A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor

NCT04964375 | Unknown Phase 1

• 1 other identifier: ABSK043-101
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

This is a Phase 1, Open-Label Study of ABSK043 to Assess Safety, Tolerability, and Pharmacokinetics in Patients with Advanced Solid Tumor. Preliminary antitumor activity will also be assessed. Investigate the pharmacodynamics (PD) effects and Investigate the metabolites of oral ABSK043

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (2)

• DLT

  dose-limiting toxicity

  At the end of Cycle 1 (each cycle is 28 days)

• Incidence and Severity of AEs

  Adverse events (AEs), adverse events of special interest (AESIs) and serious adverse events (SAEs)

  Through study completion, an average of 6 months

Secondary Outcomes (14)

• PFS

  throughout study completion, on average of half year

• DCR

  throughout study completion, on average of half year

• DOR

  throughout study completion, on average of half year

• Cmax

  at the end of Cycle 1 Day15 (each cycle is 28 days)

• Tmax

  at the end of Cycle 1 Day15 (each cycle is 28 days)

Other Outcomes (3)

• surface PD-L1 expression

  Time Frame:at the end of Cycle 1 Day15 (each cycle is 28 days)

• metabolites of ABSK043

  Time Frame: at the end of Cycle 1 Day15 (each cycle is 28 days)

• soluble PD-L1,

  Time Frame:at the end of Cycle 1 Day15 (each cycle is 28 days)

Study Arms (1)

ABSK043

EXPERIMENTAL

Dose escalation of oral ABSK043 with a starting dose of 200mg once daily will be guided by"BOIN" escalation rules based on safety data until an MTD has been identified or a RDE. For each dose,In the escalation part, sequential cohorts of patients will receive an oral dose of ABSK043 in repeated 28-day cycles. Starting dose level will be 200 mg QD. Cohort 3 on 800mg will be switched to 400mg BID.Then, patients will continuously receive ABSK043 （total daily dose） in repeated 28-day cycles.For the Dose Expansion Phase, patients will each receive orally administered doses of ABSK043 at the RDE in repeated 28-day cycles.

Drug: ABSK043 oral capsule

Interventions

ABSK043 oral capsule DRUG

ABSK043 is a novel, oral small molecule inhibitor of PD-L1

ABSK043

Eligibility Criteria

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

You may qualify if:

• Patient should understand, sign, and date the written voluntary informed consent form prior to screening.
• Male or female aged 18 years or older (or other age range required by local regulations or IRB).
• For Escalation part: patients must have histologically confirmed solid tumors that have progressed on or intolerance to standard therapy or whom no standard therapy exists or whom refuse to receive standard therapy；
• For Expansion Part:
• Melanoma cohort: Patients must have histologically confirmed melanoma that have have progressed on or intolerance to standard therapy(including immune-checkpoint inhibitors) or whom no standard therapy exists or whom refuses to receive standard therapy
• MSI-H/dMMR cohort: Patients must have histologically confirmed solid tumors harboring MSI-H or dMMR that have progressed on or intolerance to standard therapy or whom no standard therapy exists or whom refuses to receive standard therapy.
• Patients must have at least one measurable target lesion according to RECIST 1.1.
• Patients are willing to receive biopsy. 4. ECOG performance status 0 or 1 5. Life expectancy ≥3 months 6. Adequate organ function and bone marrow function as indicated by the following screening assessments performed within 14 days prior to the first dose of study drug:
• Absolute neutrophil count (ANC) ≥1.5×109/L
• Platelet count (PLT) ≥75×109/L without transfusions within 14 days before 1st dose
• Hemoglobin (Hb) ≥90 g/L
• Total bilirubin (TBIL) ≤1.5×ULN
• Aspartate transaminase (AST)/alanine transaminase (ALT), ≤3×ULN (≤5 × ULN in the presence of hepatic metastases).
• Serum creatinine (Cr) of ≤1.5×ULN for the reference laboratory or creatinine clearance (Crcl) ≥50 mL/min based either on urine collection or Cockcroft-Gault estimation

You may not qualify if:

• Known allergy or hypersensitivity to any component of the investigational product.
• For expansion part MSI-H or dMMR cohort only: previously treated with PD-(L)1 pathway inhibitors (including monoclonal antibody and small molecular agents).
• History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis, etc.
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan, history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• For expansion part only: Has a known additional malignancy that is progressing or required active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or other in situ cancers.
• Inability to take oral medication or significant nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption of oral medication.
• Previous anti-cancer therapy, including chemotherapy (chemotherapy with nitrosourea or mitomycin should be 6 weeks prior to initiation of study treatment), radiotherapy, molecular targeted therapy or other investigational drugs received in previous clinical trial ≤4 weeks; endocrine therapy ≤2 weeks or ≤5-half-life (whichever is shorter) prior to initiation of study treatment.
• Major surgery within 4 weeks of the first dose of study drug and all surgical wounds must be healed and free of infection or dehiscence.
• Vaccination with a live, attenuated vaccine within 4 weeks of the first dose of study treatment and while on trial is prohibited except for administration of inactivate vaccines (e.g., COVID-19 vaccines, inactivated influenza vaccines).
• Prior toxicities from chemotherapy, radiotherapy, and other anti-cancer therapies, including immunotherapy that have not regressed to Grade ≤1 severity (CTCAE v5.0) with the exception of alopecia, vitiligo or event(s) that is considered non-clinical meaningful by the Investigator.
• History of Grade ≥3 immune-related adverse event(s) occurred in previous treatment.
• Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to randomization, or anticipated requirement for systemic immunosuppressive medications during the trial (patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study; patients with a history of allergic reaction to IV contrast requiring steroid pre-treatment should have baseline and subsequent tumor assessments performed using MRI; the use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.
• For expansion part only: last treatment with therapeutic oral or intravenous antibiotics within 2 weeks prior to first dose of study treatment.
• Concomitant use of the drugs/remedies that may cause pharmacokinetic drug-drug interactions; Consumption of grapefruit juice, grapefruit hybrids, pomegranates, starfruit, pomelos, Seville oranges or juice or products within 7 days prior to the first dose of study medication (for Escalation Part only).
• Active central nervous system (CNS) metastases including cerebral edema, system hormone treatment, disease progression due to intracranial lesions, leptomeningeal metastasis, and other clinical symptoms related to CNS metastases (if stable disease\>8 weeks after treatment and free from glucocorticoids can be enrolled).

Sponsors & Collaborators

• Abbisko Therapeutics Co, Ltd: lead

Study Sites (3)

Icon Cancer Centre South Brisbane

Brisbane, Queensland, 4101, Australia

RECRUITING

Peninsula & South Eastern Haematology and Oncology Group

Frankston, Victoria, Australia

RECRUITING

Sydney South West Private Hospital

Liverpool, Australia

RECRUITING

MeSH Terms

Conditions

Neoplasms

Study Officials

• Jermaine Coward

  Icon Cancer Centre South Brisbane

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ming Zhang

CONTACT

+86-21-68912098; ming.zhang@abbisko.com

Brendan Kirwan

CONTACT

+ 61 290168100; brendan.kirwan@iqvia.com

Study Design

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

Study Record Dates

• First Submitted: June 24, 2021
• First Posted: July 16, 2021
• Study Start: August 31, 2021
• Primary Completion: October 23, 2022
• Study Completion: March 23, 2023
• Last Updated: April 27, 2022

Record last verified: 2021-07

Locations

AU (3)