A Study to Assess the Safety, Pharmacokinetics, and Preliminary Efficacy of ATG 016 Monotherapy in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is A Phase Ib/II Study to Assess the Safety, Pharmacokinetics, and Preliminary Efficacy of ATG 016 Monotherapy in Patients with Advanced Solid Tumors

Detailed Description
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This is A Phase Ib/II Open-label, Multi-centre, Dose Finding Study to Assess the Safety, Pharmacokinetics, and Preliminary Efficacy of ATG 016 Monotherapy in Patients with Advanced Solid Tumors

Official Title
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A Phase Ib/II Open-label, Multi-centre, Dose Finding Study to Assess the Safety, Pharmacokinetics, and Preliminary Efficacy of ATG 016 Monotherapy in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: ATG-016


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Understand and voluntarily sign informed Consent (ICF) prior to any assessment/procedure related to study. Age ≥18 years at ICF signature. Estimated life expectancy of minimum of 12 weeks. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at ICF signature. Subjects must have at least one measurable lesion as defined by RECIST version 1.1. Females of childbearing potential must agree to use effective contraception from the time ICF signature until 180 days after the last dose. Females of childbearing potential include those who are premenopausal and those who are 2 years postmenopausal. Blood pregnancy tests must be negative for female of childbearing potential must have a negative serum pregnancy test at Screening. Inclusion Criteria Only for Phase Ib study (Dose Escalation and Expansion phase) 1. Histological or cytological confirmation of a solid tumor, and have progressed despite standard therapy(ies), or are intolerant to standard therapy(ies), or have no standard therapy(ies) exists. Inclusion Criteria Only for Phase II Penile squamous cell carcinomas confirmed by cytology or histology cannot be excised by radical surgery, or postoperative recurrence or metastasis which is not suitable for platinum chemotherapy or platinum resistance or platinum failure. Nasopharyngeal carcinoma Exclusion Criteria: Subjects with any of the following conditions will not be enrolled in this study. Central nervous system (CNS) metastases and involvement. A history of bone marrow or organ transplantation. Prior ATG-016 administration or other XPO1 inhibitor treatment. Known to be allergic to the active or inactive ingredients of ATG-016 or drugs with similar chemical structure, or the subject is hypersensitive. Prior therapy with any investigational drugs or systemic anticancer treatment (eg, a period of 5 'half-lives' of drugs, whichever is longer) within 28 days at the time of ICF signature. Received extensive radiation within 28 days at the time of ICF signature or expect to undergo radical radiotherapy during the study period. Received major surgery within 28 days at the time of ICF signature or expect to proceed a major surgical treatment during the study period. Any toxicities unresolved to Grade 1 or baseline from prior anti-tumor therapy (According to NCI-CTCAE 5.0) with the exception of alopecia, within 28 days at the time of ICF signature. Any uncontrolled active infection requiring parenteral treatment of antibiotics, antivirals, or antifungals at the time of ICF signature or within one week of Cycle 1 Day 1 (C1D1). Active hepatitis B virus (HBV) infection (Hepatitis B surface antigen [HBsAg] positive) or active HCV infection (HCV-RNA positive at screening). A history of HIV infection and/or acquired immunodeficiency syndrome. Received immunosuppressive medication within 14 days at the time of ICF signature. Cardiovascular diseases of clinical significance Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: Have a history of another primary malignancy within 5 years prior to starting study treatment, with following exceptions: malignancy tumors treated by radical therapy and have not been recurred, such as carcinoma in situ of the cervix, basal cell carcinoma or squamous cell carcinoma of the skin, papillary thyroid carcinoma, etc. Inability or unwillingness to comply with the requirement for oral drug administration, or presence of a gastrointestinal diseases or other clinical conditions that would compromise the absorption of study drug, eg, refractory nausea and vomiting, inability to swallow the formulated product, or previous significant bowel resection, etc. Active or a history of bleeding within 6 months. Received any live attenuated vaccination within 28 days at the signature of ICF. Judgment by the investigator that the subject should not participate in the study by consideration of the complications or other conditions which might affect their adherence to the protocol. Female subjects who are pregnant or lactating.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATG-016-20mg<br>20 mg QD×5/ week as the initial dose in the Dose Escalation Phase, with a treatment cycle of 21 days,1-5/week will be the initial dose of this study | Drug: ATG-016<br>* 48 patients enrolled, orally, each 3 week (21-day) a cycle<br>|
| Experimental: ATG-016-35mg<br>35 mg QD×5/ week as the initial dose in the Dose Escalation Phase, with a treatment cycle of 21 days,1-5/week will be the initial dose of this study | Drug: ATG-016<br>* 48 patients enrolled, orally, each 3 week (21-day) a cycle<br>|
| Experimental: ATG-016-50mg<br>50 mg QD×5/ week as the initial dose in the Dose Escalation Phase, with a treatment cycle of 21 days,1-5/week will be the initial dose of this study | Drug: ATG-016<br>* 48 patients enrolled, orally, each 3 week (21-day) a cycle<br>|
| Experimental: ATG-016-65mg<br>65 mg QD×5/ week as the initial dose in the Dose Escalation Phase, with a treatment cycle of 21 days,1-5/week will be the initial dose of this study | Drug: ATG-016<br>* 48 patients enrolled, orally, each 3 week (21-day) a cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD in Phase I | MTD will be evaluated using the NCI-CTCAE, Version 5.0 | 16 months | 
| RP2D in Phase I | RP2D will be determined under the guidance of the SRC. | 16 months | 
| AEs | Toxicity will be graded according to the NCI CTCAE, Version 5.0. | 25 months | 
| SAEs | Toxicity will be graded according to the NCI CTCAE, Version 5.0. | 25 months | 
| ORR in Phase II | Based on 2006 IWG Response Criteria, evaluated by IRC: ORR (CR + PR + mCR) | 25 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) in Phase I/II | DCR (CR + PR + mCR + HI + SD) | 16 months | 
| Duration of Response (DOR) in Phase I/II | To evaluate duration of response | 12 months | 
| Overall Survival (OS） | The estimates of Kaplan-Meier | 12 months |