Advanced Solid TumorPhase 1NCT05878691
A Study of GRC 54276 in Participants With Advanced Solid Tumors and Lymphomas.
A Phase 1 study testing GRC 54276, GRC 54276 + Pembrolizumab and GRC 54276 + Atezolizumab in people with Advanced Solid Tumor and Lymphoma, run by Glenmark Specialty S.A. at 18 sites in 2 countries.
Trial summary
This is first in human (FIH) study to a) evaluate the safety and tolerability profile of GRC54276, b) determine the maximum tolerated dose (MTD) and recommended Phase 2 doses (RP2D), and c) pharmacokinetic profile of GRC54276 alone and in combination with pembrolizumab or atezolizumab in participants with advanced… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor, Lymphoma
- What is being tested?
- GRC 54276, GRC 54276 + Pembrolizumab and GRC 54276 + Atezolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 320 participants
- Where
- 18 sitesin 2 countries
- Study dates
- 28 Jun 2022to 30 Jul 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects (≥18 years of age) with histologically or cytologically confirmed advanced, metastatic, unresectable solid tumors or lymphomas who have previously received standard systemic therapy or for whom treatment is not accessible, not tolerated or refused, have progressed after ≥1 of systemic therapies for recurrent/metastatic disease and who have not received prior therapy targeting HPK1.
- At least 1 measurable lesion as defined per RECIST 1.1. The target lesion(s) selected have not been previously treated with local therapy or the target lesion(s) selected that are within the field of prior local therapy have subsequently progressed as defined by RECIST 1.1.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1 measured within 72 hours of treatment.
- Predicted life expectancy of ≥3 months.
- Adequate organ function as indicated by the following laboratory values up to first dose of study drug: Hemoglobin ≥9.0 g/dL, Absolute neutrophil count ≥1.5 x 109/L, Serum total bilirubin ≤1.5 x ULN (<3 x ULN for participants with Gilbert syndrome), AST and ALT ≤2.5 x ULN (≤5 x ULNs for participants with hepatocellular carcinoma or liver metastases).
- Adequate renal function as indicated by creatinine clearance of ≥60mL/min calculated using Cokroft-Gault method.
- Adequate cardiac function, left ventricular ejection fraction (LVEF) of ≥50% as assessed by multi-gated acquisition (MUGA) or ultrasound/echocardiography (ECHO).
- For Part 2, dose expansion cohorts inclusion criteria specific to tumor types will be updated after completion of Part 1.
Who cannot join
- Any condition that, in the opinion of the Investigator, would interfere with evaluation of the study drug or interpretation of subject safety or study results.
- Subjects with uncontrolled or untreated brain metastasis or leptomeningeal disease. Subjects with equivocal findings or with confirmed brain metastases are eligible provided that they are asymptomatic and radiologically stable without the need for corticosteroid treatment for at least 4 weeks prior to the first dose of study drug(s)
- Any active malignancy ≤2 years before the first dose of study drug(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast)
- Any condition that required systemic treatment with either corticosteroids (>10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤14 days before the first dose of study drug(s), with the following exceptions:
- Adrenal replacement steroid (dose ≤10 mg daily of prednisone or equivalent)
- Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption
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- Short course (≤7 days) of corticosteroid prescribed prophylactically (e.g., for contrast dye allergy) or for the treatment of a non-autoimmune condition (e.g., delayed-type hypersensitivity reaction caused by contact allergen)
- Pregnant/planning to be pregnant or breast-feeding women.
- Any important medical illness or abnormal laboratory finding that would increase the risk of participating in this study (based on the investigator's judgment).
- Any known severe allergic reaction to pembrolizumab/atezolizumab or its excipients.
Trial locations and contacts
18 sites in 2 countries.
18 sites in 2 countries
India16 sites
Krupamayi Hospitals
Aurangabad, Maharashtra, 431001
Health Care Global Enterprises Ltd (HCG)
Bangalore, Karnataka, 5600027
Vydehi Hospital
Bangalore, Karnataka, 560066
Cytecare Hospitals Pvt Ltd.
Bengaluru, Karnataka, 560064
Aster CMI Hospital
Bengaluru, Karnataka, 560092
Max Superspeciality Hospital
Delhi, 110017
Artemis Hospital
Gurgaon, Haryana, 122001
AIG Hospitals, (A unit of asian Institute of Gastroenterology)
Hyderabad, Telangana, 500032
Basavatarakam Indo American Cancer Hospital Research Institute
Hyderabad, Telangana, 500034
Malabar Cancer Centre
Kannur, Kerala, 670103
PD Hinduja Hospital and Medical Research Centre
Mumbai, Maharashtra, 400052
HCG Manavata Cancer Centre
Nashik, Maharashtra, 422002
Sankalp Hospital
Nashik, Maharashtra, 422009
Bhaktivedanta Hospital and Research Institute
Thane, Maharashtra, 401107
Hcg City Cancer Centre
Vijayawada, Andhra Pradesh, 520002
Mahatma Gandhi Cancer Hospital and Research Institute
Visakhapatnam, Andhra Pradesh, 530017
United States2 sites
Carolina BioOncology Institute
Huntersville, North Carolina, 28078
Froedtert & Medical College of Wisconsin - Froedtert Hospital - Clinical Cancer Center
Milwaukee, Wisconsin, 53226-1222
About this study
Official title: A Phase 1, Open Label First In Human Study Investigating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of HPK1 Inhibitor GRC 54276 Alone and in Combination With Anti-PD-1 Monoclonal Antibody Pembrolizumab or Anti-PD-L1 Atezolizumab in Subjects With Advanced Solid Tumors and Lymphomas.
This is first in human (FIH) study to a) evaluate the safety and tolerability profile of GRC54276, b) determine the maximum tolerated dose (MTD) and recommended Phase 2 doses (RP2D), and c) pharmacokinetic profile of GRC54276 alone and in combination with pembrolizumab or atezolizumab in participants with advanced solid tumors and lymphomas.
- Conditions
- Advanced Solid Tumor, Lymphoma
- Being tested
- GRC 54276, GRC 54276 + Pembrolizumab, GRC 54276 + Atezolizumab
- Keywords
- Solid tumor, Lymphoma, MTD
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GRC 54276Drug
Part 1a: GRC 54276 QD will be administered orally from Day 1 to Day 21 in a 21-day treatment cycle.
Part 2: GRC 54276 monotherapy therapy will commence after establishment of the MTD and/or RP2D for monotherapy arm.
GRC 54276 + PembrolizumabDrug
Part 1b: GRC 54276 QD will be administered orally in combination with fixed dose of pembrolizumab IV every 21 days.
Part 2: GRC 54276 in combination with pembrolizumab will commence after establishment of the MTD and/or RP2D for combination therapy arm.
GRC 54276 + AtezolizumabDrug
Part 1b: GRC 54276 QD will be administered orally in combination with fixed dose of atezolizumab IV every 21 days.
Part 2: GRC 54276 in combination with atezolizumab will commence after establishment of the MTD and/or RP2D for combination therapy arm.
| Study group | Role | What they receive |
|---|---|---|
| GRC 54276 | Experimental | Not described Receives: Drug: GRC 54276 |
| GRC 54276 with pembrolizumab | Experimental | Not described Receives: Drug: GRC 54276 + Pembrolizumab |
| GRC 54276 with atezolizumab | Experimental | Not described Receives: Drug: GRC 54276 + Atezolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicities to establish the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D)
Percentage of participants with dose limiting toxicities associated with GRC54276 alone or GRC54276 combined with pembrolizumab or atezolizumab during the first cycle. Toxicity will be assessed using the NCI CTCAE Version 5.0.
Measured: 18 weeks
Incidence of treatment-emergent adverse events and serious adverse events
Percentage of participants who experience treatment-emergent adverse events and serious adverse events when given GRC54276 as a single agent and in combination with pembrolizumab or atezolizumab.
Measured: up to 120 days
Changes in the laboratory safety values from baseline to end of safety follow-up
Percentage of participants who experience changes in the laboratory safety values when given GRC54276 as a single agent and in combination with pembrolizumab or atezolizumab.
Measured: up to 120 days
Pharmacokinetic profile of GRC54276- Maximum plasma concentration (Cmax)
The maximum measured plasma concentration after single or multiple dosing, tabulated by dose group and day of dosing.
Measured: up to 22 days
Pharmacokinetic profile of GRC54276- Time to Cmax (Tmax)
The time to achieve Cmax after single or multiple dosing, tabulated by dose group and day of dosing.
Measured: up to 22 days
Pharmacokinetic profile of GRC54276- Area under the curve (AUC)
Area under plasma concentration versus time curve from time 0 to time of least measurable concentration or the dosing interval, tabulated by dose group and day of dosing.
Measured: up to 22 days
Secondary outcomes (4)
Objective response rate (ORR)
Proportion of participants with a best response of complete response or partial response best on RECIST 1.1.
Measured: up to 9 months
Best overall response rate
Complete response, partial response, stable disease, and progressive disease, evaluated according to RECIST 1.1.
Measured: up to 9 months
Disease control rate
The percentage of participants who have achieved stable disease or complete response or partial response according to RECIST 1.1. for the entire duration of the study.
Measured: up to 9 months
Duration of response
The time from first documentation of complete response or partial response to the first documentation of progression.
Measured: up to 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2023
- Study start28 Jun 2022
- Primary completion30 Jul 2027 (estimated)
- Study completion30 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 320 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Glenmark Specialty S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Veena Gupta, Study director, Glenmark Pharmaceuticals Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05878691
- Sponsor's protocol ID
- GRC 54276-101
- Other IDs
- CTRI/2022/05/042484
- Status last verified
- Jul 2024
- First submitted
- 19 May 2023
- Last updated
- 22 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open Label First In Human Study Investigating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of HPK1 Inhibitor GRC 54276 Alone and in Combination With Anti-PD-1 Monoclonal Antibody Pembrolizumab or Anti-PD-L1 Atezolizumab in Subjects With Advanced Solid Tumors and Lymphomas.
- ClinicalTrials.gov ID
- NCT05878691
- Acronym / sponsor ID
- GRC 54276-101
- Conditions
- Advanced Solid Tumor, Lymphoma
- Keywords
- Solid tumor, Lymphoma, MTD
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 320 participants (estimated)
- Lead sponsor
- Glenmark Specialty S.A.Industry (pharma, biotech, devices)
- Study start
- 28 Jun 2022 (actual)
- Primary completion
- 30 Jul 2027 (estimated)
- Study completion
- 30 Jul 2027 (estimated)
- First posted
- 26 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is first in human (FIH) study to a) evaluate the safety and tolerability profile of GRC54276, b) determine the maximum tolerated dose (MTD) and recommended Phase 2 doses (RP2D), and c) pharmacokinetic profile of GRC54276 alone and in combination with pembrolizumab or atezolizumab in participants with advanced solid tumors and lymphomas.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| GRC 54276 | Experimental | Drug: GRC 54276 |
| GRC 54276 with pembrolizumab | Experimental | Drug: GRC 54276 + Pembrolizumab |
| GRC 54276 with atezolizumab | Experimental | Drug: GRC 54276 + Atezolizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Subjects (≥18 years of age) with histologically or cytologically confirmed advanced, metastatic, unresectable solid tumors or lymphomas who have previously received standard systemic therapy or for whom treatment is not accessible, not tolerated or refused, have progressed after ≥1 of systemic therapies for recurrent/metastatic disease and who have not received prior therapy targeting HPK1.
- At least 1 measurable lesion as defined per RECIST 1.1. The target lesion(s) selected have not been previously treated with local therapy or the target lesion(s) selected that are within the field of prior local therapy have subsequently progressed as defined by RECIST 1.1.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1 measured within 72 hours of treatment.
- Predicted life expectancy of ≥3 months.
- Adequate organ function as indicated by the following laboratory values up to first dose of study drug: Hemoglobin ≥9.0 g/dL, Absolute neutrophil count ≥1.5 x 109/L, Serum total bilirubin ≤1.5 x ULN (<3 x ULN for participants with Gilbert syndrome), AST and ALT ≤2.5 x ULN (≤5 x ULNs for participants with hepatocellular carcinoma or liver metastases).
Key exclusion criteria (10 listed)
- Any condition that, in the opinion of the Investigator, would interfere with evaluation of the study drug or interpretation of subject safety or study results.
- Subjects with uncontrolled or untreated brain metastasis or leptomeningeal disease. Subjects with equivocal findings or with confirmed brain metastases are eligible provided that they are asymptomatic and radiologically stable without the need for corticosteroid treatment for at least 4 weeks prior to the first dose of study drug(s)
- Any active malignancy ≤2 years before the first dose of study drug(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast)
- Any condition that required systemic treatment with either corticosteroids (>10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤14 days before the first dose of study drug(s), with the following exceptions:
- Pregnant/planning to be pregnant or breast-feeding women.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GRC 54276Part 1a: GRC 54276 QD will be administered orally from Day 1 to Day 21 in a 21-day treatment cycle. Part 2: GRC 54276 monotherapy therapy will commence after establishment of the MTD and/or RP2D for monotherapy arm. | Drug | GRC 54276 |
| GRC 54276 + PembrolizumabPart 1b: GRC 54276 QD will be administered orally in combination with fixed dose of pembrolizumab IV every 21 days. Part 2: GRC 54276 in combination with pembrolizumab will commence after establishment of the MTD and/or RP2D for combination therapy arm. | Drug | GRC 54276 with pembrolizumab |
| GRC 54276 + AtezolizumabPart 1b: GRC 54276 QD will be administered orally in combination with fixed dose of atezolizumab IV every 21 days. Part 2: GRC 54276 in combination with atezolizumab will commence after establishment of the MTD and/or RP2D for combination therapy arm. | Drug | GRC 54276 with atezolizumab |
Primary outcome
Dose limiting toxicities to establish the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D)
Time frame: 18 weeks
Percentage of participants with dose limiting toxicities associated with GRC54276 alone or GRC54276 combined with pembrolizumab or atezolizumab during the first cycle. Toxicity will be assessed using the NCI CTCAE Version 5.0.
Incidence of treatment-emergent adverse events and serious adverse events
Time frame: up to 120 days
Percentage of participants who experience treatment-emergent adverse events and serious adverse events when given GRC54276 as a single agent and in combination with pembrolizumab or atezolizumab.
Changes in the laboratory safety values from baseline to end of safety follow-up
Time frame: up to 120 days
Percentage of participants who experience changes in the laboratory safety values when given GRC54276 as a single agent and in combination with pembrolizumab or atezolizumab.
Pharmacokinetic profile of GRC54276- Maximum plasma concentration (Cmax)
Time frame: up to 22 days
The maximum measured plasma concentration after single or multiple dosing, tabulated by dose group and day of dosing.
Pharmacokinetic profile of GRC54276- Time to Cmax (Tmax)
Time frame: up to 22 days
The time to achieve Cmax after single or multiple dosing, tabulated by dose group and day of dosing.
Pharmacokinetic profile of GRC54276- Area under the curve (AUC)
Time frame: up to 22 days
Area under plasma concentration versus time curve from time 0 to time of least measurable concentration or the dosing interval, tabulated by dose group and day of dosing.
4 secondary outcomes
Objective response rate (ORR)
Time frame: up to 9 months
Best overall response rate
Time frame: up to 9 months
Disease control rate
Time frame: up to 9 months
Duration of response
Time frame: up to 9 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Veena Gupta study director
Glenmark Pharmaceuticals Ltd.
18 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GRC 54276, GRC 54276 + Pembrolizumab and GRC 54276 + Atezolizumab in people with Advanced Solid Tumor and Lymphoma, run by Glenmark Specialty S.A. at 18 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 22 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in India, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting toxicities to establish the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D) (time frame: 18 weeks). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2024; AzTrials last refreshed its copy on 7 Nov 2026.