Lymph node metastasis in cancer progression: molecular mechanisms, clinical significance and therapeutic interventions

First Patient With Advanced Lung Cancer Dosed With Peluntamig Combo

The first patient was dosed in the SKYBRIDGE study assessing peluntamig with Tecentriq for advanced small cell lung cancer and neuroendocrine carcinomas.

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 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.

For more news on cancer updates, research and education, don't forget to subscribe to CURE®'s newsletters here.

Newsletter

Stay up to date on cancer updates, research and education

Making Every Inning Count: Eric's Game Plan Against Lung Cancer

Your browser is not supportedusatoday.Com

usatoday.Com wants to ensure the best experience for all of our readers, so we built our site to take advantage of the latest technology, making it faster and easier to use.

Unfortunately, your browser is not supported. Please download one of these browsers for the best experience on usatoday.Com

Participation In Lung Health Cohort Research Study Leads To Early Cancer Diagnosis

When a family member of a close friend, also in her 30s, was diagnosed with lung cancer, Cindy told her, "'You can ask me anything; I will be honest.' There are all these weird things that can happen, and you're not ready for it. It sucks. I hate that it happened me, and if I can help one person along the way, I will."

Cindy urges everyone to stay vigilant about their health and symptoms. "If you have lungs, you can get lung cancer. No one is immune to this. I have never smoked a cigarette. I grew up with asthma and I always prioritized my lung health. I tell people to listen to their own bodies—100%! If you have a nagging cough, go to the doctor. Hunt until you have an answer. Be persistent and find physicians you can trust."

And while she is always grateful that her cancer was caught early, her feelings about her diagnosis, and what she's been through ebb and flow, especially in the days and weeks before follow-up scans, every six months. 

"Personally, there are days when I still feel like it's not real, or sometimes when I'm talking about it, I feel like I'm telling somebody else's story," said Cindy. "At times, I feel unlucky to have received a lung cancer diagnosis at the age of 35."

On the positive side, "I have been introduced to so many fantastic people through the Lung Association who have also been impacted by lung cancer," she said.

The Lung Association is also "investing in incredible research and I'm hopeful that we're heading in the direction where more and more people can be like me; where they catch the cancer early and its more treatable, and people have a better chance," she said. "The passion is there."

The Lung Health Cohort Research Study is conducted through the Lung Association's Airways Clinical Research Centers (ACRC) Network, which is largest national non-profit clinical network dedicated to asthma and COPD research. The multi-site study is administered through the ACRC under the American Lung Association Research Institute. The Lung Health Cohort Research Study longitudinal study is funded by a $24.8 million grant from the National Heart, Lung, and Blood Institute, part of the National Institutes of Health.

The Lung Association also offers information, resources, including mentors and support groups, and many ways to get involved and help others. "Heck, just call the Lung Helpline if you have any lung health related questions or concerns, no matter how small."

"It's been a wild ride," Cindy said, "but it could have been a much worse one, for sure. I'm hopeful for the future of lung cancer for us all."

Learn more about the Lung Health Cohort Research Study at Lung.Org/lung-study and learn more about how you can help stand against cancer at LUNGFORCE.Org.

---