A Study to Evaluate YH003 in Combination With Toripalimab (Anti-PD-1 mAb) in Subjects With Advanced Solid Tumors

NCT04481009 | Completed Phase 1 DMC

• 1 other identifier: YH003002
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I/II, multi-center, open-label study of YH003 in combination with Toripalimab (anti-PD-1 mAb). The study is comprised of a dose escalation part (Part I) exploring escalating doses of YH003 in combination with fixed dose toripalimab in subjects with advanced solid tumors (Part I), followed by an expansion part (Part II) with three expansion cohorts.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Overall safety and tolerability profile of YH003 in combination with Toripalimab.

  The safety profile of YH003 in combination with Toripalimab will be assessed by monitoring the adverse events (AE) per NCI CTCAE v5.0

  From screening up to 1 year

• Maximum tolerated dose (MTD) and Recommended phase 2 dose (RP2D)

  The MTD and RP2D will be determined based on the data of safety and tolerability

  Cycle 1 of each cohort. Duration of one cycle is 3 weeks

Secondary Outcomes (18)

• Area under the serum concentration versus time curve (AUC)

  Up to 1 year

• Maximum serum concentration (Cmax)

  Up to 1 year

• Trough concentration before the next dose is administered (Ctrough)

  Up to 1 year

• Time to reach maximum serum concentration (Tmax)

  Up to 1 year

• Clearance (CL)

  Up to 1 year

Study Arms (3)

YH003 with Toripalimab after PD-1/L1 +/- CTLA-4 treatment

EXPERIMENTAL

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

Drug: YH003; Drug: Toripalimab

YH003 with Toripalimab in subjects with PDAC

EXPERIMENTAL

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

Drug: YH003; Drug: Toripalimab

YH003 with Toripalimab plus standard chemotherapy

EXPERIMENTAL

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

Drug: YH003; Drug: Toripalimab; Drug: Nab-paclitaxel; Drug: Gemcitabine

Interventions

YH003 DRUG

YH003 will be administered intravenously over 60 minutes every 21-day cycle.

YH003 with Toripalimab after PD-1/L1 +/- CTLA-4 treatment; YH003 with Toripalimab in subjects with PDAC; YH003 with Toripalimab plus standard chemotherapy

Toripalimab DRUG

Toripalimab with fixed dose of 240 mg administered intravenously followed by YH003 administered intravenously every 21-day cycle.

YH003 with Toripalimab after PD-1/L1 +/- CTLA-4 treatment; YH003 with Toripalimab in subjects with PDAC; YH003 with Toripalimab plus standard chemotherapy

Nab-paclitaxel DRUG

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

YH003 with Toripalimab plus standard chemotherapy

Gemcitabine DRUG

Gemcitabine will be administrated each 21-day cycle.

YH003 with Toripalimab plus standard chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have the ability to understand and willingness to sign a written informed consent document.
• Part I dose escalation:
• Have histologically advanced or cytologically confirmed solid tumor. Have progressed on after treatment with at least one standard therapy or intolerant of the standard therapy.
• Part II dose expansion:
• Cohort 2A: Histologically or cytologically confirmed unresectable or metastatic melanoma that had confirmed progressive disease during treatment with an anti-PD-1/PD-L1 therapy with or without additional CTLA-4 therapy. Subjects with BRAF activating mutation could have also received a BRAF inhibitor and/or MEK inhibitor regimen prior to anti-PD-1/PD-L1 therapy.
• Cohort 2B, 2C: Subject has histologically or cytologically documented diagnosis of pancreatic ductal adenocarcinoma with unresectable locally advanced/metastatic disease Cohort 2B: had confirmed progressive disease during treatment with first line standard of care of chemotherapy per local standard.
• Cohort 2C: treatment-naïve for unresectable locally advanced/metastatic disease.
• Subject must have measurable disease by RECIST 1.1. At least 1 unidimensional measurable target lesion per RECIST v1.1 for study Part II expansion cohorts.
• Subjects must be age 18 years or older.
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Life expectancy ≥3 months.
• Subjects must have adequate organ function.
• Women of reproductive potential must have negative serum beta human chorionic gonadotropin (β -HCG) pregnancy test.

You may not qualify if:

• Part II Cohort 2A: History of life-threatening toxicity or treatment discontinuation due to related to prior anti-PD-1/PD-L1 and with or without CTLA-4 combination treatment for subjects with unresectable/metastatic melanoma.
• Subjects must not have another active invasive malignancy.
• Previous exposure to TNFR such as anti-CD137, OX40, CD27 and CD357 antibodies.
• 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.
• Subjects with a history of ≥ Grade 3 immune-related adverse events resulted from previous immunotherapy.
• 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. Also history of severe hypersensitivity reaction to Nap-paclitaxel and/or gemcitabine.
• Primary central nervous system (CNS) malignancies or symptomatic CNS metastases.
• History of (non-infectious) pneumonitis that required corticosteroids or current pneumonitis, or history of interstitial lung disease.
• Subjects must not have a known or suspected history of an autoimmune disorder, including but not limited to inflammatory bowel disease, celiac disease, Wegner syndrome, Hashimoto syndrome, systemic lupus erythematosus, scleroderma, sarcoidosis, or autoimmune hepatitis, within 3 years of the first dose of study treatment.
• Clinically uncontrolled intercurrent illness, including an ongoing or active infection, active coagulopathy, uncontrolled diabetes, psychiatric illness that would limit compliance with the study requirements and other serious medical illnesses requiring systemic therapies.
• 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.
• QTc \> 450 ms at baseline; no concomitant medications that would prolong the QT interval; no family history of long QT syndrome.
• Subjects must not have active infection of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
• Subjects must not have a history of primary immunodeficiency.
• Subjects from endemic area will be specifically screened for tuberculosis. Subjects with active tuberculosis are excluded.

Sponsors & Collaborators

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

Study Sites (1)

Linear Clinical Research

Nedlands, Western Australia, 6009, Australia

Location

MeSH Terms

Interventions

toripalimab; 130-nm albumin-bound paclitaxel; Gemcitabine

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2020
• First Posted: July 22, 2020
• Study Start: August 4, 2020
• Primary Completion: May 16, 2022
• Study Completion: May 26, 2022
• Last Updated: December 12, 2022

Record last verified: 2022-10

Locations

AU (1)