A Study of YL202 in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer and Breast Cancer

Study Overview
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Brief Summary
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This is a phase 1, multicenter, open-label, first-in-human study of YL202 conducted in the United States and China. The study will evaluate the safety and tolerability of YL202 in patients with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated NSCLC or hormone receptor (HR)-positive and HER2-negative BC, which have been heavily treated by standard treatment.

Official Title
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A Phase 1, Multicenter, Open-label, First-in-human Study of YL202 in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer and Breast Cancer

Conditions
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Non Small Cell Lung Cancer, Breast Cancer

Intervention / Treatment
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* Drug: YL202


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed of the trial before the start of the trial and voluntarily sign their name and date on the informed consent form Aged ≥18 years Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2 Adequate organ and bone marrow function Female patients of childbearing potential must agree to use a highly effective form of contraception and not donate, or retrieve for their own use, ova from the time of screening and throughout the study period, and for at least 6 months after the last dose of study drug. Male patients must agree to use a highly effective form of contraception and not freeze or donate sperm from the time of screening and throughout the study period, and for at least 6 months after the last dose of study drug. Life expectancy of ≥3 months Able and willing to comply with protocol visits and procedures For NSCLC patients: Have a histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC not amenable to curative surgery or radiation Have a documentation of an EGFR-activating mutation (exon 19 deletion or L858R) detected at diagnosis or thereafter Have documentation of disease progression on or after, or are intolerant to prior standard treatment regimens for locally advanced or metastatic disease. For BC patients: Have a histologically or cytologically confirmed diagnosis of unresectable locally advanced or metastatic HR-positive and HER2-negative BC (per American Society of Clinical Oncology-College of American Pathologists [ASCO-CAP] guidelines) Have documentation of disease progression on or after, or are intolerant to prior standard treatment regimens for locally advanced or metastatic disease. Have at least 1 measurable tumor lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Exclusion Criteria: Intolerant to prior treatment with a topoisomerase I inhibitor or an ADC that consists of a topoisomerase I inhibitor, including but not limited to topotecan, irinotecan, and DXd (e.g., severe diarrhea) Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study Inadequate washout period for prior anticancer treatment before the first dose of study drug Undergone major surgery (not including diagnostic surgery) within 4 weeks before the first dose of study drug or expect major surgery during the study Prior allogeneic bone marrow transplantation or solid-organ transplantation Received systemic steroids (>10 mg/day of prednisone or its equivalent) or other immunosuppressive therapy within 2 weeks before the first dose of study drug. The following are exceptions to this criterion: Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) Systemic steroids at physiological doses as replacement therapy (e.g., physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication) Received any live vaccine within 4 weeks before the first dose of study drug or intend to receive a live vaccine during the study A history of leptomeningeal carcinomatosis Brain metastases or spinal cord compression unless asymptomatic or treated and stable off steroids and anti-convulsants for at least 2 weeks before the first dose of study drug Uncontrolled or clinically significant cardiovascular disease. A history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that requires steroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening Clinically significant concomitant pulmonary disease. Clinically significant corneal disease Have a diagnosis of Gilbert's syndrome Uncontrolled third-space fluid (e.g., pleural effusions, ascites, pericardial effusions) that requires repeated drainage Active gastric and duodenal ulcers, ulcerative colitis, or other gastrointestinal conditions that may cause bleeding or perforation by the investigator's discretion Active infection that requires systemic therapy within 1 week before the first dose. Patients receiving prophylactic anti-infective therapy (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) may be eligible after discussion with the sponsor. Known human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Patients with HIV, HBV, or HCV infection may be enrolled after evaluation of eligibility based on FDA's guideline Cancer Clinical Trial Eligibility Criteria: Patients with HIV, Hepatitis B Virus, or Hepatitis C Virus Infections Any other primary malignancy within 3 years before the first dose of study drug, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other curatively treated solid tumors Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia and pigmentation) not yet resolved to NCI CTCAE Grade ≤1, baseline, or the level specified in the inclusion/exclusion criteria. Patients with chronic Grade 2 toxicities who are asymptomatic or adequately managed with stable medication may be eligible after discussion with the sponsor. A history of severe hypersensitivity reactions to the drug substances, inactive ingredients in the drug product, or other monoclonal antibodies Women who are breastfeeding or pregnant as confirmed by pregnancy tests performed within 3 days before the first dose Any illness, medical condition, organ system dysfunction, or social situation, including but not limited to mental illness or substance/alcohol abuse, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, adversely affect the patient's ability to cooperate and participate in the study, or compromise the interpretation of study results.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: YL202 Dose escalation<br>YL202 will be administrated intravenously (IV) per dose level in which the patients are assigned. | Drug: YL202<br>* YL202 is provided as the lyophilized powder, 200 mg/vial. YL202 will be given intravenously once every 3 weeks (Q3W) as a cycle. The initial dose of YL202 will be infused IV into each patient for 90 ±10 minutes. If there is no infusion-related reaction after the initial dose, the second and subsequent doses of YL202 will be infused IV into each patient for 60 ±10 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the occurrence of DLTs during the first cycle |  | At the end of Cycle 1 (each cycle is 21 days) | 
| Evaluate the AEs as characterized by type, frequency, severity, timing, seriousness and relationship to study treatment |  | By the global end of trial date, approximately within 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize the PK parameter AUC |  | Approximately within 36 months | 
| Characterize the PK parameter Cmax |  | Approximately within 36 months | 
| Characterize the PK parameter Ctrough |  | Approximately within 36 months | 
| Characterize the PK parameter CL |  | Approximately within 36 months | 
| Characterize the PK parameter Vd |  | Approximately within 36 months | 
| Characterize the PK parameter t1/2 |  | Approximately within 36 months | 
| Assess the incidence of anti-YL202 antibodies |  | Approximately within 36 months | 
| Evaluate the objective response rate (ORR) | ORR: defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR). | Approximately within 36 months | 
| Evaluate the disease control rate (DCR) | DCR: defined as the proportion of patients who achieved a best overall response of CR, PR or stable disease (SD). | Approximately within 36 months | 
| Evaluate the best tumor response | Best tumor response: defined as the maximum percentage change in the sum of longest dimensions of measurable lesion(s) at any time during the study. | Approximately within 36 months |