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

NCT ID: NCT05878691

Last Updated: 2024-07-22

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 320 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-28
• Study Completion Date: 2027-07-30

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.

Conditions

Advanced Solid Tumor; Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GRC 54276

Group Type: EXPERIMENTAL

GRC 54276

Intervention Type: DRUG

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 with pembrolizumab

Group Type: EXPERIMENTAL

GRC 54276 + Pembrolizumab

Intervention Type: DRUG

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 with atezolizumab

Group Type: EXPERIMENTAL

GRC 54276 + Atezolizumab

Intervention Type: DRUG

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.

Interventions

GRC 54276

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

GRC 54276 + Pembrolizumab

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

GRC 54276 + Atezolizumab

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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.

2. 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.

3. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1 measured within 72 hours of treatment.

4. Predicted life expectancy of ≥3 months.

5. 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).

6. Adequate renal function as indicated by creatinine clearance of ≥60mL/min calculated using Cokroft-Gault method.

7. Adequate cardiac function, left ventricular ejection fraction (LVEF) of ≥50% as assessed by multi-gated acquisition (MUGA) or ultrasound/echocardiography (ECHO).

Exclusion Criteria

1. 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.

2. 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)

3. 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)

4. 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:

1. Adrenal replacement steroid (dose ≤10 mg daily of prednisone or equivalent)

2. Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption

3. 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)

5. Pregnant/planning to be pregnant or breast-feeding women.

6. Any important medical illness or abnormal laboratory finding that would increase the risk of participating in this study (based on the investigator's judgment).

7. Any known severe allergic reaction to pembrolizumab/atezolizumab or its excipients.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Glenmark Specialty S.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Veena Gupta

Role: STUDY_DIRECTOR

Glenmark Pharmaceuticals Ltd.

Locations

Carolina BioOncology Institute

Huntersville, North Carolina, United States

Froedtert & Medical College of Wisconsin - Froedtert Hospital - Clinical Cancer Center

Milwaukee, Wisconsin, United States

Hcg City Cancer Centre

Vijayawada, Andhra Pradesh, India

Mahatma Gandhi Cancer Hospital and Research Institute

Visakhapatnam, Andhra Pradesh, India

Artemis Hospital

Gurgaon, Haryana, India

Health Care Global Enterprises Ltd (HCG)

Bangalore, Karnataka, India

Vydehi Hospital

Bangalore, Karnataka, India

Cytecare Hospitals Pvt Ltd.

Bengaluru, Karnataka, India

Aster CMI Hospital

Bengaluru, Karnataka, India

Malabar Cancer Centre

Kannur, Kerala, India

Krupamayi Hospitals

Aurangabad, Maharashtra, India

PD Hinduja Hospital and Medical Research Centre

Mumbai, Maharashtra, India

HCG Manavata Cancer Centre

Nashik, Maharashtra, India

Sankalp Hospital

Nashik, Maharashtra, India

Bhaktivedanta Hospital and Research Institute

Thāne, Maharashtra, India

AIG Hospitals, (A unit of asian Institute of Gastroenterology)

Hyderabad, Telangana, India

Basavatarakam Indo American Cancer Hospital Research Institute

Hyderabad, Telangana, India

Max Superspeciality Hospital

Delhi, , India

Countries

United States; India

Other Identifiers

CTRI/2022/05/042484

Identifier Type: REGISTRY

Identifier Source: secondary_id

GRC 54276-101

Identifier Type: -

Identifier Source: org_study_id