FDA Lifts Partial Clinical Hold on Phase 1 YL202 Trial in NSCLC and Breast Cancer

• The partial clinical hold placed on the phase 1 YL202-INT-101-01 trial (NCT05653752) of YL202 (BNT326) has been lifted by the FDA.
• This study is evaluating treatment with the antibody-drug conjugate (ADC) in patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR mutations or hormone receptor (HR)-positive/HER2-negative breast cancer.
• Trial enrollment will resume in the US; however, patients will not be enrolled in dose cohorts higher than 3 mg/kg of YL202.

The FDA has lifted the partial clinical hold on the phase 1 YL202-INT-101-01 trial, which is investigating YL202 as a treatment for locally advanced or metastatic NSCLC with EGFR mutations, as well as HR-positive/HER2-negative breast cancer.¹

In June 2024, the FDA initiated the partial clinical hold as there was a potential risk of illness or injuries when YL202 was given to patients at a higher dose level. Specifically, 5 patients treated in YL202-INT-101-01 and the phase 2 YL202-CN-201-01 trial (NCT06107686) had grade 5 adverse effects (AEs).²

Following the placement of the partial clinical hold, MediLink Therapeutics, the sponsor of the study, conducted a thorough data analysis, revised the investigator brochure and patient informed consent documents, and made protocol adjustments to the YL202-INT-101-01 trial. These changes introduced risk-mitigation strategies such as dose adjustments, delays, and reductions, along with preventative measures to manage treatment-related AEs (TRAEs). The data for YL202 revealed a dose-dependent increase in TRAEs, including a decline in neutrophil counts and a higher occurrence of mucositis.

Now that the partial clinical hold has been lifted, enrollment in the trial will resume in the US. Dose cohorts higher than 3 mg/kg of YL202 will not enroll patients.¹

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About the YL202-INT-101-01 Trial

The open-label, multicenter, first-in-human YL202-INT-101-01 study is evaluating the ADC YL202 for the treatment of patients aged 18 years or older with histologically or cytologically confirmed, locally advanced or metastatic NSCLC that harbors an EGFR exon 19 deletion or exon 21 L858R mutation, as well as for patients who have experienced disease progression on or after, or were intolerant to, prior standard therapies. Patients with histologically or cytologically confirmed, unresectable locally advanced or metastatic HR-positive/HER2-negative breast cancer who had disease progression on or after, or were intolerant to, standard therapies also are being included in the study.³

Additional eligibility criteria require patients to have an ECOG performance status of 0 to 2, adequate organ and bone marrow function, a life expectancy of 3 months or more, and at least 1 measurable tumor lesion per RECIST 1.1 criteria to be included in the trial.

YL202 is being administered intravenously to all patients once every 3 weeks.

The primary end points of the study are AEs and the incidence of dose-limiting toxicities. Secondary end points consist of pharmacokinetics, objective response rate, disease control rate, and best tumor response.

In addition to this study, the phase 2 YL202-CN-201-01 trial is also assessing treatment with YL202. Patients with select locally advanced or metastatic solid tumors, including NSCLC, breast cancer, head and neck squamous cell carcinoma, and others, are being enrolled in the study.⁴

REFERENCES:

1. Lift of partial clinical hold for BNT326/YL202. News release. BioNTech. August 19, 2024. Accessed August 19, 2024. https://tinyurl.com/389hshkj

2. United States Securities and Exchange Commission: Form 6-K. BioNTech. June 2024. Accessed August 19, 2024. https://tinyurl.com/y9wevncx

3. A study of YL202 in patients with locally advanced or metastatic non-small cell lung cancer and breast cancer. ClinicalTrials.gov. Updated June 21, 2024. Accessed August 19, 2024. https://clinicaltrials.gov/study/NCT05653752

4. A study of YL202 in selected patients with advanced solid tumors. ClinicalTrials.gov. Updated May 17, 2024. Accessed August 19, 2024. https://clinicaltrials.gov/study/NCT06107686