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

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

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.

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.

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.