First Patient With Advanced Lung Cancer Dosed With Peluntamig Combo

The first patient was dosed in the SKYBRIDGE study assessing peluntamig with Tecentriq for various cancers: © stock.adobe.com.

The first patient was dosed in the SKYBRIDGE clinical study evaluating peluntamig in combination with the anti-PD-L1 monoclonal antibody Tecentriq (atezolizumab) for extensive-stage small cell lung cancer, large cell neuroendocrine carcinoma of the lung or extrapulmonary neuroendocrine carcinomas, according to a news release from Phanes Therapeutics, Inc.

Phanes is conducting the study under a clinical supply agreement with Roche. Peluntamig, Phanes' first-in-class, IgG-like, bispecific antibody targeting DLL3 and CD47, has previously received two orphan drug designations from the U.S. Food and Drug Administration (FDA) for small cell lung cancer and neuroendocrine carcinoma. It has also previously received two fast track designations for extensive-stage small cell lung cancer following platinum chemotherapy with or without a checkpoint inhibitor, and for metastatic de novo or treatment-emergent neuroendocrine prostate cancer.

Delta-like protein 3 (DLL3) is part of the Notch signaling pathway, typically involved in early development. In cancer, DLL3 is often overexpressed on tumor cells, playing a role in tumor growth. CD47, also known as integrin-associated protein (IAP), is found on the surface of many normal cells, like red blood cells and platelets, but is also overexpressed in cancer cells. CD47 interacts with signal regulatory protein alpha (SIRPalpha) on immune cells, sending a "don’t eat me" signal that helps cancer cells evade destruction by the immune system. Targeting both DLL3 and CD47 may improve the immune system’s ability to recognize and attack cancer cells.

The SKYBRIDGE study is an ongoing, multi-center phase 1/2 clinical trial to assess the safety, tolerability, pharmacokinetics and early signs of efficacy of peluntamig in patients with advanced or treatment-resistant cancers that express DLL3. In addition to this U.S.-based study, a separate phase 1 trial is ongoing in China (CTR20242720), and a phase 2 trial has been approved for future launch in that country.

Several leading cancer centers across the United States are participating in the study, including the University of California San Francisco; Massachusetts General Hospital Cancer Center; Brigham and Women’s Hospital; Dana-Farber Cancer Institute; UNC Lineberger Comprehensive Cancer Center; University of Oklahoma Health Sciences Center; and the Cancer Therapy and Research Center at The University of Texas Health Science Center at San Antonio. The Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium is currently reviewing the protocol and may join the study as well.

Eligible patients for part A of the trial must have unresectable, advanced or metastatic disease confirmed by histology or cytology. Patients with mixed histology may enroll if at least 50% of the tumor consists of a small cell or neuroendocrine component. Participants must have either progressed on standard treatments — such as platinum-based chemotherapy, with or without checkpoint inhibitors — or be unable to tolerate available therapies. Those whose neuroendocrine cancer developed from non-small cell lung cancer are not eligible for this trial.

Large Cell Neuroendocrine Carcinoma of the Lung and Extrapulmonary Neuroendocrine Carcinomas

Large cell neuroendocrine carcinoma of the lung is a rare and aggressive form of lung cancer, exhibiting characteristics of both small-cell and non-small-cell lung cancers, according to the National Library of Medicine. The prognosis is generally poor, with a median overall survival of eight to 12 months.

Furthermore, according to the National Library of Medicine, extrapulmonary neuroendocrine carcinomas are a type of cancer that develops outside of the lungs, although the lung is the most common site for neuroendocrine carcinomas. Majority are found in the gastroenteropancreatic tract (about 37%), followed by the genitourinary tract (about 17%) and the gynecological tract (about 10%). These cancers are usually non-functioning, meaning they don't cause hormone-related symptoms. Instead, the symptoms often arise from a mix of site-specific issues and general signs of advanced cancer, such as weight loss and weakness.

For more information regarding the SKYBRIDGE trial, please visit www.clinicaltrials.gov using the identifier: NCT05652686.

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