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

STATUS

Recruiting
participants needed

108
sponsor

Ascentage Pharma Group Inc.

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Updated on 19 February 2024

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cancer

metastasis

solid tumour

neutrophil count

lung cancer

antineoplastic

growth factor

liver metastasis

immunohistochemistry

alopecia

neuropathy

toripalimab

brain metastasis

colorectal cancer

hair thinning

non-small cell lung cancer

EGFR

small cell lung cancer

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.

Description

This study will be conducted in two phases. In phase Ib, the safety and efficacy of different dose levels of APG-1387 in combination with 240 mg toripalimab will be explored to determine the recommended Phase 2 dose (RP2D) of APG-1387 in combination therapy, both administered as a 30-minute intravenous (IV) infusion. The following proposed doses of APG-1387 are to be evaluated: 20,30, or 12mg (in case no DLT occur in high dose levels, 12mg may be initiated for further exploration to determine RP2D comprehensively.) The Phase II portion, will compromise 3 cohorts of 29-31 patients.

The 3 cohorts will include the following:

Colorectal cancer
Nasopharyngeal carcinoma
Non-small cell lung cancer A Simon's 2-stage design will be used for each of the cohorts in colorectal cancer, nasopharyngeal carcinoma and non-small cell lung cancer. A predefined analysis will be performed in the first stage, and failure to achieve the prespecified efficacy will halt enrollment to avoid futile treatment.

Details

Condition	Advanced Solid Tumor
Age	18-100 years
Treatment	Toripalimab, APG-1387 for Injection
Clinical Study Identifier	NCT04284488
Sponsor	Ascentage Pharma Group Inc.
Last Modified on	19 February 2024

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Eligibility		Yes	No	Not Sure
Inclusion Criteria
	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) 1.5 109/L
	Platelets 90 109/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
	Serum creatinine 1.5 x ULN or 24-hour creatinine clearance 50 mL/min (calculated according to Cockcroft-Gault formula)
	Patients with asymptomatic brain metastases (not requiring pharmacological control) or brain metastases that have been stable for more than 28 days after treatment
	Patients must have recovered to Grade 1 or less from adverse reactions resulting from prior antineoplastic therapy (except alopecia and sensory neuropathy not exceeding Grade 2)
	Males, women of childbearing potential (postmenopausal women who must have been postmenopausal for at least 12 months to be considered of non-childbearing potential) and their partners voluntarily use contraception deemed effective by the investigator during treatment and for at least three months after the last dose of study drug
	Able to understand and voluntarily sign a written informed consent form, which must be signed prior to the performance of any trial-specified study procedures
	Patients must be voluntary and able to complete study procedures and follow-up examinations
Exclusion Criteria
	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 or biologic 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 only)
	Use of anti-TNFa therapy within 28 days prior to first dose
	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 > 38.5C 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 QTcB > 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-Gurin 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
	Pregnant or lactating female patients
	The subject has other factors that may cause the subject to be forced to terminate the study, such as suffering from other serious diseases (including mental illness) requiring concomitant treatment, severe abnormalities in laboratory tests, family or social factors, conditions that may affect the safety of the subject or the collection of trial data, etc

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