APL-501 Study for Select Advanced or Relapsed/Recurrent Solid Tumors
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03053466|
Recruitment Status : Active, not recruiting
First Posted : February 15, 2017
Last Update Posted : June 6, 2019
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumor Advanced Cancers Colorectal Cancer Gastric Cancer Hepatocellular Cancer Non Small Cell Lung Cancer Renal Cancer Head and Neck Squamous Cell Carcinoma CHL Urothelial Carcinoma Gastroesophageal Junction Adenocarcinoma Microsatellite Instability Mismatch Repair Deficiency Esophageal Cancer Cancer of Unknown Primary Site Carcinosarcoma||Drug: APL-501||Phase 1|
This is a Phase 1, multicenter, 3-part study with a Dose-Escalation Segment, Cohort Extension and Dose and Disease Expansion cohorts of APL-501 injection, a humanized IgG4 monoclonal antibody, targeting the Programmed Death-1 (PD-1) membrane receptor on T lymphocytes and other cells of the immune system. Select advanced solid tumor malignancies will receive escalating doses of APL-501.
Dose escalation will occur in three subject cohorts until a protocol defined dose limited toxicity (DLT) occurs, not due to disease progression or inter-current illness, and a tentative maximum tolerated dose (MTD) or biologically effective dose (BED) is determined.
Cohort Extension will evaluate APL-501 at 3 mg/kg and 10 mg/kg on Day 1 and Day 15 every 28 days and on Day 1 every 21 days in PD-1 approved labelled indications.
At the tentative MTD, BED or recommended Phase 2 dose (RP2D), at least four tumor types in the Dose and Disease Expansion will be assessed at a equivalent non-weight based dose to further evaluate toxicity and preliminary efficacy.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||114 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Masking Description:||Open Label|
|Official Title:||A Phase 1 Multicenter, Dose Escalation, Cohort Extension and Dose and Disease Expansion Study of APL-501 in Subjects With Select Advanced or Relapsed/Recurrent Solid Tumors|
|Actual Study Start Date :||March 27, 2017|
|Estimated Primary Completion Date :||February 2020|
|Estimated Study Completion Date :||December 2021|
Subjects will be assigned to a dose level in the order of study entry. Treatment includes a minimum of four 28-day cycles at three planned dose levels (1, 3, and 10 mg/kg). In the Dose Escalation Segment, each treatment cycle is comprised of 2 doses of study drug administered on Days 1 and 15 of a 28-day cycle. In the Cohort Extension, the treatment cycle will consist of 2 doses of study drug administered on Days 1 and 15 of a 28-day cycle and 1 dose of study drug administered on Day 1 of a 21-day cycle.
In Dose and Disease Expansion, the treatment cycle will consist of 2 doses of study drug (non-weight based dosing of 400 mg) administered on Days 1 and 15 of a 28-day cycle.
Other Name: GB226
- Number of participants with treatment related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE v4.03) in patients with advance solid tumors [ Time Frame: From the time of informed consent from signature until Day 28 after Cycle 1; Dose Escalation - Approximately 9 months ]Adverse events, serious adverse events, dose limiting toxicities according to the National Cancer Institute (NCI) Terminology Criteria for Adverse Events (CTCAE v4.03)
- Determine the recommended Phase 2 dose and schedule [ Time Frame: An average of 1 year ]adverse events, serious adverse events, dose limiting toxicities
- Area under the plasma concentration versus time curve (AUC) [ Time Frame: Up to 4 months (1 cycle = 28 days) ]AUC, 0-infinity
- Maximum plasma concentration [ Time Frame: Up to 4 months (1 cycle = 28 days) ]Cmax
- Time to reach Cmax [ Time Frame: Up to 4 months (1 cycle = 28 days) ]Tmax
- Objective Response Rate (ORR) [ Time Frame: Approximately 24 months ]The treatment effect of APL-501 will be assessed by RECIST v1.1 and by irRECIST to determine proportion of patients with complete response or partial response.
- Duration of Response (DOR) [ Time Frame: Approximately 24 months ]The treatment effect of APL-501 will be assessed by RECIST v1.1 or by irRECIST to determine duration of response. Time from first documented complete response or partial response until subsequent documented disease progression or death.
- Time to Response (TTR) [ Time Frame: Approximately 24 months ]The treatment effect of APL-501 will be assessed by RECIST v1.1 and by irRECIST to determine time to complete response and partial response.
- Disease Control Rate (DCR) [ Time Frame: Approximately 24 months ]The treatment effect of APL-501 will be assessed by RECIST v1.1 and irRECIST to determine disease control rate. Proportion of patients with best overall response of complete response, partial response, or stable disease.
- Progression Free Survival [ Time Frame: Approximately 24 months ]The effect of APL-501 will be assessed by RECIST v1.1 and per irRECIST to determine progression free survival as time from date of first dose to date of disease progression or death.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03053466
|Australia, New South Wales|
|Chris O'Brien Lifehouse|
|Camperdown, New South Wales, Australia, 2050|
|The Tweed Hospital|
|Tweed Heads, New South Wales, Australia, 2485|
|Australia, New South Whales|
|St. Vincent's Hospital, The Kinghorn Cancer Center|
|Darlinghurst, New South Whales, Australia, 2010|
|Cabrini Education and Research Precinct|
|Malvern, Victoria, Australia, 3144|
|Peter MaCallum Cancer Centre|
|Melbourne, Victoria, Australia, 3000|
|Melbourne, Victoria, Australia, 3004|
|Australia, Western Australia|
|Linear Clinical Research|
|Nedlands, Western Australia, Australia, 6009|
|Study Chair:||Fabio Benedetti, MD||Chief Medical Officer|