SAFETY REPORTING PROCESS

An Independent and Internationally Accredited CRO

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Oregovomab Safety Profile

Oregovomab given as Monotherapy:

• Infusion-related reactions are the most common side effects known for the study
drug oregovomab when it is taken alone.
• Includes reactions such as flushing (warmth and reddening of skin), rash,
fever, rigors (feeling of cold with shivering), chills, shortness of breath, and
mild low blood pressure.
• Seen in 20% or more of the patients who received the drug in the past
• The majority of the cases, they were mild, easily managed and generally
prevented when pre-medications were taken by patients before they received
oregovomab.
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Safety of Oregovomab- Combination therapy

Approximately, 169 patients with ovarian cancer were studied with oregovomab chemoimmunotherapy in 4
company sponsored clinical studies; of these, 120 patients were treated with Oregovomab and 49 patients were
treated with placebo.

Parameter Chemoimmunotherapy Chemotherapy

At least one AE 93.3 % (112 patients) 85.7% (42 patients)

At least one SAE 22.5% (27 patients) 18.4% (9 patients)

Treatment Emergent Adverse Event 7.5% (9 patients) 18.4% (9 patients)

(both serious and non-serious leading to withdrawal)

Refer to IB for complete details

In Summary:
Oregovomab combination with carboplatin + paclitaxel in ovarian cancer, or with gemcitabine + radiotherapy in
pancreatic cancer has not contributed to additional unexpected adverse events.
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Summary of Treatment Emergent SAEs (> 1 Total both Treatment Groups) by Preferred Term for

Oregovomab Chemoimmunotherapy Studies (completed)- Reference- IB

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SAE Data from QPT-QRE-005

As of 15-Sep-2022,
• There are 115 SAEs reported.
• 5 of them are related to Oregovomab (of these, the SUSAR of Dehydration was experienced twice by
one subject).
SOC Number of Events
Gastrointestinal disorders 28
Infections and infestations 19
Blood and lymphatic system disorders 8
Investigations 8
General disorders and administration site conditions 7
Injury, poisoning and procedural complications 7
Vascular disorders 7
Respiratory, thoracic and mediastinal disorders 6
Nervous system disorders 5
Cardiac disorders 4
Metabolism and nutrition disorders 4
Renal and urinary disorders 4
Hepatobiliary disorders 2
Immune system disorders 2
Neoplasms benign, malignant and unspecified (incl cysts and polyps) 2
Musculoskeletal and connective tissue disorders 1
Skin and subcutaneous tissue disorders 1
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Adverse Events of Special Interest (AESI)

• Hypersensitivity reactions, particularly Infusion Related Reactions (IRR) appear to be most common Oregovomab related
adverse events and these must be treated and analyzed as AESIs.

Refer to IB for complete list of Signs/ Symptoms identified per System Organ Class (SOC) that could potentially be IRRs.

Important

1. Not all the listed signs/ symptoms qualify as AESIs. The latency of the event in related to administration time of

Oregovomab/ Paclitaxel/ Carboplatin must be considered while assessing AESIs.

2. The signs/ symptoms could be the result of a different adverse event/ medical condition and hence these must be assessed

in context before reporting/ recording these events as AESIs.

3. IRRs related to/ occurring after Paclitaxel and Carboplatin are not considered AESIs. They must be recorded/ reported as

regular AEs and SAEs as per the routine ICH and other regulatory guidelines.

4. When Oregovomab is given as monotherapy and if the events occur within the stipulated time, the causality is

automatically implied.
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Safety of Paclitaxel*
Bone marrow suppression
Primarily Neutropenia. Others include Leukopenia,
Thrombocytopenia, Anemia and Infections.
Gastro-intestinal toxicity
Nausea/ Vomiting, diarrhea and mucositis were
commonly reported. Usually mild to moderate.
Mucositis was more frequent with 24-hour infusion
rather than 3-hour infusion.
Neurotoxicity
Peripheral neuropathy- Paresthesia commonly
occurs in the form of hyperesthesia.
*-Reference- Paclitaxel injection, solution United States Prescribing
Information
Hypersensitivity Reactions
Anaphylaxis, Dyspnea, Angioedema and Generalized
urticaria. All patients must be pretreated with
corticosteroids, diphenhydramine and H2 antagonists.
Patients who experience severe hypersensitivity
reactions to paclitaxel should not be rechallenged.
Hepatotoxicity
Paclitaxel is metabolized in liver. Caution should be
exercised while administering Paclitaxel with known
substrates (midazolam, buspirone, felodipine,
lovastatin, eletriptan, sildenafil, simvastatin and
triazolam) and with known inhibitors (eg, atazanavir,
clarithromycin, indinavir, itraconazole, ketoconazole,
nefazodone, nelfinavir, ritonavir, saquinavir, and
telithromycin) and inducers (eg, rifampin and
carbamazepine).
Increase in Bilirubin could be the reason for dose
reduction.
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Safety of Carboplatin*
Bone marrow suppression Hypersensitivity Reactions
Primarily Thrombocytopenia. Myelosuppression is a Anaphylactic-like reactions have been reported within
dose-limiting toxicity. minutes of administration.

Gastro-intestinal toxicity
Severe vomiting and Nausea. Usually resolve within Hepatotoxicity
24 hours of treatment and responsive to anti- Blood alkaline phosphatase increased, aspartate
emetics. Others include diarrhea and constipation. aminotransferase increased

Neurotoxicity Nephrotoxicity
Peripheral neuropathy Creatinine clearance decreased, Blood urea decreased,
Abnormal Renal Function Tests- mild.

Electrolyte changes
Very common- Blood sodium decreased, Blood *- CARBOPLATIN- carboplatin injection, solution Hospira Inc- USPI
potassium decreased, Blood calcium decreased,
Blood magnesium decreased
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AE and SAE Recording/ Reporting

• The sites must use the format as specified in Table 5 of NDCT regulations to
report initial SAE to Veristat and Ethics Committees. SUGAM portal shall be used
to report to DCGI.
• Once the seriousness criteria is checked off for an event in the eCRF, the system
triggers an auto-notification to Veristat PV team via email. Veristat PV team will
contact the site to confirm the credibility and accuracy of the received
information.
• In the situations when EDC system is not working, use the paper SAE form
template to complete the information and send the scanned report via email
provided in the protocol.
• Patient’s medical records are not to be used as an alternative to the above methods
of reporting. There may be instances when copies of medical records for certain
cases are requested by the sponsor (or its designee). In this case, all patient
identifiers, except for the patient number, must be redacted on the copies of the
medical records before submission to the sponsor (or its designee).
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Reporting to Ethics Committees and DCGI

• It is the responsibility of the investigator to report all the SAEs to DCGI (via SUGAM
portal), to the to the Chairperson of IEC/IRB and to the sponsor’s Designee (Veristat)
and Raptim Research Pvt. Ltd. team within 24 hours of awareness regarding the
SAE.
• The investigator must also submit a detailed report after due analysis, to DCGI and
chairperson of IEC/IRB and to the head of institution where SAE occurred, within 14
days from the start date of the SAE.
• It is expected that the sites will follow their institutional procedures for fulfilling
the above responsibilities as stipulated by CDSCO/ DCGI.
• In case the clinical investigator fails to report any SAE within the stipulated period,
he/she shall furnish the reason for the delay to the satisfaction of DCGI (Drug
Controller General of India) along with report of SAE.
 CanariaBio SAE management Process

24 hrs. of
SAE Investigator informs all SAEs to Central Licensing Authority (DCGI) using SUGAM
occurrenc portal, and IRB/EC within 24 hours of their occurrence using Table-5 format of NDCT
e

Veristat PV receives SAE notification/report via email from the site

Veristat PV confirms validity of the

Veristat PV reviews SAE report
SAE Reporting form

Veristat PV enters SAE information Not

Valid
Day 0 into Safety Database Valid

Veristat PV acknowledges receipt to site and

pertinent study staff and, if applicable, requests
additional information via email. Veristat also Archive the invalid report
informs Raptim and CanariaBio PV regarding the
receipt of SAE

Veristat PV and/or CanariaBio PV team medically review, assess causality and expectedness
of SAE

Veristat PV drafts and sends narrative and draft CIOMS to

Day 7
CanariaBio PV for review and approval.

CanariaBio PV reviews, and approves narrative and draft

Day 8
CIOMS

Day 9 Veristat PV finalizes narrative, and CIOMS

In the event of SAE which involves death the

Veristat PV provides
approved narrative
Day 10 and CIOMS to
Raptim, and E2B R3
reports to IQVIA
Investigator will also send a copy of detailed
SAE report within calendar 10 days to
CDSCO, the chairman of expert committee
constituted by the CDSCO, EC and the head
of institute (where the SAE has occurred).

Raptim submits 14th day Due Analysis report and SAE

Narrative to DCGI (using SUGAM portal), IRB/EC, all
site investigators, head of the institution where the trial
has
Day 14
been conducted and Veristat.
NOTE- All teams to ensure to include only unblinded staff
from each team when sending unblinded reports

Veristat files narratives, CIOMS forms, 14-Day Due Analysis

Reports, Subsequent Follow-up Reports in eTMF and Safety
Database.
 PI Responsibilities For SAE Reporting
Irrespective of causality
Within 14 calendar days
Within 24 hours from knowledge of its occurrence Detailed SAE Report

DCGI via SUGAM

PI DCGI via SUGAM
PI EC
EC
Head of Institute
Veristat via email id
pharmacovigilanceOncoQuest@veristat.com Veristat via group mail id

Individual Safety Report (ISR) ISR to other participating sites

Within 14 calendar days of its occurrence
Veristat
At site where SAE occurred
Veristat
Raptim PI EC
Raptim PI EC

Head of
Head of Institute Institute
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Assessment of Action Taken with the study drug

The following options are available in EDC
• Drug on hold- To be used when subsequent cycles are put on hold due to AE/ SAE
• Dose not changed- To be used when there are no dose modifications due to the event.
• Dose reduced- To be used when dose is reduced in response to the event.
• Drug interrupted- To be used when the infusion was interrupted due to AE. Typically
applies to Infusion Related Reactions (IRR).
• Drug discontinued- To be used when the study drug(s) are permanently discontinued
due to the events.
• Not applicable- To be used when the event occurs prior to the start of study drug (From
ICF until the date of first study drug administration) or when the event occurs after
completion of all cycles of study drug administration