About 13% of all lung cancers in the United States are small cell lung cancer (SCLC), and approximately 87% are non–small cell lung cancer (NSCLC). Together, these lung cancers are the second most common cancer diagnosed in both men and women, excluding skin cancer. Usually a very aggressive disease, according to data from 2020, the cancer has a 5-year survival rate of only about 7%.
Results from a phase I study of zocilurtatug pelitecan, also known as ZL-1310, a DLL3-targeted antibody-drug conjugate, showed that the agent was safe and had clinical activity in patients with extensive-stage SCLC, including those whose cancer had metastasized to the brain. The data from the early clinical trial support further clinical development of ZL-1310 in this setting, according to the study authors. The study by Dy et al was presented during the AACR-NCI-EORTC International Conference on Molecular Targets.
Study Methodology
The researchers enrolled 115 patients with extensive-stage SCLC whose disease had progressed after treatment with platinum-based chemotherapy; of those patients, 37 (32%) had brain metastases. The patients had been heavily pretreated with available therapies. Ninety percent had been treated with PD-L1 inhibitors, and 44% with two or more prior therapies.
All of the patients received zocilurtatug pelitecan intravenously every 3 weeks until their disease progressed or they experienced unacceptable toxicity, with doses escalating from 0.8 mg/kg to 1.8 mg/kg. The treatment cycles ranged from 1 to 22, and among the patients evaluated, the median number of treatment cycles received was 6.
Results
The researchers found that zocilurtatug pelitecan demonstrated antitumor activity in the 102 patients evaluable at the data cutoff, with a confirmed objective response rate of 47% at all dose levels (additional 3% unconfirmed). The researchers observed 3 complete responses, 45 partial responses (additional 3 unconfirmed), and 39 patients with stable disease at all dose levels.
The 1.6-mg/kg patient cohort had the most objective responses to treatment, with 58% of the 19 patients with one prior line of therapy experiencing a confirmed partial response and an additional 10% with unconfirmed responses. The 32 patients with asymptomatic brain metastasis responded to treatment better than any other patient subgroup, with an objective response rate of 66%, composed of 1 complete response and 19 partial responses, and an additional unconfirmed response. Responses were also observed in patients with untreated brain metastasis at baseline (8 of 10).
The researchers also observed responses to treatment in the four patients whose tumors tested negative for DLL3 expression; in this group, the objective response rate was 50%. The 10 patients who had received prior treatments targeting DLL3 responded to zocilurtatug pelitecan with a 40% objective response rate, including one complete and three partial responses.
“ZL-1310 has a manageable safety profile, encouraging activity, and displayed meaningful improvements in patients with CNS [involvement], addressing a critical unmet need, including in those with asymptomatic, untreated brain metastases. These data support further clinical development of ZL-1310 in SCLC,” concluded the study authors.
Disclosure: Funding for this study was provided by Zai Lab. Grace K. Dy, MD, Director of Translational Research for Thoracic Medicine at the Roswell Park Comprehensive Cancer Center, and the presenter of this study, declares having consulted for and/or received honoraria from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Janssen, Novartis, Regeneron, and Whitehawk Therapeutics.
