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

• Sponsor: Glenmark Specialty S.A. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05878691
• Collaborator: (none)
• Enrollment: 320
• Locations: 8
• Arms: 3
• Anticipated Duration (Months): 61
• Patients Per Site: 40
• Patients Per Site Per Month: 0.7

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumor; Lymphoma	Drug: GRC 54276; Drug: GRC 54276 + Pembrolizumab; Drug: GRC 54276 + Atezolizumab	Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 320 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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.
• Actual Study Start Date: Jun 28, 2022
• Anticipated Primary Completion Date: Jul 30, 2027
• Anticipated Study Completion Date: Jul 30, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GRC 54276	Drug: 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.
Experimental: GRC 54276 with pembrolizumab	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.
Experimental: GRC 54276 with atezolizumab	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.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

Secondary Outcome Measures

1. 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.

2. Best overall response rate [up to 9 months]

   Complete response, partial response, stable disease, and progressive disease, evaluated according to RECIST 1.1.

3. 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.

4. Duration of response [up to 9 months]

   The time from first documentation of complete response or partial response to the first documentation of progression.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

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

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

7. 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)

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

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Froedtert & Medical College of Wisconsin - Froedtert Hospital - Clinical Cancer Center	Milwaukee	Wisconsin	United States	53226-1222
2	Artemis Hospital	Gurgaon	Haryana	India	122001
3	Health Care Global Enterprises Ltd (HCG)	Bangalore	Karnataka	India	5600027
4	Vydehi Hospital	Bangalore	Karnataka	India	560066
5	Malabar Cancer Centre	Kannur	Kerala	India	670103
6	Krupamayi Hospitals	Aurangabad	Maharashtra	India	431001
7	HCG Manavata Cancer Centre	Nashik	Maharashtra	India	422002
8	Sankalp Hospital	Nashik	Maharashtra	India	422009

Sponsors and Collaborators

• Glenmark Specialty S.A.

Investigators

• Study Director: Harsha Doddihal, MD, Glenmark Pharmaceuticals Ltd.
• Study Director: Adam Y-Beltran, MD, Glenmark Pharmaceuticals Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Glenmark Specialty S.A.
• ClinicalTrials.gov Identifier: NCT05878691
• Other Study ID Numbers: GRC 54276-101; CTRI/2022/05/042484
• First Posted: May 26, 2023
• Last Update Posted: May 30, 2023
• Last Verified: May 1, 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Glenmark Specialty S.A.: Solid tumor; Lymphoma; MTD
• Additional relevant MeSH terms: Lymphoma; Pembrolizumab; Atezolizumab

Study Results

No Results Posted as of May 30, 2023