An Phase I Study of YY001 in Patients With Advanced Solid Tumors

An Open-Label Phase I Study to Evaluate the Safety,Tolerability and Preliminary Efficacy of YY001 in Patients With Advanced Solid Tumors

The safety and tolerability of YY001 in the treatment of patients with advanced solid tumors were evaluated, and the possible dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) or recommended phase II clinical dose (RP2D) were observed.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: YY001

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Shanghai East Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1.Patients fully understand and sign ICF, voluntarily participate in the study, and able to follow and complete all study procedures.
• 2. Aged 18-75 years (including upper and lower limits), male or female.
• 3. Patients with histologically or cytologically confirmed advanced unresectable or metastatic solid tumors (mainly gastrointestinal tumors such as colorectal cancer and gastric cancer, and prostate cancer)
• 4.The standard treatment failure (disease progression after treatment or treatment side effects not tolerance), or top treatment, or shall not apply to the current standard treatment for patients
• 5. For patients with advanced solid tumors (dose-escalation phase), at least one tumor lesion that could be evaluated according to RECIST, version 1.1; (Dose-expansion phase) At least one measurable tumor lesion according to RECIST, version 1.1 (a tumor that is located in the previously irradiated area or another locoregional treatment site and is generally not considered a measurable lesion unless there is definite progression or persistence beyond 3 months of radiation);
• 6. ECOG physical condition≤1
• 7. Patients with advanced primary liver cancer should meet the Child-Pugh liver function grading: grade A and better grade B (≤7).

• 8. With adequate bone marrow, liver and kidney organ function:

  •Blood system within 14 days (not received blood transfusions or hematopoietic stimulating factor treatment): Absolute neutrophil count (ANC) ≥1.5×10^9/L; Platelet count (PLT) ≥75×10^9/L; Hemoglobin (Hb) ≥85g/L;

  •Liver function: Total bilirubin (TBIL) ≤1.5×ULN; Alanine aminotransferase (ALT) ≤3×ULN; Spread to the liver or liver cancer patient: 5 or less x ULN; Aspartate aminotransferase (AST) or less 3 x ULN; Spread to the liver or liver cancer patient: 5 or less x ULN;

  •Renal function: Creatinine (Cr) or less 1.5 x ULN; Creatinine clearance (Ccr) (calculated only when creatinine > 1.5× ULN) ≥50ml/min (calculated according to Cockcroft-Gault formula);

  •Blood coagulation function: Activated partial thromboplastin time (APTT) ≤1.5×ULN; International normalized ratio (INR) ≤1.5×ULN;

  •Urinary protein: Urine routine /24 hours urine protein qualitative ≤1+; Or urine protein qualitative ≥2+, 24 hours urine protein < 1g;

• 9. Expected survival of at least 3 months.
• 10. Women of childbearing potential had to have a negative serum or urine pregnancy test within 7 days before the first dose. Fertile male or female patients voluntarily during the study period and at the end of the study drug within 30 days of using effective birth control methods, such as abstinence, the double protective screen type cuts, condoms, contraceptive method of oral or injected contraceptives, intrauterine device, etc. All female patients will be considered fertile unless the female patient has undergone natural menopause, artificial menopause, or sterilization (e.g., hysterectomy, bilateral adnophorectomy, or radioactive ovarian irradiation).

Exclusion Criteria:

• 1. The adverse reactions of previous antineoplastic therapy have not recovered to CTCAE 5.0 grade ≤1 (except for toxicities without safety risks judged by investigators, such as alopecia, grade 2 peripheral neurotoxicity, and hypothyroidism stable with hormone replacement therapy);
• 2. Clinically symptomatic parenchymal or leptomeningeal metastases that were judged by the investigator to be ineligible for enrollment;

• 3. Within 4 weeks before delivery for the first time received chemotherapy, radiation therapy, biological therapy and endocrine therapy, immune therapy, such as antitumor drugs, with the exception of the following situations:

  • Nitrosourea or mitomycin C within 6 weeks before first use of study drug;
  • Oral fluorouracils and small-molecule targeted agents are administered 2 weeks before first use of the study drug or within the five half-lives of the drug, whichever is longer;
  • Have antitumor indications for the study of the first use of drugs of traditional Chinese medicines before 2 weeks;
• 4. Received other unlisted investigational drugs or treatments within 4 weeks before the first dose;
• 5. Previously received EP4 inhibitor (e.g. AN0025(E7046),LY3127760,ONO-4578) for anti-tumor treatment;
• 6. Major organ surgery (excluding needle biopsy) within 4 weeks before the first dose of medication or requiring elective surgery during the trial;
• 7. Uncontrolled malignant pleural, ascites, or pericardial effusion that was judged by the investigator to be ineligible for enrollment;
• 8. Unable to oral drug swallowing, or by the researchers determine the condition of the seriously affect the gastrointestinal tract absorption, including but not limited to, such as inflammatory bowel disease (crohn's disease and ulcerative colitis, for example), or malabsorption syndrome, or chronic diarrhea;
• 9. Patients who received a potent inducer or inhibitor of CYP3A4 within 1 week before the first dose or who required continued treatment with these drugs during the study;
• 10.Patients with active gastric and duodenal ulcer, ulcerative colitis and other gastrointestinal diseases, or unresected tumor with active bleeding, or other conditions that may cause gastrointestinal bleeding or perforation as judged by the investigator;
• 11.Thromboembolic events (including stroke events and/or transient ischemic attack) occurred within 12 months before the first dose of medication;
• 12.Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction, severe/unstable angina, or coronary artery bypass grafting within 6 months before the first dose of medication; Congestive heart failure with New York Heart Association (NYHA) grade ≥2; Left ventricular ejection fraction (LVEF) <50%; A history of primary cardiomyopathy, clinically significant prolongation of the QTc interval, or a screening QTc interval >470ms in women and >450ms in men;
• 13.Patients with active or previous autoimmune diseases with potential recurrence (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), excluding patients with clinically stable autoimmune thyroid diseases and type I diabetes mellitus;
• 14.Prior immunotherapy with grade ≥3 irAE or grade ≥2 immune-related myocarditis;
• 15.Researchers to determine the clinical significance of 3 or more electrolyte abnormalities
• 16.Patients with active infection requiring antiinfective treatment or unexplained fever (body temperature >38.5 ° C) during screening or before the first dose of medication;
• 17.Patients with active pulmonary tuberculosis (TB) who were receiving anti-TB treatment or had received anti-TB treatment within 1 year before the first dose; Known human immunodeficiency virus (HIV) infection; Patients with a history of hepatitis B were in the stage of active infection (HBsAg positive and HBV-DNA > the detection limit of the research center); Patients with a history of hepatitis C were in the active infection stage, defined as positive HCV antibody test and detectable HCV RNA;
• 18.Women who are pregnant (positive pregnancy test within 14 days before medication) or are breastfeeding
• 19.Patients with known alcohol or drug dependence;
• 20.Patients judged by the investigator that may not be able to comply with all study procedures;
• 21.Any other disease, metabolic abnormality, abnormal physical examinations or laboratory abnormality with significant clinical significance. Investigator reasonably suspects that the patient has a disease or state that is not suitable for using of the study drug, or will affect interpretation of study results, or put the patient at high risk.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study treatment; Method of Administration: Single dose period: Single oral ; Multiple dose period: Oral , QD.	Drug: YY001; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicity	The incidence and severity of adverse events (TEAE) during treatment were graded according to the National Cancer Institute Standard for Common Terminology for Adverse Events (NCI-CTCAE, v5.0)	Up to 24 days after the initial drug administration
Maximum tolerated dose	In the dose increment stage, the highest dose whose estimated DLT rate is closest to the target DLT rate but does not exceed the upper bound of the equivalent interval of DLT rate is selected as MTD.	Up to 24 days after the initial drug administration
Recommended Dose for Phase II Clinical Studies (RP2D)	The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of YY001.	Up to 24 days after the initial drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response(DoR)	The time from the patient's first objective response to the patient's disease recurrence, progression, or death.	Up to approximately 24 months
Overall Survival (OS)	The time from start date of study drug to death due to any cause.	Up to approximately 24 months

Collaborators and Investigators

• Sponsor: Shanghai Yuyao Biotech Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2022
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): May 30, 2024

Study Registration Dates

• First Submitted: January 17, 2024
• First Submitted That Met QC Criteria: January 18, 2024
• First Posted (Actual): January 29, 2024

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 28, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 2021-YY001-CH1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No