Dr. Jared Weiss is the section chief of the Thoracic and Head/Neck Oncology at the UNC Lineberger Comprehensive Cancer Center, located in Chapel Hill, North Carolina.

Dr. Jared Weiss

Combining JNJ-1900 with Keytruda may improve distant control of lung cancer, explained by Dr. Jared Weiss.

Improving Distant Control in Lung Cancer With JNJ-1900 and Keytruda

Improving distant control of lung cancer is the most exciting potential benefit of combining JNJ-1900 with Keytruda (pembrolizumab), explained by Dr. Jared Weiss.

JNJ-1900 is a novel radioenhancer designed to be injected directly into tumors before hypofractionated radiation, helping maximize tumor destruction at that site while also potentially stimulating the immune system to fight cancer elsewhere in the body — an effect known as the abscopal effect.

Although this phenomenon has historically been rare, Weiss noted that real abscopal responses have been seen in metastatic disease with this approach, providing hope that the combination could improve distant control for patients with localized lung cancer.

Weiss is the section chief of Thoracic and Head/Neck Oncology at the UNC Lineberger Comprehensive Cancer Center, located in Chapel Hill, North Carolina. Weiss also serves as a professor of medicine in the Department of Medicine, Division of Oncology, at the UNC School of Medicine.

Are there any early indications of efficacy or biological activity in the current study cohort that might suggest potential for improving outcomes in patients that are being treated with this agent?

So the best indication that we might have efficacy in the localized setting is the efficacy that we've seen in the metastatic setting. My greatest fear when I treat a patient with a goal of cure with localized lung cancer is that they are going to recur with distant spread. Metastatic or distant spread is what causes most of the suffering and most of the death. And so when we look at the emergence of novel therapeutics for lung cancer, they're mostly oriented around improving that distant control.

Historically, that's been medicines. Medicines are nice because they get just about everywhere in the body. They go through the bloodstream. And this is a very novel, have-your-cake-and-eat-it-too type strategy in that you're doing something local. But what's really exciting about it for me — yes, it helps you fry the local thing, and that's nice — but it also does help with distant control. When you treat one spot with 1900 and then introduce [Keytruda], you have better control at distant spots. That effect, when you treat one area and you have efficacy elsewhere, is called the abscopal effect. Historically, it's something that had this huge ratio of how much radiation oncologists talked about it to how much it actually happened in the real world — probably 20 to one, at least. But there are real abscopal effects in metastatic disease with 1900, and that gives me a lot of hope that treatment in the localized context will improve distant control.

Transcript has been edited for clarity and conciseness.

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Dr. Jared Weiss explained that radiation for lung cancer may ease symptoms or aim to cure, with newer targeted forms potentially boosting immune responses.

Exploring Palliative and Curative Radiation for Lung Cancer 

Radiation for lung cancer is typically given in one of two settings: to relieve symptoms or with curative intent for unresectable disease, according to Dr. Jared Weiss 

For palliative care, the goal is comfort, such as treating painful bone metastases or easing breathing issues from airway compression. In contrast, curative radiation is used in cases like unresectable stage 3 lung cancer, typically delivered over several weeks to a large area of the chest for safety.

A newer form of radiation, called hypofractionated radiation or stereotactic body radiotherapy (sometimes by brand names like CyberKnife), involves giving a high dose to a small area in fewer sessions. 

 — designed to work with these shorter, targeted treatments. Unlike traditional chemotherapy-based radiation sensitizers, JNJ-1900 not only boosts the effect of radiation at the site but also helps trigger immune responses that may lead to further antitumor activity elsewhere in the body.

Traditional radiation for lung cancer is given in one of two contexts: either you have a spot that's a particular problem and you're giving the radiation to palliate, or you're giving it for unresectable disease with a goal of cure. For the former situation, a classic example might be a painful bony met (bone metastasis) where your goal of the radiation — you know you're not curing the person, you're not even extending survival — but you're trying to relieve pain at that site of the bony met. Another example might be a patient who has cough, trouble breathing from compression of a central airway, where your goal is to open that airway. Purely palliative — it's for comfort.

Whereas in the unresectable stage 3 disease, you're looking to cure people. JNJ-1900 is meant to work with hypofractionated radiation. Let's translate that into plainer English.

When you give curative intent radiation — when you're treating a big area in the chest — you're treating it over seven weeks, you break up that dose. Because you're treating such a large area, you need to do that for safety. So you're giving your total dose over six, six-plus weeks. That's traditional fractionation.

There's a new form of radiation, sometimes referred to by brand names like CyberKnife. Other names are stereotactic body radiotherapy or hypofractionated radiation, whatever you want to call it. That's the camp of radiation that 1900 is meant to work with — when you're giving a burst of radiation to a very small focal area in one or a very small number of sessions. And so you're not going to treat with JNJ-1900 a huge central tumor mass. You're going to treat a much smaller area.

Thus far, a lot of the data on it are really centered around its use more as an immune-stimulating agent than as a traditional radiation sensitizer like chemo, per se. It is a radiation sensitizer — it's a very potent one. That area that you deliver a small dose of hypofractionated radiation to, you're going to fry it. But what's truly special about 1900 isn't just that it's a radiation sensitizer — it's the downstream sequelae of that radiation sensitization for immune stimulation.

Articles

Radiation therapy for lung cancer is administered either for symptom relief or with curative intent in unresectable cases. Palliative radiation aims to alleviate discomfort from bone metastases or airway compression, while curative radiation targets unresectable stage 3 lung cancer over several weeks. Hypofractionated radiation, such as stereotactic body radiotherapy, delivers high doses to small areas in fewer sessions. JNJ-1900 enhances this approach by acting as a potent radiation sensitizer and stimulating immune responses, potentially leading to broader antitumor effects beyond the targeted site.

Dr. Jared Weiss

Improving Distant Control in Lung Cancer With JNJ-1900 and Keytruda

Exploring Palliative and Curative Radiation for Lung Cancer

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