Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antimetabolites

APG1387 will be administered IV days 1， 8, 15 and 22 of a 28 day cycle.

APG-1387 for Injection

Gemcitabine 1000 mg/m\^2 will be administered IV days 1, 8, and 15 of a 28 day cycle.

Nab-Paclitaxel 125mg/m\^2 will be administered IV days 1, 8, and 15 of a 28 day cycle.

Nab paclitaxel

Xianjun Yu, MD

Si Shi, PhD

Yifan Zhai, MD, PhD

This study is a two stage study consisting of a dose escalation phase Ib and a phase II study which include subjects with previously-treated, advanced pancreatic adenocarcinoma. Dose Limiting Toxicities (DLTs) and maximum tolerated dose (MTD) of APG1387 in combination with nab-paclitaxel and gemcitabine will be evaluated in the dose escalation phase Ib. Safety and efficacy of APG1387 plus gemcitabine and nab-paclitaxel will be evaluated in phase II.

The ability of tumor cells to evade apoptosis is currently a major problem in anti-tumor therapy. IAPs are an important class of apoptosis-regulating proteins. APG-1387, a potent bivalent SMAC mimetic, small molecule of IAP inhibitor, which could inhibit pancreatic cancer proliferation as monotherapy and in combination with chemotherapy through apoptosis pathway.

It's an open label, multiple centers phase Ib/II Study. Safety and tolerability of APG1387 combined with nab-paclitaxel and gemcitabine will be evaluated in phase Ib in previously-treated, advanced pancreatic adenocarcinoma patients. Efficacy and tolerability will be evaluated in phase II study in first line standard treatment failed metastatic pancreatic adenocarcinoma patients.

APG-1387 Plus Chemotherapy in Advanced Pancreatic Adenocarcinoma

An Open Label, Multiple Centers Phase Ib/II Study of APG-1387 Plus Chemotherapy in Advanced Pancreatic Adenocarcinoma

DLT will be graded according to NCI CTCAE Version 5.0. DLT will be defined as clinically significant drug-related adverse events during the cycle one.

Evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

From date of treatment start until the date of progression or the date of death due to any cause.

From date of response until the date of progression.

From date of treatment start until the date of death due to any cause.

Cmax of APG-1387 and Nab-Paclitaxel will be assessed in the patients in this study.

AUC of APG-1387 and Nab-Paclitaxel will be assessed in the patients in this study.

Adverse events (AE) and serious adverse events (SAE) will be graded according to NCI CTCAE Version 5.0.

Ascentage Pharma Group Inc.

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Open label study. All patients participating in the study will receive Debio 1143 (AT-406).

Oral Debio 1143 (AT-406) will be administered in a dose escalation study to determine the maximally tolerated dose in humans. Patients will receive Debio 1143 (AT-406) on days 1-5, and 15-19 of a 28 day cycle, or days 1-5 of a 21 day cycle, repeated until progression or unacceptable toxicity occurs.

Debio 1143 (AT-406)

Claudio Zanna, MD

The purpose of this study is to determine the safety profile and the maximum dose of Debio 1143 (AT-406) that can be given to humans. This study is also designed to measure how much Debio 1143 (AT-406) gets into the blood stream (pharmacokinetics), and how Debio 1143 (AT-406) interacts with proteins related to cancer that the drug is targeted to affect (pharmacodynamics).

Ascenta Therapeutics, Inc. is conducting a clinical trial of the compound Debio 1143 (AT-406), a small molecule second mitochondria-derived activator of caspase C (Smac) mimetic. In vivo and in vitro studies have demonstrated that Debio 1143 (AT-406) induces cell death in several tumor models by inhibiting XIAP (X linked IAP), cIAP-1 (cellular IAP-1) and cIAP-2 (cellular IAP-2), thus releasing initiator and effector caspases to promote apoptosis. This protocol is a Phase I, dose-escalation, open-label, multi-center study conducted in patients with advanced solid tumors and lymphomas to evaluate the safety, tolerability and pharmacology of Debio 1143 (AT-406) in humans when administered orally.

Dose Escalation Study of Safety and Tolerability of AT-406 in Patients With Advanced Solid Tumors and Lymphomas

A Phase I, Open Label, Multi-Center, Dose Escalation Study of the Safety, Tolerability, Pharmacodynamic and Pharmacokinetic Properties of Orally Administered AT-406 in Patients With Advanced Solid Tumors and Lymphomas

The primary endpoint of this study is to characterize the safety, and determine the maximum tolerated dose and schedule of Debio 1143 (AT-406) when administered to patients with advanced cancer. Patients will receive Debio 1143 (AT-406) on days 1-5, and 15-19 of a 28 day cycle, days 1-5 of a 21 day cycle, or days 1-14 of a 21 day cycle. For the purpose of determining the MTD, dose limiting toxicities will be evaluated at any time. For the purpose of dose escalation, dose limiting toxicities will be evaluated through the end of 1 cycle.

A secondary endpoint of this study is to determine the pharmacokinetic parameters of Debio 1143 (AT-406) in plasma and urine, and preliminary metabolism profile of Debio 1143 (AT-406).

A secondary endpoint of this study, provided that adequate amounts of tissue are available, is to evaluate the interaction of Debio 1143 (AT-406) with IAP family members (e.g., xIAP, cIAP-1, cIAP-2, etc.). Patient participation in this aspect of the study is optional.

A secondary endpoint to this study is to identify any anti-tumor activity of Debio 1143 (AT-406) that may be observed in the course of the trial. Applicable solid tumor or lymphoma response criteria will be used, accordingly.

A secondary endpoint of this study is to correlate pharmacokinetic and pharmacodynamic effects of Debio 1143 (AT-406) with any observed antitumor activity of Debio 1143 (AT-406).

Debiopharm International SA

Hematologic Neoplasms

Hematologic Diseases

APG-1387 will be explored sequentially using a standard 3+3 escalation scheme at the dose escalation phase and up to 20 patient per group at the dose expansion phase.

Multiple dose cohorts, 30 minute IV infusion, once weekly for 3 weeks of a 21-day cycle

APG-1387 is a potent, bivalent small-molecule Inhibitor of Apoptosis Protein (IAP) antagonist. APG-1387 has shown strong dose- and schedule-dependent antitumor activities in multiple human cancer xenograft models, APG-1387 also demonstrates its synergistic effect in combination with immune checkpoint inhibitor anti-PD-1 antibody, and such a combinatory effect was further enhanced by chemotherapeutic agent. A total of 35 patients with advanced solid tumors or lymphomas have been treated with APG-1387 in two Phase I dose-escalation studies in Australia and in China. Ten dose levels have been tested ranging from 0.3 mg to 45 mg in these two studies. Based on the preliminary results, APG-1387 is well-tolerated at the dose levels evaluated to date. APG-1387 is intended for the treatment of patients with advanced solid tumors and hematologic malignancies. After establishing the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and/or recommended phase 2 dose (RP2D), several Ib /II studies will be implemented accordingly to further access the antitumor effects of APG-1387 in combination with either pembrolizumab or the chemotherapeutic agents.

APG-1387 in Patients With Advanced Solid Tumors or Hematologic Malignancies

A Phase I Study of the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of APG-1387 as a Single Agent or in Combination With Systemic Anti-Cancer Agents in Patients With Advanced Solid Tumors or Hematologic Malignancies

Patients with APG-1387 treatment related adverse events (AE), serious adverse events (SAE) will be assessed according NCI CTCAE Version 4.03

Response will be evaluated every 2 cycles (8 weeks), according to the revised RECIST Guideline, Version 1.1 or the Revised Response Criteria for Malignant Lymphoma

Maximum plasma concentration (Cmax) will be assessed in the patients treated with APG-1387

Tumor biopsy and peripheral blood sample at baseline and 15-21 days after administration of APG-1387 alone or in combination with systemic anti-cancer therapy

Area under the plasma concentration versus time curve (AUC) of APG-1387 will be assessed on patients treated with APG-1387

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
APG-1387 Plus Chemotherapy in Advanced Pancreatic Adenocarcinoma	NCT04643405	Advanced Pancre...	APG-1387 for In... Gemcitabine Nab paclitaxel	18 Years -	Ascentage Pharma Group Inc.
Dose Escalation Study of Safety and Tolerability of AT-406 in Patients With Advanced Solid Tumors and Lymphomas	NCT01078649	Cancer Solid Tumors Lymphoma Malignancy	Debio 1143 (AT-...	18 Years -	Debiopharm International SA
Dose Escalation Study of Safety and Tolerability of AT-406 in Patients With Advanced Solid Tumors and Lymphomas	NCT01078649	Cancer Solid Tumors Lymphoma Malignancy	Debio 1143 (AT-...	18 Years -	Debiopharm International SA
APG-1387 in Patients With Advanced Solid Tumors or Hematologic Malignancies	NCT03386526	Advanced Solid ...	APG-1387 for In...	18 Years -	Ascentage Pharma Group Inc.

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