An Open-Label, Multicenter, Phase I Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of YY201 in Patients With Advanced Solid Tumors and Hematological Malignancies

NCT06225856 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 2022-YY201-CH1
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, open-label, phase I clinical study of YY201 in the patients with relapsed/refractory lymphomas and relapsed/refractory large granular lymphocytic leukemia who failed or cannot tolerate standard treatment.

Conditions

Advanced Solid Tumor; Hematological Malignancy

Outcome Measures

Primary Outcomes (4)

• 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 31 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 approximately 24 months

• Treatment-Emergent Adverse Event (TEAE)

  TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of YY201 . The type, frequency and severity of TEAE will be evaluated during the treatment of YY201 .

  Up to approximately 24 months

• 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 YY201.

  Up to 31 days after the initial drug administration

Secondary Outcomes (6)

• Cmax

  Up to 31 days after the initial drug administration

• Tmax

  Up to 31 days after the initial drug administration

• T1/2

  Up to 31 days after the initial drug administration

• Duration of Response(DoR)

  Up to approximately 24 months

• Time to Disease Response(TTR)

  Up to approximately 24 months

Study Arms (1)

Study treatment

EXPERIMENTAL

Method of Administration: Single dose period: Single oral administration under fasting state; Multiple dose period: Oral administration under fasting state, QD.

Drug: YY201

Interventions

YY201 DRUG

Oral administration under fasting state.

Study treatment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients fully understand and sign ICF, voluntarily participate in the study, and able to follow and complete all study procedures.
• Aged 18-80 years (including upper and lower limits), male or female.
• \. 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 with:
• Surgical excision is confirmed by histology or cytology can't or metastatic patients with advanced solid tumor;
• Patients with relapsed or refractory hematologic malignancies
• \. 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).
• \. In the dose-expansion phase, enrollment was limited to:
• Advanced solid tumors (predominantly triple-negative breast cancer, pancreatic cancer, and head and neck squamous cell carcinoma) that are sensitive to STAT3 therapy;
• Peripheral T-cell lymphoma (PTCL) with STAT3 mutation refractory to or relapsed after at least one or more lines of systemic therapy;
• For patients with PTCL, computed tomography performed within 28 days before study entry should show at least one measurable tumor lesion in two vertical directions, with nodal lesions \> 1.5cm in greatest dimension and extranodal lesions \> 1.0cm (according to the 2014 lugano criteria).
• Relapsed/refractory acute myeloid leukemia that is sensitive to STAT3 therapy, excluding acute promyelocytic leukemia (APL) and other secondary AML (e.g., MDS transformation, CML in blast phase, etc.)
• \. ECOG physical condition≤1.
• \. Patients with advanced primary liver cancer should meet the Child-Pugh liver function grading: grade A and better grade B (≤7).
• \. Regular check need to meet the following requirements:
• For advanced solid tumors, adequate bone marrow, liver, and kidney function is required:

You may not qualify if:

• \. 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);
• \. Clinically symptomatic parenchymal or leptomeningeal metastases that were judged by the investigator to be ineligible for enrollment and, for AML patients, known central nervous system (CNS) involvement
• \. 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;
• For peripheral blood leukocyte count (WBC \> 25 x 10\^9 / L) of the patients, allowing use in treatment of the former and YY201 hydroxyurea control peripheral blood leukocytes;
• Prophylactic intrathecal chemotherapy (cytarabine, dexamethasone, and methotrexate) unless it is used to prevent central leukemia.
• \. Received other unlisted investigational drugs or treatments within 4 weeks before the first dose;
• \. Previously received STAT3 inhibitor for anti-tumor treatment;
• \. Major organ surgery (excluding needle biopsy) within 4 weeks before the first dose of medication or requiring elective surgery during the trial;
• \. Uncontrolled malignant pleural, ascites, or pericardial effusion that was judged by the investigator to be ineligible for enrollment;
• 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;
• \. 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;
• \. 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;

Sponsors & Collaborators

• Shanghai Yuyao Biotech Co., Ltd.: lead

Study Sites (1)

Shanghai East Hospital

Shanghai, Shanghai Municipality, China

RECRUITING

MeSH Terms

Conditions

Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Ye Guo

CONTACT

13501678472; pattrickguo@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2024
• First Posted: January 26, 2024
• Study Start: October 26, 2023
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: January 31, 2024

Record last verified: 2024-01

Locations

CN (1)