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

NCT05878691 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: GRC 54276-101CTRI/2022/05/042484
• Study Type: interventional
• Target: 320
• Locations: 2 countries
• Sites: 18

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

Keywords

Solid tumor; Lymphoma; MTD

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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.

  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.

  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.

  up to 22 days

Secondary Outcomes (4)

• Objective response rate (ORR)

  up to 9 months

• Best overall response rate

  up to 9 months

• Disease control rate

  up to 9 months

• Duration of response

  up to 9 months

Study Arms (3)

GRC 54276

EXPERIMENTAL

Drug: GRC 54276

GRC 54276 with pembrolizumab

EXPERIMENTAL

Drug: GRC 54276 + Pembrolizumab

GRC 54276 with atezolizumab

EXPERIMENTAL

Drug: GRC 54276 + Atezolizumab

Interventions

GRC 54276 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

GRC 54276 + Pembrolizumab 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 pembrolizumab

GRC 54276 + Atezolizumab 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.

GRC 54276 with atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Glenmark Specialty S.A.: lead

Study Sites (18)

Carolina BioOncology Institute

Huntersville, North Carolina, 28078, United States

Location

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

Milwaukee, Wisconsin, 53226-1222, United States

Location

Hcg City Cancer Centre

Vijayawada, Andhra Pradesh, 520002, India

Location

Mahatma Gandhi Cancer Hospital and Research Institute

Visakhapatnam, Andhra Pradesh, 530017, India

Location

Artemis Hospital

Gurgaon, Haryana, 122001, India

Location

Health Care Global Enterprises Ltd (HCG)

Bangalore, Karnataka, 5600027, India

Location

Vydehi Hospital

Bangalore, Karnataka, 560066, India

Location

Cytecare Hospitals Pvt Ltd.

Bengaluru, Karnataka, 560064, India

Location

Aster CMI Hospital

Bengaluru, Karnataka, 560092, India

Location

Malabar Cancer Centre

Kannur, Kerala, 670103, India

Location

Krupamayi Hospitals

Aurangabad, Maharashtra, 431001, India

Location

PD Hinduja Hospital and Medical Research Centre

Mumbai, Maharashtra, 400052, India

Location

HCG Manavata Cancer Centre

Nashik, Maharashtra, 422002, India

Location

Sankalp Hospital

Nashik, Maharashtra, 422009, India

Location

Bhaktivedanta Hospital and Research Institute

Thane, Maharashtra, 401107, India

Location

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

Hyderabad, Telangana, 500032, India

Location

Basavatarakam Indo American Cancer Hospital Research Institute

Hyderabad, Telangana, 500034, India

Location

Max Superspeciality Hospital

Delhi, 110017, India

Location

MeSH Terms

Conditions

Lymphoma

Interventions

pembrolizumab; atezolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Veena Gupta

  Glenmark Pharmaceuticals Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2023
• First Posted: May 26, 2023
• Study Start: June 28, 2022
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 30, 2027
• Last Updated: July 22, 2024

Record last verified: 2024-07

Locations

US (2); IN (16)