A Study of NWY001 in Subjects With Advanced Solid Tumors

Official title

A Multicenter, Non-randomized, Open-label, Multiple-Dose Phase I Study of NWY001, in Subjects With Advanced Solid Tumors

Overview

This is a Phase 1, single-arm, open-label, dose-escalation study in patients with advanced solid tumors including 2 parts: Part 1: Dose-Escalation Part Part 2: Dose-Expansion Part

Detailed description

Part 1: Patients with advanced solid tumors that has relapsed from or is refractory to standard therapy or for which no standard therapy exists will be enrolled in different cohorts.

Part 2: Recommended Phase 2 dose (RP2D) of NWY001 will be given to all patients enrolled in this part.

Interventions

• Biological NWY001
  Part 1: Participants will be given a single-dose of NWY001 intravenously once every 3 weeks until a discontinuation criteria was met during treatment period.
• Biological NWY001
  Part 2: Participants will be given RP2D of NWY001 intravenously once every 3 weeks until a discontinuation criteria was met during treatment period.

Primary outcome measures

• Dose-limiting toxicity (DLT) [Time frame: Up to 21 days]
• Incidence of adverse events (AEs) [Time frame: Until 30 days after the last dose of the study drug]

Secondary outcome measures (10)

• Objective response rate (ORR) [Time frame: Until 30 days after the last dose of the study drug]
• Disease control rate (DCR) [Time frame: Until 30 days after the last dose of the study drug]
• Progression free survival (PFS) [Time frame: Until 30 days after the last dose of the study drug]
• Maximum plasma concentration (Cmax) [Time frame: From pre-dose to 30 days after the last dose of the study drug]
• Time to Cmax (Tmax) [Time frame: From pre-dose to 30 days after the last dose of the study drug]
• Area under the plasma concentration-time curve from 0 to infinity (AUC 0-inf) [Time frame: From pre-dose to 30 days after the last dose of the study drug]
• Tumor necrosis factor-α (TNF-α) [Time frame: From pre-dose to 30 days after the last dose of the study drug]
• Interleukin-6 (IL-6) [Time frame: From pre-dose to 30 days after the last dose of the study drug]
• Incidence of anti-drug antibody (ADA) [Time frame: From pre-dose to 30 days after the last dose of the study drug]
• Incidence of neutralizing antibody (NAb) [Time frame: From pre-dose to 30 days after the last dose of the study drug]

Eligibility criteria

Inclusion criteria

• Willingness to sign a written informed consent document
• Participant with advanced solid malignant tumor that has relapsed from or is refractory to standard therapy or for which no standard therapy exists
• 18\~75 years of age at the time of screening
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy ≥3 months
• Laboratory tests meet the following criteria (no corrective treatment, such as G-CSF, erythropoietin, and blood transfusion, within 14 days before first dose):

1\) absolute neutrophil count (ANC) ≥1.5×109/L 2) platelet ≥100×109/L 3) hemoglobin ≥90 g/L 4) creatinine clearance >50 mL/min (according to Cockcroft-Gault equation) 5) both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5×upper limit of normal (ULN) (≤5×ULN for patients with hepatic metastasis) 6) total bilirubin ≤1.5×ULN (≤3×ULN for patients with gilbert syndrome) 7) international normalized ratio (INR) <2.0, activated partial thromboplastin time (aPTT) ≤1.5×ULN

7\. Prior anti-cancer therapy meets the following criteria:

• major surgery ≥4 weeks
• radiotherapy ≥4 weeks
• endocrine therapy ≥2 weeks
• chemotherapy (including antibody) ≥3 weeks
• immunotherapy ≥4 weeks

8\. At least one measurable target lesion as defined by RECIST1.1

9\. For part 2a: Participant has a diagnosis of histologically confirmed advanced (unresectable) or metastatic gastric or gastroesophageal junction adenocarcinoma

• participant with HER2 overexpression (IHC 3+ or IHC 2+/ISH+) is refractory or intolerant to standard therapy or for which no standard therapy exists. Prior treatment with trastuzumab or HER2-targeted drugs
• participant with no HER2 expression is refractory or intolerant to standard therapy or for which no standard therapy exists

10\. For part 2b: Participant has a diagnosis of histologically confirmed advanced esophageal squamous carcinoma

11\. For part 2c: Participant has a diagnosis of histologically confirmed advanced pancreatic ductal adenocarcinoma

12\. For part 2d: Participant has a diagnosis of histologically confirmed advanced hepatocellular carcinoma

13\. For part 2e: Participant has a diagnosis of histologically confirmed advanced intrahepatic cholangiocarcinoma

14\. For part 2f: Participant has a diagnosis of histologically confirmed advanced MSI-H/dMMR colorectal cancer

Exclusion criteria

1\. Current or previous history of other active aggressive malignancies in the last 5 years, except :

• previous history of non-aggressive malignancies, such as cervical carcinoma in situ, melanoma in situ, or ductal carcinoma in situ of the breast that remains in complete remission for years after curative treatment
• malignancies with negligible risk of metastasis or death (such as adequately treated basal or squamous cell skin cancer and focal prostate cancer)

2\. Current or previous history of hematological malignancies

3\. Primary central nervous system (CNS) malignancies or CNS metastases

4\. History of allergy or hypersensitivity to monoclonal antibodies or excipients, or a known history of allergy to antibodies produced by Chinese hamster ovary cell

5\. Uncontrolled infection that requires intravenous antibiotics, antivirals, or antifungal medications

6\. History of clinically significant lung diseases (such as interstitial pneumonia, pneumonia, pulmonary fibrosis, and severe radiation pneumonia), or patients suspected of having these diseases on radiographic examination during the screening period

7\. Uncontrolled complications, including, but not limited to, persistent active infections, active coagulopathy, uncontrolled cardiovascular disease, uncontrolled immune disease, uncontrolled diabetes, uncontrolled chest and abdominal fluid accumulation, psychiatric disorders that do not meet study requirements, and other serious conditions requiring systemic treatment

8\. Known history of HIV, active infections of hepatitis B or hepatitis C

9\. Active pulmonary tuberculosis. Participants vaccinated with BCG vaccine may be false positive for PPD, and they could be enrolled if negative for IGRA

10\. Women who are pregnant or breastfeeding or intended to become pregnant during the study period

11\. Participants of childbearing potential who refuse to take highly effective contraceptive measures during the entire study treatment period and for 120 days after the last dose of study drug

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-sen University Cancer Cancer — Guangzhou

Identifiers

NCT: NCT05979155 · NWY001-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗