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

A Multi-center, Open-label Phase II 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)

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)

Study Overview

• Status: Completed
• Conditions: Melanoma; Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: YH003; Drug: Toripalimab

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Richmond, Victoria, Australia, 3121
      • Epworth Medical Centre
• United States
  • New York
    • New York, New York, United States, 10029
      • Ichan School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

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: Nab-paclitaxel; Nab-paclitaxel will be administered each 21-day cycle.; Drug: Gemcitabine; Gemcitabine will be administrated each 21-day cycle.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Eucure (Beijing) Biopharma Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2021
• Primary Completion (Actual): August 16, 2023
• Study Completion (Actual): August 16, 2023

Study Registration Dates

• First Submitted: August 26, 2021
• First Submitted That Met QC Criteria: August 26, 2021
• First Posted (Actual): September 2, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 3, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Skin Diseases; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Adenocarcinoma; Melanoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Gemcitabine; Paclitaxel
• Other Study ID Numbers: YH003004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No