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

NCT05878691
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Phase
Phase 1
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Recruitment status
Active, not recruiting
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Participants
320
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Lead sponsor
Glenmark Specialty S.A.
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Start date
2022-06-28
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Number of sites
18
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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.
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Short title
A Study of GRC 54276 in Participants With Advanced Solid Tumors and Lymphomas.
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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.
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Active, not recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2027-07-30
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First posted
2023-05-26
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Registry last updated
2024-07-22
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Primary completion date
2027-07-30
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Start date
2022-06-28
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Participants
320
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Participant count basis
Estimated
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Planned participants
320
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Protocol amendments
1
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Number of sites
18
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Glenmark Specialty S.A.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05878691
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ClinicalTrials.gov ID
NCT05878691
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
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  1. Dose limiting toxicities to establish the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D)

    Timeframe: 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

    Timeframe: 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

    Timeframe: 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)

    Timeframe: 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)

    Timeframe: 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)

    Timeframe: 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.

  1. Objective response rate (ORR)

    Timeframe: 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

    Timeframe: up to 9 months

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

  3. Disease control rate

    Timeframe: 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

    Timeframe: up to 9 months

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

Sources for outcomes
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Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  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.

  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.

Sources for eligibility
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  • Carolina BioOncology InstituteHuntersville, United States
  • Froedtert & Medical College of Wisconsin - Froedtert Hospital - Clinical Cancer CenterMilwaukee, United States
  • Hcg City Cancer CentreVijayawada, India
  • Mahatma Gandhi Cancer Hospital and Research InstituteVisakhapatnam, India
  • Artemis HospitalGurgaon, India
  • Health Care Global Enterprises Ltd (HCG)Bangalore, India
  • Vydehi HospitalBangalore, India
  • Cytecare Hospitals Pvt Ltd.Bengaluru, India
  • Aster CMI HospitalBengaluru, India
  • Malabar Cancer CentreKannur, India
  • Krupamayi HospitalsAurangabad, India
  • PD Hinduja Hospital and Medical Research CentreMumbai, India
  • HCG Manavata Cancer CentreNashik, India
  • Sankalp HospitalNashik, India
  • Bhaktivedanta Hospital and Research InstituteThane, India
  • AIG Hospitals, (A unit of asian Institute of Gastroenterology)Hyderabad, India
  • Basavatarakam Indo American Cancer Hospital Research InstituteHyderabad, India
  • Max Superspeciality HospitalDelhi, India
Sources for sites
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Other registry identifiers

  • CTRI/2022/05/042484
Sources for references
clinicaltrials.gov

Related records

Drugs (2)

Lead sponsors (1)

Conditions (1)

Targets (2)