APL-501 Study for Select Advanced or Relapsed/Recurrent Solid Tumors

Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03053466
• Other study ID #: APL-501-01
• Status: Completed
• Phase: Phase 1
• Start date: March 27, 2017
• Est. completion date: February 25, 2022

Study information

• Verified date: May 2022
• Source: Apollomics (Australia) Pty. Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the safety, tolerability, and recommended dose schedule of APL-501 in individuals with advanced or relapsed or recurrent solid tumors.

Description:

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.

At the tentative MTD, BED or recommended Phase 2 dose (RP2D), at least two tumor types in the Dose and Disease Expansion will be assessed at an equivalent non-weight based dose to further evaluate toxicity and preliminary efficacy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: February 25, 2022
• Est. primary completion date: February 25, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Major Inclusion Criteria:

• Able to understand and comply with study procedures, understand the risks involved, and provide written informed consent.

Dose Escalation:

• Histologically and / or cytological confirmed solid tumors: colorectal, endometrial, gastric including, gastroesophageal junction adenocarcinoma (GC), head and neck (esophageal, hepatocellular (HCC), non-small cell lung cancer, mesothelioma, ovarian, and renal cell carcinoma (RCC), either refractory or relapsed to standard therapy or for which no effective standard therapy is available.

• No restriction to number of prior therapies for Dose Escalation Segment except for gastric and renal cell carcinoma.

Cohort Extension:

• Histologically and/or cytological confirmed solid tumors with an approved labelled indication for PD-1 inhibitors.

• Tumor biopsy at study entry and during therapy. Tumor sites used to satisfy this criterion must not have received any prior radiation therapy. Sites for biopsy must be distinct from target lesions used for efficacy assessment.

• Measurable disease according to RECIST v1.1.

Dose and Disease Expansion:

• MSI-H or dMMR per local laboratory and failed at least one prior line of standard of care chemotherapy per local standards.

• Carcinoma of Unknown Primary

Major Exclusion Criteria:

• History of severe hypersensitivity to mAbs, excipients of the drug product or other components

• Prior malignancy active within the previous 2 years except for locally curable cancers that have been cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast

• Any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy

• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PDL-2, or anti-CTLA-4 antibody (or any other antibody targeting T cell co-stimulation pathways) (except NSCLC)

• Known significant mental illness or other conditions such as active alcohol or other substance abuse that, in the opinion of the Investigator, predisposes the subject to high risk of noncompliance with the protocol treatment or assessments.

Related Conditions & MeSH terms

• Cancer of Unknown Primary Site
• Microsatellite Instability
• Mismatch Repair Deficiency
• Neoplasms
• Neoplasms, Unknown Primary
• Solid Tumor

Intervention

Drug:
• APL-501
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. 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.

Locations

Country	Name	City	State
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Cabrini Health Limited	Malvern	Victoria
Australia	Nucleus Network	Melbourne	Victoria
Australia	Peter MaCallum Cancer Centre	Melbourne	Victoria
Australia	Linear Clinical Research	Nedlands	Western Australia

Sponsors (3)

Lead Sponsor	Collaborator
Apollomics (Australia) Pty. Ltd.	Apollomics Inc. (formerly CBT Pharmaceuticals, Inc.), Novotech (Australia) Pty Limited

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Adverse events, serious adverse events, dose limiting toxicities according to the National Cancer Institute (NCI) Terminology Criteria for Adverse Events (CTCAE v4.03)	From the time of informed consent from signature until Day 28 after Cycle 1; Dose Escalation - Approximately 9 months
Secondary	Determine the recommended Phase 2 dose and schedule	adverse events, serious adverse events, dose limiting toxicities	An average of 1 year
Secondary	Area under the plasma concentration versus time curve (AUC)	AUC, 0-infinity	Up to 4 months (1 cycle = 28 days)
Secondary	Maximum plasma concentration	Cmax	Up to 4 months (1 cycle = 28 days)
Secondary	Time to reach Cmax	Tmax	Up to 4 months (1 cycle = 28 days)
Secondary	Objective Response Rate (ORR)	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.	Approximately 24 months
Secondary	Duration of Response (DOR)	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.	Approximately 24 months
Secondary	Time to Response (TTR)	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.	Approximately 24 months
Secondary	Disease Control Rate (DCR)	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.	Approximately 24 months
Secondary	Progression Free Survival	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.	Approximately 24 months

External Links

•   Company website for Apollomics Inc.