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A Study of GRC 54276 in Participants With Advanced Solid Tumors and Lymphomas.

Primary Purpose

Advanced Solid Tumor, Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
GRC 54276
GRC 54276 + Pembrolizumab
GRC 54276 + Atezolizumab
Sponsored by
Glenmark Specialty S.A.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Solid Tumor focused on measuring Solid tumor, Lymphoma, MTD

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. Exclusion Criteria: 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 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.

Sites / Locations

  • Carolina BioOncology Institute
  • Froedtert & Medical College of Wisconsin - Froedtert Hospital - Clinical Cancer Center
  • Artemis HospitalRecruiting
  • Health Care Global Enterprises Ltd (HCG)Recruiting
  • Vydehi HospitalRecruiting
  • Malabar Cancer CentreRecruiting
  • Krupamayi HospitalsRecruiting
  • HCG Manavata Cancer CentreRecruiting
  • Sankalp HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

GRC 54276

GRC 54276 with pembrolizumab

GRC 54276 with atezolizumab

Arm Description

Outcomes

Primary Outcome Measures

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.
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.
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.
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.
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.
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.

Secondary Outcome Measures

Objective response rate (ORR)
Proportion of participants with a best response of complete response or partial response best on RECIST 1.1.
Best overall response rate
Complete response, partial response, stable disease, and progressive disease, evaluated according to RECIST 1.1.
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.
Duration of response
The time from first documentation of complete response or partial response to the first documentation of progression.

Full Information

First Posted
May 19, 2023
Last Updated
July 6, 2023
Sponsor
Glenmark Specialty S.A.
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1. Study Identification

Unique Protocol Identification Number
NCT05878691
Brief Title
A Study of GRC 54276 in Participants With Advanced Solid Tumors and Lymphomas.
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.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 28, 2022 (Actual)
Primary Completion Date
July 30, 2027 (Anticipated)
Study Completion Date
July 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Glenmark Specialty S.A.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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 solid tumors and lymphomas.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Solid Tumor, Lymphoma
Keywords
Solid tumor, Lymphoma, MTD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
320 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
GRC 54276
Arm Type
Experimental
Arm Title
GRC 54276 with pembrolizumab
Arm Type
Experimental
Arm Title
GRC 54276 with atezolizumab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
GRC 54276
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
GRC 54276 + Pembrolizumab
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
GRC 54276 + Atezolizumab
Intervention Description
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.
Primary Outcome Measure Information:
Title
Dose limiting toxicities to establish the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D)
Description
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.
Time Frame
18 weeks
Title
Incidence of treatment-emergent adverse events and serious adverse events
Description
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.
Time Frame
up to 120 days
Title
Changes in the laboratory safety values from baseline to end of safety follow-up
Description
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.
Time Frame
up to 120 days
Title
Pharmacokinetic profile of GRC54276- Maximum plasma concentration (Cmax)
Description
The maximum measured plasma concentration after single or multiple dosing, tabulated by dose group and day of dosing.
Time Frame
up to 22 days
Title
Pharmacokinetic profile of GRC54276- Time to Cmax (Tmax)
Description
The time to achieve Cmax after single or multiple dosing, tabulated by dose group and day of dosing.
Time Frame
up to 22 days
Title
Pharmacokinetic profile of GRC54276- Area under the curve (AUC)
Description
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.
Time Frame
up to 22 days
Secondary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
Proportion of participants with a best response of complete response or partial response best on RECIST 1.1.
Time Frame
up to 9 months
Title
Best overall response rate
Description
Complete response, partial response, stable disease, and progressive disease, evaluated according to RECIST 1.1.
Time Frame
up to 9 months
Title
Disease control rate
Description
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.
Time Frame
up to 9 months
Title
Duration of response
Description
The time from first documentation of complete response or partial response to the first documentation of progression.
Time Frame
up to 9 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jatin Kadam
Phone
02250451200
Email
clinicaltrialsdisclosuredesk@glenmarkpharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Harsha Doddihal, MD
Organizational Affiliation
Glenmark Pharmaceuticals Ltd.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Adam Y-Beltran, MD
Organizational Affiliation
Glenmark Pharmaceuticals Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Carolina BioOncology Institute
City
Huntersville
State/Province
North Carolina
ZIP/Postal Code
28078
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John D. Powderly II, MD
Facility Name
Froedtert & Medical College of Wisconsin - Froedtert Hospital - Clinical Cancer Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226-1222
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Artemis Hospital
City
Gurgaon
State/Province
Haryana
ZIP/Postal Code
122001
Country
India
Individual Site Status
Recruiting
Facility Name
Health Care Global Enterprises Ltd (HCG)
City
Bangalore
State/Province
Karnataka
ZIP/Postal Code
5600027
Country
India
Individual Site Status
Recruiting
Facility Name
Vydehi Hospital
City
Bangalore
State/Province
Karnataka
ZIP/Postal Code
560066
Country
India
Individual Site Status
Recruiting
Facility Name
Malabar Cancer Centre
City
Kannur
State/Province
Kerala
ZIP/Postal Code
670103
Country
India
Individual Site Status
Recruiting
Facility Name
Krupamayi Hospitals
City
Aurangabad
State/Province
Maharashtra
ZIP/Postal Code
431001
Country
India
Individual Site Status
Recruiting
Facility Name
HCG Manavata Cancer Centre
City
Nashik
State/Province
Maharashtra
ZIP/Postal Code
422002
Country
India
Individual Site Status
Recruiting
Facility Name
Sankalp Hospital
City
Nashik
State/Province
Maharashtra
ZIP/Postal Code
422009
Country
India
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

A Study of GRC 54276 in Participants With Advanced Solid Tumors and Lymphomas.

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