FDA Places Partial Clinical Hold on Phase 1 Trial of YL202 in Advanced NSCLC and Breast Cancer


Key Takeaways

  • The FDA's partial clinical hold on YL202 is due to potential risks at higher doses, with five grade 5 adverse effects reported.
  • MediLink Therapeutics will review and share clinical and safety data with the FDA to address the hold.


The FDA has placed a partial clinical hold on the phase 1 YL202-INT-101-01 trial (NCT05653752) evaluating the antibody-drug conjugate (ADC) YL202 (BNT326) in heavily pretreated patients with advanced or metastatic EGFR-mutated non–small cell lung cancer (NSCLC) or hormone receptor (HR)–positive, HER2-negative breast cancer.1

In a filing with the United States Securities and Exchange Commission, BioNTech announced that it was informed by its partner, MediLink Therapeutics, that the partial clinical hold stems from the potential risk of illness or injuries at higher doses of YL202. Between YL202-INT-101-01 and the phase 2 YL202-CN-201-01 trial (NCT06107686), 5 patients being treated with the ADC have experienced grade 5 adverse effects.

To address the clinical hold, MediLink Therapeutics will review clinical and safety data; share available pharmacological data with the FDA; and provide additional information regarding safety findings from the YL202-INT-101-01 and YL202-CN-201-01 trials.

During the partial clinical hold, enrollment to YL202-INT-101-01 will be paused for patients in the United States.

YL202 is a novel ADC comprised of an anti-HER3 IgG1 monoclonal antibody that is connected via a tripeptide linked to 8 molecules of the novel topoisomerase I inhibitor YL0010014.2

YL202-INT-101-01 is an open-label, multicenter, first-in-human trial that had been enrolling patients at least 18 years of age with either histologically or cytologically confirmed locally advanced or metastatic NSCLC that was not amenable to curative surgery or radiation and harbored an EGFR exon 19 deletion or exon 21 L858R mutation; or histologically or cytologically confirmed unresectable locally advanced or metastatic, HR-positive, HER2-negative breast cancer. Patients with either tumor type needed to have documented disease progression on or after, or intolerance to, prior standard treatment regimens for locally advanced or metastatic disease.3

Other key inclusion criteria included an ECOG performance status of 0 to 2; adequate organ and bone marrow function; a life expectancy of at least 3 months; and at least 1 measurable tumor lesion per RECIST 1.1 criteria.

Patients were excluded if they were intolerant to prior treatment with a topoisomerase I inhibitor or an ADC containing a topoisomerase I inhibitor. Other exclusion criteria included major surgery within 4 weeks of first study dose or the expectation of major surgery during the study; prior allogeneic bone marrow transplantation or solid organ transplantation; any live vaccine given within 4 weeks of first study dose or the intention to receive a live vaccine during the study; a history of leptomeningeal carcinomatosis; uncontrolled or clinically significant cardiovascular disease; and a history of noninfectious interstitial lung disease (ILD) or pneumonitis requiring steroids, current ILD or pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.

Notably, patients with brain metastases or spinal cord compression were not allowed unless they were asymptomatic, or treated and stable after steroids and anticonvulsants for at least 2 weeks before study treatment.

All patients received YL202 once every 3 weeks at varying dose levels. During the initial dose, YL202 was infused for 90 minutes (± 10 minutes), and if no infusion-related reaction was observed, subsequent infusions were given for 60 minutes (± 10 minutes).

The incidence of dose-limiting toxicities during the first cycle and safety are the trial’s primary end points. Secondary end points consist of pharmacokinetics, objective response rate, disease control rate, best tumor response, duration of response, time to response, progression-free survival, and overall survival.

In the phase 2 YL202-CN-201-01 trial, the efficacy, safety, and pharmacokinetics of YL202 are being evaluated in select patients with advanced solid tumors, including NSCLC, breast cancer, head and neck squamous cell carcinoma, colorectal cancer, HER2-positive gastric cancer, cervical cancer, ovarian cancer, and others.4


  1. United States Securities and Exchange Commission: Form 6-K. BioNTech. June 2024. Accessed June 17, 2024.
  2. Cheng Y, Zhang X, Liu J, et al. YL202/BNT326, a HER3-targeted ADC, in patients with locally advanced or metastatic non-small cell lung cancer and breast cancer: preliminary results from a first-in-human phase I trial. J Clin Oncol. 2024;42(suppl 16):3034. doi:10.1200/JCO.2024.42.16_suppl.3034
  3. A study of YL202 in patients with locally advanced or metastatic non-small cell lung cancer and breast cancer. Updated July 6, 2023. Accessed June 17, 2024.
  4. A study of YL202 in selected patients with advanced solid tumors. Updated May 17, 2024. Accessed June 17, 2024.
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