A Study To Assess YH003 In Combination With Toripalimab(anti-PD-1 MAb) Injection In Patients With Cancers

Study Overview

A Study to Assess YH003 in Combination with Toripalimab(anti-PD-1 MAb) Injection in Patients with Cancers

A phase II, multi-center, open-label study to evaluate the safety and efficacy of YH003 in combination with Toripalimab (anti-PD-1 mAb) in patients with unresectable/metastatic melanoma and pancreatic ductal adenocarcinoma (PDAC)

N/A

Melanoma
Pancreatic Ductal Adenocarcinoma

DRUG: YH003
DRUG: Toripalimab
DRUG: Nab-paclitaxel
DRUG: Gemcitabine

YH003004

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2021-08-26	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-01-03
First Submitted that Met QC Criteria 2021-08-26	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-01-06
First Posted (ACTUAL) 2021-09-02	Results First Posted N/A	Last Verified 2025-01

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: YH003 with Toripalimab in subjects with unresectable /metastatic melanoma YH003 in combination with Toripalimab in subjects with unresectable /metastatic melanoma after having failed PD-1/L1 +/- CTLA-4 treatment;	DRUG: YH003 YH003 will be dosed at RP2D every 3 weeks. The first infusion of YH003 should be administered over 60 minutes. DRUG: Toripalimab Toripalimab will be administered at a dose of 240 mg every 3 weeks.
EXPERIMENTAL: YH003 with Toripalimab in subjects with PDAC YH003 in combination with Toripalimab in subjects with unresectable/ metastatic pancreatic ductal adenocarcinoma (PDAC) as 2nd line treatment;	DRUG: YH003 YH003 will be dosed at RP2D every 3 weeks. The first infusion of YH003 should be administered over 60 minutes. DRUG: Toripalimab Toripalimab will be administered at a dose of 240 mg every 3 weeks.
EXPERIMENTAL: YH003 with Toripalimab plus standard chemotherapy YH003 in combination with Toripalimab plus standard chemotherapy (Nab-paclitaxel + Gemcitabine) in subjects with unresectable/metastatic PDAC as 1st line treatment;	DRUG: YH003 YH003 will be dosed at RP2D every 3 weeks. The first infusion of YH003 should be administered over 60 minutes. DRUG: Toripalimab Toripalimab will be administered at a dose of 240 mg every 3 weeks. DRUG: Nab-paclitaxel Nab-paclitaxel will be administered each 21-day cycle. DRUG: Gemcitabine Gemcitabine will be administrated each 21-day cycle.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: YH003 with Toripalimab in subjects with unresectable /metastatic melanoma

YH003 in combination with Toripalimab in subjects with unresectable /metastatic melanoma after having failed PD-1/L1 +/- CTLA-4 treatment;

DRUG: YH003

YH003 will be dosed at RP2D every 3 weeks. The first infusion of YH003 should be administered over 60 minutes.

DRUG: Toripalimab

Toripalimab will be administered at a dose of 240 mg every 3 weeks.

EXPERIMENTAL: YH003 with Toripalimab in subjects with PDAC

YH003 in combination with Toripalimab in subjects with unresectable/ metastatic pancreatic ductal adenocarcinoma (PDAC) as 2nd line treatment;

DRUG: YH003

YH003 will be dosed at RP2D every 3 weeks. The first infusion of YH003 should be administered over 60 minutes.

DRUG: Toripalimab

Toripalimab will be administered at a dose of 240 mg every 3 weeks.

EXPERIMENTAL: YH003 with Toripalimab plus standard chemotherapy

YH003 in combination with Toripalimab plus standard chemotherapy (Nab-paclitaxel + Gemcitabine) in subjects with unresectable/metastatic PDAC as 1st line treatment;

DRUG: YH003

YH003 will be dosed at RP2D every 3 weeks. The first infusion of YH003 should be administered over 60 minutes.

DRUG: Toripalimab

Toripalimab will be administered at a dose of 240 mg every 3 weeks.

DRUG: Nab-paclitaxel

Nab-paclitaxel will be administered each 21-day cycle.

DRUG: Gemcitabine

Gemcitabine will be administrated each 21-day cycle.

Primary Outcome Measures	Measure Description	Time Frame
Confirmed Objective Response Rate (ORR)	Overall Response Rate (ORR) by investigator's assessment according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	up to 1 year after the last dosing

Secondary Outcome Measures	Measure Description	Time Frame
Adverse events (AE)	The safety profile of YH003 in combination with Toripalimab will be assessed by monitoring the adverse events (AE) per NCI CTCAE v5.0	up to 1 year after the last dosing
Duration of response (DOR)	To assess the antitumor activity of YH003 in combination with Toripalimab	up to 1 year after the last dosing
Time to response (TTR)	To assess the antitumor activity of YH003 in combination with Toripalimab	up to 1 year after the last dosing
Progression free survival (PFS)	To assess the antitumor activity of YH003 in combination with Toripalimab	up to 1 year after the last dosing
Disease control rate (DCR)	To assess the antitumor activity of YH003 in combination with Toripalimab	up to 1 year after the last dosing
Duration of disease control (DDC)	To assess the antitumor activity of YH003 in combination with Toripalimab	up to 1 year after the last dosing
Overall survival (OS)	To assess the antitumor activity of YH003 in combination with Toripalimab	up to 1 year after the last dosing
Incidence of neutralizing antibodies (NAbs)	To assess the immunogenicity of YH003 in combination with Toripalimab	up to 1 year after the last dosing

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

To be eligible for study entry patients must satisfy all of the following criteria:
1. Subjects must have the ability to understand and willingness to sign a written informed consent document.
2. Histologically or cytologically confirmed unresectable or metastatic melanoma and pancreatic ductal adenocarcinoma
Cohort 2A: had confirmed progressive disease during treatment with an anti-PD-1/PD-L1 with or without CTLA-4 therapy.
Cohort 2B: had confirmed progressive disease during treatment with first line standard of care chemotherapy per local guideline.
Cohort 2C: must not have received any prior systematic treatment, including chemotherapy, biological therapy, or targeted therapy for unresectable locally advanced/ metastatic pancreatic duct adenocarcinoma.
3. Subject must have at least 1 unidimensional measurable disease by RECIST 1.1.
4. Subjects must be age between 18 years.
5. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Life expectancy ≥3 months.
7. Subjects must have adequate organ function

Subjects who meet any of the following criteria cannot be enrolled:
1. Cohort 2A: History of life-threatening toxicity or treatment discontinuation due to related to prior anti-PD-1/PD-L1 with or without CTLA-4 treatment for subjects with unresectable/ metastatic melanoma
2.Subjects have another active invasive malignancy within 5 years, with the following exceptions and notes:
3. Previous exposure to TNFR such as anti-CD137, OX40, CD27 and CD357 antibodies.
4. Subjects must not have received any anticancer therapy or another investigational agent within the shorter of 4 weeks or 5 half-lives before the first dose of the study treatment.
5. Subjects with a history of ≥ Grade 3 immune-related adverse events resulted from previous immunotherapy or treatment discontinuation due to previous immunotherapy. .
6. History of clinically significant sensitivity or allergy to monoclonal antibodies and their excipients or known allergies to antibodies produced from Chinese hamster ovary cells, which in the opinion of the Investigator suggests an increased potential for an adverse hypersensitivity to YH003 or Toripalimab. (For cohort 2C: history of severe hypersensitivity reaction to Nap-paclitaxel and/or gemcitabine).
7. Primary central nervous system (CNS) malignancies or symptomatic CNS metastases.
8. History of (non-infectious) pneumonitis that required corticosteroids or current pneumonitis, or history of interstitial lung disease.
9. Active, hemodynamically significant pulmonary embolism within 12 weeks prior to the first dose of study drug.
10. Subjects must not have a known or suspected history of an autoimmune disorder
11. Clinically uncontrolled intercurrent illness,
12. Severe cardiovascular disease including symptomatic congestive heart failure (New York Heart Association class III or IV), unstable angina, uncontrolled hypertension, cardiac arrhythmia, a history of myocardial infarction within 6 months or a history of arterial thromboembolic event and pulmonary embolism within 3 months of the first dose of investigational agent.
13. QTc > 480 ms (Fridericia equation) at baseline; no concomitant medications that would prolong the QT interval; no family history of long QT syndrome.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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