Clinical trial NCT05878691: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lymphoma
Keywords: Solid tumor
Lymphoma
MTD
Lead sponsor: Glenmark Specialty S.A.
Sponsor class: INDUSTRY
First posted: 2023-05-26
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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).
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.

Primary outcomes:
measure: Dose limiting toxicities to establish the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D)
timeFrame: 18 weeks
measure: Incidence of treatment-emergent adverse events and serious adverse events
timeFrame: up to 120 days
measure: Changes in the laboratory safety values from baseline to end of safety follow-up
timeFrame: up to 120 days
measure: Pharmacokinetic profile of GRC54276- Maximum plasma concentration (Cmax)
timeFrame: up to 22 days
measure: Pharmacokinetic profile of GRC54276- Time to Cmax (Tmax)
timeFrame: up to 22 days
measure: Pharmacokinetic profile of GRC54276- Area under the curve (AUC)
timeFrame: up to 22 days
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: up to 9 months
measure: Best overall response rate
timeFrame: up to 9 months
measure: Disease control rate
timeFrame: up to 9 months
measure: Duration of response
timeFrame: up to 9 months
Other outcomes:
Locations:
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Milwaukee
country: United States
facility: Froedtert & Medical College of Wisconsin - Froedtert Hospital - Clinical Cancer Center
state: Wisconsin
city: Vijayawada
country: India
facility: Hcg City Cancer Centre
state: Andhra Pradesh
city: Visakhapatnam
country: India
facility: Mahatma Gandhi Cancer Hospital and Research Institute
state: Andhra Pradesh
city: Gurgaon
country: India
facility: Artemis Hospital
state: Haryana
city: Bangalore
country: India
facility: Health Care Global Enterprises Ltd (HCG)
state: Karnataka
city: Bangalore
country: India
facility: Vydehi Hospital
state: Karnataka
city: Bengaluru
country: India
facility: Cytecare Hospitals Pvt Ltd.
state: Karnataka
city: Bengaluru
country: India
facility: Aster CMI Hospital
state: Karnataka
city: Kannur
country: India
facility: Malabar Cancer Centre
state: Kerala
city: Aurangabad
country: India
facility: Krupamayi Hospitals
state: Maharashtra
city: Mumbai
country: India
facility: PD Hinduja Hospital and Medical Research Centre
state: Maharashtra
city: Nashik
country: India
facility: HCG Manavata Cancer Centre
state: Maharashtra
city: Nashik
country: India
facility: Sankalp Hospital
state: Maharashtra
city: Thāne
country: India
facility: Bhaktivedanta Hospital and Research Institute
state: Maharashtra
city: Hyderabad
country: India
facility: AIG Hospitals, (A unit of asian Institute of Gastroenterology)
state: Telangana
city: Hyderabad
country: India
facility: Basavatarakam Indo American Cancer Hospital Research Institute
state: Telangana
city: Delhi
country: India
facility: Max Superspeciality Hospital
Study officials:
affiliation: Glenmark Pharmaceuticals Ltd.
name: Veena Gupta
role: STUDY_DIRECTOR
References: