Analysis Set, PP: Per Protocol Analysis Set, EOT: End of Treatment 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 82 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.6.5 
New lesion assessment 
ITT Analysis Set 
 
 
 
 
 
 Patient 
ID 
Treatment 
Group 
 
Type of 
metastasis 
 PP 
Visit 
Any New Lesion? 
 
Date of Detecting 
New Lesion 
Number of 
new lesions 
New lesion 
site 
Method of 
assessment 
Dimension, 
If 
Applicable 
(cm) 
 
 Xxxx 
Xxxx 
xxxx 
 Yes 
xxxx 
Yes 
DDMMMYYYY 
Xx 
xxx 
Xxxx 
xx 
 
  
 
 
 
 
 
 
 
 
 
 
 
 Xxxx 
Xxxxx 
xxxxx 
 Yes 
xxxx 
Yes 
DDMMMYYYY 
Xx 
xxx 
Xxxx 
xx 
 
 
 Xxxx 
Xxxxxx 
xxxxxx 
 Yes 
xxxx 
Yes 
DDMMMYYYY 
Xx 
xxxx 
Xxxx 
 
 
 
 Xxxx 
Xxxxx 
xxxxxx 
 Yes 
xxxx 
No 
 
 
 
 
 
 Xxxx 
Xxxxx 
xxxxxx 
 Yes 
xxxx 
Yes 
DDMMMYYYY 
xx 
xxx 
Xxxx 
 
  
 
 
 
 
 
 
 
 
 
 
 
 Xxxx 
Xxxxx 
xxxxxx 
 Yes 
xxxx 
No 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ITT: Intent-To-Treat Analysis Set, PP: Per Protocol Analysis Set, EOT: End of Treatment 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 
 
 
Protocol RP6530-1802 
Page xx of yy 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 83 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Listing 16.2.6.6 
Visit Wise Response 
ITT Analysis Set 
 
 
 
 
 
 
 
 
 
 
Patient 
ID 
Treatment 
Group 
Type of 
Metastasis 
PP 
C3D1 C5D1 C7D1 C9D1 C11D1 C13D1 C15D1 C17D1 C19D1 
EOT 
BOR 
 DOT(in 
Days) 
DOR (in 
Days)  
Best Change from 
baseline 
xxxx 
Xxxx 
Xxxxxxxx 
Yes 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
Xx 
Xx 
Xxxxx 
xxxx 
Xxxx 
Xxxxxxx 
Yes 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
Xx 
Xx 
Xxxxx 
xxxx 
Xxxx 
Xxxxxxxx 
Yes 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
Xx 
Xx 
Xxxxx 
xxxx 
Xxxx 
Xxxxxxx 
Yes 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
Xx 
Xx 
Xxxxxx 
xxxx 
Xxxx 
Xxxxxxx 
Yes 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
Xxxxxx 
xxxx 
Xxxx 
xxxxxxxxx Yes 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xx 
xxxxxx 
 
 
 
 
 
 
 
 
 
 
 
The BOR is defined as the best visit response recorded from the start of the treatment until disease progression/recurrence. For the patients without any post-baseline efficacy assessment, 
BOR is considered as 'Not evaluated'. 
Duration of Treatment (DOT) = Date of Last Dose - Date of First Dose + 1. 
Duration of Response (DOR) is defined as time from the first occurrence of partial or complete response to disease progression or death in patients who achieve complete or partial 
response. For patients who neither progress nor die, the duration of response is censored on the last date the patient is known to be radiologically progression free. 
Best change from baseline represents the smallest value of change from baseline in sum of lesion diameter among all the visits. 
CR: Complete Response; PR: Partial Response; SD: Stable Disease; PD: Progressive Disease. 
EOT: End of Treatment; BOR: Best Overall Response; DOT: Duration of Treatment; DOR: Duration of Response; NA: Not Applicable; NE: Not Evaluated; 
ITT: Intent-to-Treat Analysis Set; PP: Per-Protocol Analysis Set. 
 
 
 
 
 
 
 
 
 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 84 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
 
Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.6.7 
ECOG Performance Status 
Safety Analysis Set 
 
 
 
Patient 
ID 
Treatment Group 
Visit 
 
Date of 
Assessment 
Performance 
Status 
Reason assessment not performed 
Xxxx 
Xxxxxx 
Screening 
DDMMMYYYY 
1 
 
 
Cycle 1 Day 1 
DDMMMYYYY 
1 
 
 
Cycle 2 Day 1 
Ect 
DDMMMYYYY 
1  
 
 
End Of Treatment 
DDMMMYYYY 
1 
 
 
 
 
 
 
xxxx  
Xxxxxx 
Screening 
DDMMMYYYY 
1 
 
 
Cycle 1 Day 1 
DDMMMYYYY 
0 
 
 
Cycle 2 Day 1 
Ect 
DDMMMYYYY 
1  
 
 
End Of Treatment 
 
 
xxxx 
 
 
 
Performance Status: 0=Normal activity, 1=Symptoms, but ambulatory, 2=In bed < 50% of the time, 3=In bed > 50% of the time, 4=100% bedridden, 5=Dead 
ECOG: Eastern Cooperative Oncology Group; EOT:End of Treatment. 
 
 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 85 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.7.1 
Adverse Events 
Safety Analysis Set 
 
 
Patient 
ID 
Treatment Group 
Event Code / 
SOC / 
Preferred 
Term / 
AE Verbatim Term* 
Onset Date [Study Day] / 
End Date [Study Day] / 
AE Duration (days) 
CTCAE/ 
SAE 
SAE Criteria  
Action Taken with Study 
Drug / 
Relationship to Study Drug / 
Outcome 
Treatment 
Given 
for AE 
Xxxx 
Xxxxxx 
xx/  
xxxx/ 
xxxx/ 
xxxx 
DDMMMYYYY [xx]/ 
DDMMMYYYY [xx]/ 
xx  
 
Gradexx/ 
No 
No 
xxxxxxxx 
xxxx/ 
xxxxx/ 
xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
SOC: System Organ Class, CTCAE: Common Terminology Criteria for Adverse Events 
Adverse events are coded using MedDRA version 24.0 
CTCAE Grade: 1=Mild, 2=Moderate, 3=Severe, 4=Life threatening, 5=Death 
Study Day = (Onset date/End date) -Treatment start date + 1 
*: Non-treatment-emergent adverse events 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 86 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Use same format for 
 
<Note to Programmer: Please add the footnote “Treatment-Emergent Adverse Events are those that start on or after the date of first dose of study drug.”> 
 
Listing 16.2.7.2 Treatment-Related TEAEs - Safety Analysis Set  
Listing 16.2.7.3 Treatment-Emergent Grade 3, 4 and 5 Adverse Events - Safety Analysis Set 
Listing 16.2.7.4 Treatment-Related Grade 3, 4 and 5 TEAEs - Safety Analysis Set 
Listing 16.2.7.5 Treatment-Emergent Serious Adverse Events - Safety Analysis Set 
Listing 16.2.7.6 Treatment-Related Serious TEAEs - Safety Analysis Set 
Listing 16.2.7.7 Treatment-Emergent Adverse Events leading to Discontinuation of study drug - Safety Analysis Set  
Listing 16.2.7.8 Treatment-Emergent Adverse Events leading to death - Safety Analysis Set  
 
 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 87 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
 
Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.8.1.1 
Clinical Laboratory Evaluations – Hematology 
Safety Analysis Set 
 
 
 
 
Patient 
ID 
Treatment Group 
Visit 
Date/Time of 
Collection 
Test Name 
 
Result 
 
Unit 
 
LLN 
ULN 
Normal/Abnormal 
 
In case of CS, Specify 
AE No 
Xxxx 
Xxxxxx 
Screening 
DDMMMYYYY/ 
hh:mm 
Xxxx 
xx.x 
xx 
xx.x 
xx.x 
Normal 
 
 
 
Xxxx 
xx.x 
xx 
xx 
xx 
Abnormal, NCS 
 
NCS: Not Clinically Significant; CS: Clinically Significant; EOT: End of Treatment; Clinical significance is applicable if results are out of reference range; LLN: Lower Limit of 
Normal; ULN: Upper Limit of Normal 
 
 
 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
Use same format for 
Listing 16.2.8.2.1 Clinical Laboratory Evaluations - Biochemistry - Safety Analysis Set 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 88 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Protocol RP6530-2101 
 
Page xx of yy 
Listing 16.2.8.1.2 
Abnormal Laboratory Values – Hematology 
Safety Analysis Set 
 
 
 
Patient 
ID 
Treatment 
Group 
Visit 
 
Date/Time of 
Collection 
Test Name 
 
Result 
 
Unit 
 
LLN 
ULN 
Clinically 
Significant? 
In case of CS, 
Specify 
AE No 
Xxxx Xxxxx 
Screening 
DDMMMYYYY/hh:mm 
Xxxx 
xx.x 
xx 
xx.x 
xx.x 
No 
 
 
 
Xxxx 
xx.x 
xx 
xx.x 
xx.x 
No 
 
 
 
Xxxx 
xx.x 
xx 
xx.x 
xx.x 
No 
 
 
 
Xxxx 
xx.x 
xx 
xx.x 
xx.x 
No 
 
Cycle 1 Day 1 DDMMMYYYY/hh:mm 
Xxxx 
xx.x 
xx 
xx.x 
xx.x 
No 
 
 
 
Xxxx 
xx.x 
xx 
xx.x 
xx.x 
No 
 
 
 
Xxxx 
xx.x 
xx 
xx.x 
xx.x 
Yes 
 
 
 
Xxxx 
xx.x 
xx 
xx.x 
xx.x 
No 
 
CS: Clinically Significant; EOT: End of Treatment; Clinical significance is applicable if results are out of reference range; LLN: Lower Limit of Normal; ULN: Upper Limit of Normal; 
AE: Adverse Event. 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 
Use same format for 
Listing 16.2.8.2.2 Abnormal Laboratory Values – Biochemistry – Safety Analysis Set 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 89 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.8.3.1 
Clinical Laboratory Evaluations - Urinalysis 
Safety Analysis Set 
 
 
Patient 
ID 
Treatment Group 
Visit 
 
Date/Time of 
Collection 
Test Name 
 
Result 
 
Unit 
 
Normal/Abnormal 
In case of CS, Specify 
AE No 
 
Xxxx 
Xxxxx 
Screening 
DDMMMYYYY/ hh:mm xxxx 
xx.x 
xx 
Normal 
 
 
 
 
xxxx 
xx.x 
xx 
Normal 
 
 
 
 
xxxx 
xx.x 
xx 
Abnormal, NCS 
 
 
 
 
xxxx 
xx.x 
xx 
Normal 
 
 
 
 
xxxx 
xx.x 
xx 
Normal 
 
 
 
 
xxxx 
xx.x 
xx 
Normal 
 
 
NCS: Not Clinically significant; CS: Clinically Significant 
 
 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 90 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.8.3.2 
Abnormal Laboratory Values - Urinalysis 
Safety Analysis Set 
Patient 
ID 
Treatment Group 
Visit 
 
Date/Time of 
Collection 
 
Test Name 
 
Result 
 
Unit 
 
Clinically 
Significant? 
In case of CS, Specify 
AE No 
Xxxx 
Xxxxx 
xxxx 
DDMMMYYYY/ hh:mm 
xxxx 
xxxx 
xxxx 
No 
 
xxxx 
DDMMMYYYY/ hh:mm 
xxxx 
xxxx 
xxxx 
No 
 
xxxx 
DDMMMYYYY/ hh:mm 
xxxx 
xxxx 
xxxx 
No 
 
 
 
xxxx 
xxxx 
xxxx 
No 
 
 
 
xxxx 
xxxx 
xxxx 
No 
 
xxxx 
DDMMMYYYY/ hh:mm 
xxxx 
xxxx 
xxxx 
No 
 
 
 
 
 
 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 91 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.8.4 
Pregnancy Test 
Safety Analysis Set 
 
 
Patient 
ID 
Treatment Group 
Type of test 
Visit 
Date test performed 
Result 
Reason for the test not performed 
Xxxx 
Xxxxx 
Serum 
xxxx 
DDMMMYYYY 
Negative 
 
Xxxx 
Xxxxx 
Serum 
xxxx 
DDMMMYYYY 
Negative 
 
 
Urine 
xxxx 
 
 
xxxxx 
 
 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 92 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.9.1 
Vital Signs 
Safety Analysis Set 
 
 
 
 
 
 
 
 
 
Patient 
ID 
Treatment 
Group 
Visit 
Date/Time of Examination 
Weight (kg) 
Systolic 
Blood 
Pressure 
(mmHg) 
Diastolic 
Blood 
Pressure 
(mmHg) 
 
Pulse 
(beats/min) 
Respiratory 
Rate 
(breaths/min) 
Body 
Temperature 
(C) 
If Abnormal 
Clinically 
Significant /Det
ails 
Reason 
Vital Signs 
not taken 
xxxx 
Xxxxxx 
Screening 
DDMMMYYYY/hh:mm   
xx 
xx 
xx 
 xx 
xx 
xx 
 
 
Cycle 1 Day 1 DDMMMYYYY/hh:mm  
xx 
xx 
xx 
 xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 Vitals is collected at Pre-dose during treatment visits 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 93 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.9.2 
Abnormal Clinically Significant Vital Signs Values 
Safety Analysis Set 
 
 
 
 
 
 
 
 
 
 
 
Patient 
ID 
Treatment 
Group 
Visit 
Date/Time of Examination 
Weight (kg) 
Systolic 
Blood 
Pressure 
(mmHg) 
Diastolic 
Blood 
Pressure 
(mmHg) 
 
Pulse 
(beats/min) 
Respiratory 
Rate 
(breaths/min) 
Body 
Temperature 
(C) 
If Abnormal Clinically 
Significant /Details 
xxxx 
Xxxxxx 
Screening 
DDMMMYYYY/hh:mm   
xx 
xx 
xx 
 xx 
xx 
xx 
 
 
Cycle 1 Day 1 DDMMMYYYY/hh:mm  
xx 
xx 
xx 
 xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 Vitals is collected at Pre-dose during treatment visits 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 94 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.10.1 
Physical Examination at Screening 
Safety Analysis Set 
 
 
 
Patient       
ID             
Treatment 
Group 
Date of Examination 
System 
System 
response 
Specify Abnormal clinically significant If  Not Done, Reason for not 
Performed 
 
xxxx 
Xxxxxxx 
DDMMMYYYY 
Xxxx 
Normal 
 
 
 
 
 
 
Xxxx 
Not Done 
 
 
 
 
 
 
Xxxx 
Normal 
 
 
 
 
 
 
Xxxx 
Normal 
 
 
 
 
 
 
Xxxx 
Abnormal, NCS  
 
 
 
 
 
 
 
 
 
 
NCS: Not Clinically Significant; CS: Clinically Significant. 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 95 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Protocol RP6530-2101 
 
Page xx of yy 
Listing 16.2.10.2 
Follow up Abnormal Physical Examination Results 
Safety Analysis Set 
 
 
 
Patient 
ID 
Treatment Group 
Visit 
Date of Examination 
System 
System 
response 
Specify Abnormal 
clinically significant  
 Clinically significant compared to 
Screening 
xxxx 
Xxxxxx 
xxxx 
DDMMMYYYY 
Xxxx 
xxxx 
 
Yes 
 
xxxx 
DDMMMYYYY 
Xxxx 
xxxx 
 
 
 
xxxx 
DDMMMYYYY 
Xxxx 
xxxx 
 
No 
 
xxxx 
DDMMMYYYY 
Xxxx 
xxxx 
 
 
 
NCS: Not Clinically Significant; CS: Clinically Significant. 
 
 
 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 96 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
 
Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.11.1 
12-Lead ECG Results 
Safety Analysis Set 
 
 
 
Patient 
ID 
Treatment Group 
Visit 
Date/Time of ECG 
ECG Test 
Result 
Unit 
Interpretation 
Abnormality 
Details 
Reason 
ECG not 
performed 
xxxx 
Xxxxxx 
Screening 
DDMMMYYYY   
hh:mm 
PR Interval 
xxx.xx 
sec 
Normal 
 
 
 
 
 
Heart Rate 
xxx.xx 
beats/min Abnormal, NCS 
xxxxxx 
 
 
 
 
QT Interval 
xxx.xx 
msec 
Normal 
 
 
 
 
 
QTcF Interval 
xxx.xx 
msec 
 
 
 
 
 
 
QRS Duration 
xxx.xx 
msec 
 
 
 
 
ECG is collected at Pre-dose during treatment visits 
NCS: Not Clinically Significant, CS: Clinically Significant 
 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 97 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.11.2 
Abnormal ECG Values 
Safety Analysis Set 
Patient 
ID 
Treatment Group 
Visit 
Date/Time of ECG 
ECG Test 
Result 
Unit 
Clinically 
significant? 
Abnormality Details 
xxxx 
Xxxxxx 
xxxx 
DDMMMYYYY   
hh:mm 
PR Interval 
xxx 
xxx 
No 
xxxx 
 
 
 
Heart Rate 
xxx 
xxx 
No 
xxxx 
 
 
 
QT Interval 
xxx 
xxx 
No 
xxxx 
 
 
 
QTcF Interval 
xxx 
xxx 
No 
xxxx 
 
 
 
QRS Duration 
xxx 
xxx 
No 
xxxx 
 
 
 
 
 
 
 
xxxx 
DDMMMYYYY   
hh:mm 
xxxx 
xxx 
xxx 
No 
xxxx 
ECG is collected at Pre-dose during treatment visits 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 98 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Protocol RP6530-2101 
Page xx of yy 
Listing 16.2.12.1 
Comment Log 
All Patients 
 
Patient ID 
Visit 
Form  
Comment 
xxxx 
xxxx 
Xxxx 
xxxx 
 
xxxx 
Xxxx 
xxxx 
xxxx 
xxxx 
Xxxx 
xxxx 
 
 
EOT: End of Treatment. 
 
Program: xx.sas Listing Generation: ddmmmyyyy hh:mm:ss 
 
 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 99 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Protocol RP6530-2101 
Page xx of yy 
Figure 14.1.6.2 
Duration of Treatment plot 
Safety Analysis Set 
 
 
Duration of Treatment = Date of Last Dose - Date of First Dose + 1. 
The Best Overall Response (BOR) is defined as the best visit response recorded from the start of the treatment until disease progression/recurrence. For the patients without any post-
baseline efficacy assessment, BOR is considered as 'Not evaluated'. 
For SD ≥24 weeks, patients with treatment duration ≥168 (±7) days are summarized. 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 100 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Reference Listing 16.2.x.x 
Program: xx.sas Figure Generation: ddmmmyyyy hh:mm:ss 
<Note to Programmer>  
• 
Add categories as CR, PR, SD≥24 weeks, SD<4 weeks, PD, No response 
• 
Please present this plot by descending frequency of duration (i.e. maximum frequency (on top) to minimum frequency (at the bottom)) 
• 
There should be colour coding as per the best response (CR, PR, PD, etc), for all bars and a legend describing the same. 
• 
Please include the “No response” category when there is no response available for any patient. 
 
• 
Figure 14.1.6.3 Duration of treatment plot by metastasis type – Safety Analysis Set  
o 
This will be same as 14.1.6.2. The y-axis will be updated to display type of metastasis/patient ID. 
 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 101 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
 
Protocol RP6530-2101 
Page xx of yy 
Figure 14.2.3.4 
Kaplan-Meier plot for PFS 
ITT Analysis Set 
 
 
The Intent-to-Treat (ITT) analysis set includes all patients who received at least 1 dose of study medication. 
Median is calculated using Kaplan-Meier Estimate method. 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 102 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Time to Progression Free Survival (PFS) is defined as the time from the first dose of the study drug to documented disease progression or death due to any cause. For Patients who 
neither progress nor die, the duration of response is censored on the last date the patient is known to be radiologically progression free. 
Both the treatment groups are collectively used to represent the Overall group. 
Patients qualifying in Intent-to-Treat (ITT) and Per-Protocol (PP) analysis sets are identical. 
 
Program: xx.sas Figure Generation: ddmmmyyyy hh:mm:ss 
 
 
<Note to Programmer>  
In the first page plot will be by treatment groups and next page by overall. 
 
Use same format for 
1. Figure 14.2.3.5 Kaplan-Meier plot for PFS – Per Protocol Analysis 
 
 
 
 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 103 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
  
Protocol RP6530-2101 
Page xx of yy 
Figure 14.2.2.4 
Best Response (% change from Baseline) in sum of lesion diameters plot 
ITT Analysis Set 
 
 
 
The Best Overall Response (BOR) is defined as the best visit response recorded from the start of the treatment until disease progression/recurrence. 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 104 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
Best change from baseline represents the smallest value of change from baseline in sum of lesion diameter among all the visits. 
Patients with at least 1 post-baseline efficacy assessment are considered. 
Patients qualifying in Intent-to-Treat (ITT) and Per-Protocol (PP) analysis sets are identical. 
CR: Complete Response; PR: Partial Response; SD: Stable Disease; PD: Progressive Disease. 
 
 
Use same format for 
1. Figure 14.2.2.5 Best Response (% change from Baseline) in sum of lesion diameters plot – Per Protocol Analysis 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 105 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
 
Protocol RP6530-2101 
Page xx of yy 
Figure 14.2.2.6 
Visit Wise Tumor Response Plot 
ITT Analysis Set 
 
 
 
 
% Change from Baseline=((Sum of Lesions Diameter at Visit – Sum of Lesions Diameter at Screening)/Sum of Lesions Diameter at Screening)x100. 
Patients with at least 1 post-baseline efficacy assessment are considered. 
Patients qualifying in Intent-to-Treat (ITT) and Per-Protocol (PP) analysis sets are identical. 
 


 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Sponsor Name: Rhizen Pharmaceuticals AG 
Sponsor Protocol ID: RP6530-2101 
Labcorp Drug Development Study ID: 000000223291. 
 
CONFIDENTIAL 
Page 106 of 106 
Document Date: 12MAY2023. 
 
ST-AD-032 version 01 
 
 
<Note to Programmer>  
In the first page plot will be by treatment groups and next page by overall. 
 
 
 
Use same format for 
1. Figure 14.2.2.7 Visit Wise Tumor Response Plot – Per Protocol Analysis