Dose-escalation Study of APG-1387 and Toripalimab in Solid Tumors

NCT04284488 | Terminated Phase 1

• 1 other identifier: APG1387XC101
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

Brief Summary

An ascending dose study in patients with solid tumors to evaluate the safety, tolerability, pharmacodynamics and efficacy of APG-1387 in combination with toripalimab. A phase II study of 3 cohorts will be included.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Recommended Phase 2 dose(RP2D) (Applicable for: phase I stage in various solid tumor types).

  Recommended phase 2 dose(RP2D) of APG-1387 in combination with toripalimab in subjects with solid tumors.

  21 days.

• Disease control rate (Applicable for: phase II in cohorts of Colorectal Cancer, Nasopharyngeal Carcinoma and Non-Small Cell Lung Cancer) .

  Evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) Version1.1 and iRECIST.

  18-24months.

Secondary Outcomes (2)

• Overall Response (Applicable for: phase I stage in various solid tumor types)

  18-24months.

• Incidence of Treatment-Emergent Adverse Events (safety and tolerability) (Applicable for: phase II)

  18-24months.

Study Arms (1)

APG-1387 in combination with Toripalimab

EXPERIMENTAL

Drug: APG-1387 for Injection; Drug: Toripalimab

Interventions

APG-1387 for Injection DRUG

APG-1387 IV on Days 1 and 8 of each 21-Day Cycle. The following doses of APG-1387 to be studied: 20, 30, and 45mg. In the phase II, the assigned recommended phase two dose will be administered in all cohorts.

APG-1387 in combination with Toripalimab

Toripalimab DRUG

240 mg toripalimab IV on Day 1 of each 21-Day Cycle

Also known as: JS001

APG-1387 in combination with Toripalimab

Eligibility Criteria

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

You may qualify if:

• Histopathologically confirmed advanced solid tumors
• For phase II CRC group only: Patients with histologically confirmed microsatellite stable (detected by immunohistochemistry, PCR or NGS methods) advanced colorectal cancer.
• For phase II NPC group only: Patients with histologically or cytologically confirmed advanced NPC.
• For phase II NSCLC group only: Patients with histologically confirmed or cytologically confirmed advanced non-small cell lung cancer together with wild-type EGFR/ALK/ROS1 (first or second-generation sequencing results are allowed).
• Patients who have failed standard antitumor therapy.
• At least one evaluable lesion according to RECIST 1.1 criteria.
• Age greater than 18 years, both men and women.
• ECOG: 0 to 1.
• Expected survival ≥ 3 months.
• The function of vital organs meets the following criteria (no blood components and cell growth factors are allowed 2 weeks before the start of study treatment):
• Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L;
• Platelets ≥ 100 × 10\^9/L;
• Hemoglobin ≥ 90 g/L;
• Serum albumin ≥ 30 g/L;
• Total bilirubin ≤ 1.5 x the upper limit of normal(ULN), ALT and AST ≤ 2.5 x ULN; if there is liver metastasis, ALT and AST ≤ 5 x ULN;

You may not qualify if:

• Cytotoxic chemotherapy, radiation therapy, surgery (except minor surgery), anticancer therapy with hormone therapy (except hormone for hypothyroidism or estrogen replacement therapy (ERT)), or any clinical study treatment within 28 days prior to the first dose of study drug; or clinically significant tumor embolism or tumor lysis syndrome (TLS).
• Immunotherapy, biologic therapy or anti-TNFa therapy within 28 days or 5 half-lives (whichever is shorter) prior to receiving the first dose of study drug.
• Patients who have received targeted therapy within 28 days prior to first dose of study drug.
• Prior treatment with anti PD-1, anti PD-L1, or anti PD-L2 agents (Phase II CRC cohort only).
• Patients have an immunodeficiency diagnosis or are receiving chronic systemic steroid therapy (daily dose of more than 10 mg prednisone equivalent) or any form of immunosuppressive therapy 7 days prior to the first dose of trial treatment.
• Patients have any active autoimmune disease or a history of autoimmune disease (such as interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, decreased thyroid function (can be included if hormone replacement therapy is effective); patients with vitiligo or asthma that has been completely relieved in childhood and does not require any intervention after adulthood can be included, and patients with asthma requiring bronchodilators for medical intervention cannot be included.
• Patient has an active infection or unexplained fever \> 38.5。C within 2 weeks prior to the first dose (subjects may be enrolled due to tumor generated fever as judged by the investigator).
• Any evidence of a past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroids, or clinically active interstitial lung disease.
• Hepatic decompensation.
• Evidence of any severe or uncontrolled systemic disease; various chronic active infections such as hepatitis B (evidence of hepatitis activity such as HBV-DNA ≥ 104 copies/mL or 2000 IU/mL), hepatitis C, and HIV.
• Any of the following cardiac criteria: Mean QTc\> 470 msec at rest during screening; Any clinically important abnormality in rhythm, conduction, or morphology of the resting electrocardiogram (ECG) (e.g., complete left bundle branch block, third degree heart block, second degree heart block); Congenital long QT syndrome or family history of long QT syndrome.
• Uncontrolled hypertension (requiring 2 or more medications to control blood pressure); Unstable cardiac pain; Angina pectoris within 3 months of study entry; Congestive heart failure (NYHA class II or higher); Previous myocardial infarction (NSTEMI or STEMI) within 6 months of study entry; Serious cardiac arrhythmia requiring medical attention; Serious hepatic, renal, gastrointestinal, or metabolic disease.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to APG-1387 or toripalimab or their constituents.
• Have received a live vaccine within 28 days prior to the first dose of investigational product. Live vaccines include but are not limited to the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacille Calmette-Guérin vaccine (BCG) and typhoid. Injectable seasonal influenza vaccines are usually inactivated viral vaccines and are therefore allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed.
• Patients who have not sufficiently recovered after surgical treatment as judged by the investigator. Patients with major surgery within 28 days prior to the first dose of study drug and minor surgery within 7 days prior to the start of the study.

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead

Study Sites (3)

Foshan First People's Hospital

Foshan, Guangdong, China

Location

Sun-Yat Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

The Affiliated Hospital OF Guangxi Medical University

Nanning, Guangxi, 530021, China

Location

MeSH Terms

Interventions

APG-1387; Injections; toripalimab

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Yifan Zhai, M.D., Ph.D.

  Ascentage Pharma Group Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: February 5, 2020
• First Posted: February 25, 2020
• Study Start: April 10, 2020
• Primary Completion: November 30, 2024
• Study Completion: November 30, 2024
• Last Updated: January 8, 2026

Record last verified: 2026-01

Locations

CN (3)