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

Phase 1

Active, not recruiting

• Conditions: Advanced Solid Tumor; Lymphoma
• Interventions: Drug: GRC 54276 + Atezolizumab; Drug: GRC 54276 + Pembrolizumab; Drug: GRC 54276

• Registration Number: NCT05878691
• Lead Sponsor: Glenmark Specialty S.A.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-06-28
• Study First Submitted: 2023-05-19
• Study First Submitted QC: 2023-05-19
• Study First Posted: 2023-05-26
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-19
• Last Update Posted: 2024-07-22
• Primary Completion: 2027-07-30
• Study Completion: 2027-07-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 320

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).
8. For Part 2, dose expansion cohorts inclusion criteria specific to tumor types will be updated after completion of Part 1.

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
GRC 54276 with atezolizumab	GRC 54276 + Atezolizumab	-
GRC 54276 with pembrolizumab	GRC 54276 + Pembrolizumab	-
GRC 54276	GRC 54276	-

Primary Outcome Measures

Name	Time	Method
Incidence of treatment-emergent adverse events and serious adverse events	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	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)	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- Area under the curve (AUC)	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.
Dose limiting toxicities to establish the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D)	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.
Pharmacokinetic profile of GRC54276- Time to Cmax (Tmax)	up to 22 days	The time to achieve Cmax after single or multiple dosing, tabulated by dose group and day of dosing.

Secondary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	up to 9 months	Proportion of participants with a best response of complete response or partial response best on RECIST 1.1.
Disease control rate	up to 9 months	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	up to 9 months	The time from first documentation of complete response or partial response to the first documentation of progression.
Best overall response rate	up to 9 months	Complete response, partial response, stable disease, and progressive disease, evaluated according to RECIST 1.1.

Trial Locations

Locations (18)

Basavatarakam Indo American Cancer Hospital Research Institute; 🇮🇳 Hyderabad, Telangana, India

Carolina BioOncology Institute; 🇺🇸 Huntersville, North Carolina, United States

Froedtert & Medical College of Wisconsin - Froedtert Hospital - Clinical Cancer Center; 🇺🇸 Milwaukee, Wisconsin, United States

HCG Manavata Cancer Centre; 🇮🇳 Nashik, Maharashtra, India

Health Care Global Enterprises Ltd (HCG); 🇮🇳 Bangalore, Karnataka, India

Malabar Cancer Centre; 🇮🇳 Kannur, Kerala, India

Sankalp Hospital; 🇮🇳 Nashik, Maharashtra, India

Bhaktivedanta Hospital and Research Institute; 🇮🇳 Thāne, Maharashtra, India

Cytecare Hospitals Pvt Ltd.; 🇮🇳 Bengaluru, Karnataka, India

Hcg City Cancer Centre; 🇮🇳 Vijayawada, Andhra Pradesh, India

Aster CMI Hospital; 🇮🇳 Bengaluru, Karnataka, India

Vydehi Hospital; 🇮🇳 Bangalore, Karnataka, India

Max Superspeciality Hospital; 🇮🇳 Delhi, India

Mahatma Gandhi Cancer Hospital and Research Institute; 🇮🇳 Visakhapatnam, Andhra Pradesh, India

Artemis Hospital; 🇮🇳 Gurgaon, Haryana, India

Krupamayi Hospitals; 🇮🇳 Aurangabad, Maharashtra, India

PD Hinduja Hospital and Medical Research Centre; 🇮🇳 Mumbai, Maharashtra, India

AIG Hospitals, (A unit of asian Institute of Gastroenterology); 🇮🇳 Hyderabad, Telangana, India