| CTRI Number |
CTRI/2024/07/070802 [Registered on: 18/07/2024] Trial Registered Prospectively |
| Last Modified On: |
26/09/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Single Arm Study |
|
Public Title of Study
|
First in Human Multicenter Open Name Dose-increase,Consolidation method to Study Safety drug-level in Blood & drug metabolism Clinical Activity of Oral JBI-778 in Lung Cancer Patients with, without Brain Metastasis IDH Mutated WHO Grade 3,4 Recurrent Glioma, Salivary glands tumor |
|
Scientific Title of Study
|
A Phase 1, Multicenter, Open-Label, Dose-Escalation/Consolidation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of Orally Administered JBI-778 in EGFR Mutated Lung Cancer Patients with or without Brain Metastasis, Isocitrate Dehydrogenase (IDH) Mutated WHO Grade 3/4 Recurrent Glioma and Adenoid Cystic Carcinoma (ACC) |
| Trial Acronym |
Nil |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| JBI-778-101 ,Final Version 1.0; Dated 20 Nov 2023 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Kumar Prabhash |
| Designation |
Professor and Head Of Department |
| Affiliation |
Tata Memorial Centre |
| Address |
Tata Memorial Centre
Room number 1108, Homi Bhabha Block,
Tata Memorial Hospital, Dr. Ernest Borges Road,
Parel, Mumbai – 400012
Mumbai
MAHARASHTRA
400012
India |
| Phone |
9167760576 |
| Fax |
|
| Email |
kprabhash1@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Sridharan Rajagopal |
| Designation |
Vice President Site Head, JTIL |
| Affiliation |
Jubilant Therapeutics India Limited |
| Address |
96 Industrial Suburb Bangalore 560022 Karnataka India
Bangalore
KARNATAKA
560022
India |
| Phone |
9591400922 |
| Fax |
|
| Email |
Sridharan.Rajagopal@jubilanttx.com |
|
Details of Contact Person
Public Query
|
| Name |
Shawnavaz Vazeer |
| Designation |
Associate Director Project Management |
| Affiliation |
Jubilant Therapeutics India Limited |
| Address |
96 Industrial Suburb Bangalore 560022 Karnataka India
Bangalore
KARNATAKA
560022
India |
| Phone |
9930441048 |
| Fax |
|
| Email |
Shawnavaz.Vazeer@jubilanttx.com |
|
|
Source of Monetary or Material Support
|
| Jubilant Therapeutics India Limited
96 Industrial Suburb,2nd Stage Yeswanthpur,Bangalore,560022,Karnataka, India
|
|
|
Primary Sponsor
|
| Name |
Jubilant Therapeutics India Limited |
| Address |
1A, Sector 16A, Noida - 201 301, Uttar Pradesh, India |
| Type of Sponsor |
Other [Biotech] |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 8 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Prabhat Mallik |
All India Institute of Medical Sciences(AIIMS) |
Sri Aurobindo Marg, Ansari Nagar, Ansari Nagar East, New Delhi, Delhi 110029
New Delhi
DELHI |
9968325318
drprabhatsm@gmail.com |
| Dr Priya Tiwari |
Artemis Hospital |
Sector 51 Gurugram Haryana - 122001
Gurgaon
HARYANA |
8377828241
priya.tiwari@artemishospitals.com |
| Dr Kandappan Velavan |
Erode Cancer Centre Private Limited |
1-393, velavan nagar, Perundurai road, thindal post Erode Tamil Nadu -638012
Erode
TAMIL NADU |
9842334222
drvelavank@gmail.com |
| Dr Raj Nagarkar |
HCG Manavata Cancer Centre |
Behind Shivang auto, Mumbai nakka Nashik Maharashtra - 422002
Nashik
MAHARASHTRA |
9823061929
drraj@manavatacancercentre.com |
| Dr Priyal Dhameliya |
Kiran Super Multi-Speciality Hospital. |
Vasta Devdi Road, Near Sumul Dairy Katargam, Surat 395004 GUJARAT
Surat
GUJARAT |
9428638448
drpriyalrsavaliya@gmail.com |
| Dr Anil Kumar MR |
Oncoville Cancer Hospital and Research Center |
No. 4, 80ft road, 7 block, nagarbhavi 2 stage Bangalore Karnataka - 560072
Bangalore
KARNATAKA |
9739808502
dranil.onco@gmail.com |
| Dr Vijay Patil |
SunAct Cancer Institute Pvt Ltd. |
4th floor, Tieten Medicity Hospital, Sunact Cancer Insti-tute Pvt. Ltd, Ghodbunder Rd, Kasarvadavali, Thane West, Thane, Maharashtra 400615
Thane
MAHARASHTRA |
9136129135
vijaypgi@gmail.com |
| Dr Kumar Prabhash |
Tata Memorial Center |
11 floor, Homi Bhabha block, tata memorial hospital, Dr Ernest Borges road, Parel Mumbai Maharashtra - 400012
Mumbai
MAHARASHTRA |
9167760576
kprabhash1@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 8 |
| Name of Committee |
Approval Status |
| Artemis Health Sciences Institutional Ethics Committee |
Approved |
| Institutional Ethics Committee All India Institute Of Medical Sciences |
Approved |
| Institutional Ethics Committee of Oncoville Cancer Hospital and Research Centre Oncoville Cancer Hospital and Research Centre |
Approved |
| Institutional Ethics Committee, Erode Cancer Centre |
Approved |
| Kiran Hospital Ethics Committee |
Approved |
| Manavata Clinical Research Institute Ethics Committee |
Approved |
| TMH, Institutional Ethics Committee-I |
Approved |
| Vedant Hospital Institutional Ethical Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C399||Malignant neoplasm of lower respiratory tract, part unspecified, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
JBI-778 Oral Capsule
40 mg daily dose in 21-day continuous cycles
Once daily dosing in repeated 21-day cycles. JBI-778
capsule is taken orally with water approximately same time
either 1 hour before a meal or 2 hours after a meal
|
PRMT5 inhibitors
The starting dose of the study drug is 40 mg/day. JBI-778 will be administered orally for 21-days
cycles. JBI-778 is taken orally with water under fasted conditions (approx. same time either 1 hour
before a meal or 2 hours after a meal). Patients will be provided a bottle containing a sufficient
number of capsules of JBI-778 for each Cycle as appropriate. The finished drug product is JBI778 in capsules with unit-dose strengths of 20, 100, or 250 mg. Based on the dose that patient is
assigned, the capsules from respective bottle will be taken by patient. The site personnel will
instruct patient on number of capsules to be taken from bottles
As one of the most promising anticancer targets in the PRMT family, PRMT5 has attracted
increasing attention, and many efforts have been put into developing its inhibitors. PRMT5 is a
significant epigenetic modifier of histone and non-histone proteins and its dysregulation is
associated with clinical features of various cancers. Targeting PRMT5 represents an excellent way
to combat cancers in an efficient and selective way. There would be development of an increasing
number of drugs targeting PRMT5, and the curative effect would improve, providing more means
and strategies for the treatment of PRMT5-related tumors in the future. PRMT5 has been
suggested as a therapeutic target in a variety of diseases including infectious disease, heart disease,
and cancer. Many PRMT5 inhibitors have been discovered in the past years and have entered
clinical trials for the treatment of solid tumor and mantle cell lymphoma (MCL). However, no
drug targeting PRMT5 is available yet in the market. Attempts have been made by other Pharma
organizations to test the PRMT5 inhibitors into the clinical setting (molecules like GSK3326595,
JNJ-64619178, and PF-06939999) targeting multiple hematopoietic and solid tumor
indications.
(10)
JBI-778 is one of the innovative molecules developed by Jubilant Therapeutics Inc.,
as a PRMT5 inhibitor with potentially high brain exposure that allows to target validated
mechanism in cancers with brain metastasis, as many current treatments do not have adequate
brain exposure. Based on the encouraging results from preclinical studies conducted by Sponsor,
the development program for this molecule has been focused on developing JBI-778 as a target
for the patients with advanced malignancy treatment in the proposed study.
|
| Comparator Agent |
Not Applicable |
Not Applicable |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
Males or females aged ≥ 18 years at the time of informed consent.
Screening laboratory values:
Absolute neutrophil count (ANC) ≥1,500 cells/mm3.
Platelet count ≥100,000 cells/mm3.
Total bilirubin ≤1.5× ULN (upper limit of normal). Patients with Gilbert’s
syndrome may be enrolled with up to 3.0×ULN.
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5×
ULN (unless liver metastases are present then up to ≤5×ULN is allowed).
Creatinine clearance (CrCL) ≥ 40 mL/min based on the Cockcroft-Gault
glomerular filtration rate estimation or other equally relevant calculations. (Refer
in Appendix VIII)
Prothrombin Time (PT) or Activated Partial Thromboplastin Time (aPTT) ≤1.5×
ULN if the patient is not on anticoagulants (If the patient is on anticoagulants, the
patient must be on a stable dose for at least 2-weeks prior to screening).
|
|
| ExclusionCriteria |
| Details |
Treatment with systemic anticancer therapy or an investigational agent within 2-weeks or
5 half-lives, whichever is shorter, prior to the start of study drug treatment.
Major surgery ≤ 21 days prior to starting study drug or has not recovered from adverse
effects of such procedure.
Surgery (e.g., stomach bypass) or medical condition that might significantly affect the
absorption of medicines (as judged by the investigator).
Radiotherapy within 4 week for brain metastases and 2-weeks for the rest of body part
prior to the start of study drug treatment. Patients must have recovered from all
radiotherapy-related toxicities prior to the start of study treatment.
Severe or unstable medical condition, such as congestive heart failure (New York Heart
Association [NYHA] Class III or IV), ischemic heart disease, uncontrolled hypertension,
uncontrolled diabetes mellitus, psychiatric condition, as well as an uncontrolled cardiac
arrhythmia requiring medication (≥ Grade 2, according to NCI CTCAE V5), myocardial
infarction within 6 months prior to starting study treatment, or any other significant or
unstable concurrent cardiac illness. Note: stable chronic atrial fibrillation is allowed.
|
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
Primary Endpoint
Incidence of dose-limiting toxicity (DLT)events during the DLT monitoring period.[Timeframe: Baseline through Day 21 of Cycle1].
|
[Timeframe: at 6 months and up to
approximately 2 years] |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
• Incidence of adverse events (AE)
characterized overall and by type, frequency,seriousness, relationship to study treatment,timing, and severity graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
• Changes in clinical laboratory parameters, vital signs, electrocardiogram (ECG) parameters, eye examination including slit lamp examination and physical examination. |
[Timeframe: up to approximately 2 years] |
PK profile as assessed by single-dose and
steady-state such as Cmax, tmax, AUC0-t,
AUCτ, AUC0-∞, and t½ etc.
• To assess exposure/QTc relationship |
[Timeframe: up to approximately 2 years] |
• Change from baseline in symmetrical dimethylarginine (SDMA) as a PD measure.
|
[Timeframe: up to approximately 2 years] |
IDH Mutated WHO Grade 3/4 Recurrent
Glioma
• Response rate by response assessment in
neuro-oncology (RANO)
• Progression free survival (median and
landmark) by RANO Overall survival
• Neurological assessment in neuro-oncology
(NANO) |
[Timeframe: up to approximately 2 years] |
Metastatic or advanced, incurable disease
arising from any primary site
Progression free survival by RECIST 1.1
• Investigator-assessed overall response rate
(ORR) and duration of response (DOR) as
defined by response evaluation criteria
(RECIST) Version 1.1.
• Overall survival
|
[Timeframe: at 6 months and up to
approximately 2 years] |
Brain Metastases and extracerebral disease
• Response rate by response assessment in
neuro-oncology brain metastases (RANO).
• Progression Free Survival for cerebral and
extracerebral disease by RANO and RECIST
1.1 respectively.
• Investigator-assessed ORR and DOR as
defined by response evaluation criteria in
solid tumors (RECIST) Version 1.1 for
extracerebral disease.
• Overall survival
• Neurologic assessment in neuro-oncology
(NANO)
|
[Timeframe: up to approximately 2 years]
|
EGFR Mutated Lung Cancer without
Brain Metastasis
• Progression free survival by RECIST 1.1
• Investigator-assessed ORR and DOR as
defined by response evaluation criteria
(RECIST) Version 1.1.
• Overall survival
|
[Timeframe: at 6 months and up to
approximately 2 years] |
|
|
Target Sample Size
|
Total Sample Size="42"
Sample Size from India="42"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 1 |
|
Date of First Enrollment (India)
|
26/08/2024 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="6"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
This is a phase 1, multicenter, first-in-human, open-label, dose-escalation/consolidation study to investigate the safety, pharmacokinetics, pharmacodynamics, and clinical activity of orally administered JBI-778 in EGFR mutated lung cancer patients with or without brain metastasis, IDH mutated WHO grade 3 /4 recurrent glioma and ACC with evidence of recurrent, metastatic or advanced, incurable disease arising from any primary site. A total of 42 patients will be recruited in the study. The initial dose escalation up to cohort 3 (estimate to be 160mg) or until the pharmacologically active dose is reached, whichever comes first as determined by the safety committee will be performed only in EGFR mutant NSCLC patients with or without stable cerebral metastases and ACC patients. Once this dose level is reached IDH mutant WHO grade 3 /4 glioma patients will be added. Once the RP2D is determined following dose escalation, additional patients, up to 12, will be treated at that dose to obtain further safety data and preliminary efficacy. Approximately 4 to 6 sites is anticipated for the dose-escalation/consolidation, additional sites will be evaluated as needed. Study will be initiated only after receipt of regulatory and ethics committee (EC) approval. After signing the informed consent form, the patients will undergo screening assessments to confirm eligibility. Eligible patients will be considered first for initial dose escalation and once the RP2D is determined following dose escalation, additional patients, up to 12, will be treated at that dose to obtain further safety data and preliminary efficacy. The RP2D will be establish after a detailed analysis of the totality of dose escalation data, including PK, safety, efficacy, CNS penetration based on CSF sample for study drug presence, analysis of PD markers in peripheral blood and both pre-treatment and on treatment tumor biopsies. The duration of participation for each patient will be as follows:
• Screening: - Up to 21 days (-21 to 1 days)
• Treatment period: Treatment cycle of 21-day each. Treatment may continue for up to 2
years from the start of treatment, provided that the patient experiences clinical benefit in
the opinion of the Investigator and shows no signs or symptoms of unequivocal progression
of the disease, unacceptable toxicity, or other reasons for study discontinuation.
• End of treatment (EOT)/ Early termination (ET) visit
• Safety Follow-up: 30 days after last dose
• Survival: Every 3 months |