WCLC 2023 | Dr. Johnson：Antibody Drug Conjugate (ADC) targeting B7-H3 shows efficient and durable efficacy in patients with refractory SCLC
Editor's note: The 2023 World Conference on Lung Cancer (WCLC), organized by the International Association for the Study of Lung Cancer (IASLC), was held from September 9 to 12 in Singapore. Dr. Melissa L. Johnson of Northwestern University Feinberg School of Medicine reported a significant study on antibody-drug couplings for the treatment of small cell lung cancer (SCLC) in the Oral Presentation Session (Abstract No. OA05.05), and Oncology Frontier invited Dr. Johnson for an interview at the conference. This article is organised for our readers' benefit.
Oncology Frontier: I-DXd demonstrated robust and durable efficacy in patients with heavily pretreated SCLC. Can you explain to us possible reasons why there is no correlation between best overall response and B7-H3 intensity ?
Dr. Johnson: We have looked at B7-H3 expression and tried to make an association with efficacy in this trial. It is important to remember that all patients expressed some amount of B7-H3, so I think a little bit may be enough. It may not be about the more B7-H3 expression you have, the better the response a particular tumor is able to have.
Oncology Frontier: Oncology Frontier:Could you tell us why you chose B7-H3 as the target for refractory SCLC ?
Dr. Johnson: This report today was 22 patients with small cell lung cancer who were part of dose escalation in a larger trial. Actually, there were ten different tumor types that we looked at, including prostate cancer, squamous lung cancer, squamous head and neck, and squamous esophageal cancer, among others. The reason this is important is because we found that B7-H3 was high enough in all of those patients to ask the question whether they would respond to a B7-H3-directed antibody drug conjugate (ADC). We chose the small cell lung cancer patients because we knew B7-H3 expression was high, but we looked across a number of tumor types and found good responses.
Oncology Frontier: What are the important advances in ADCs that have been reported?
Dr. Johnson: Antibody drug conjugates (ADCs) are the talk of this meeting. I have only been here for a day, and I think I saw in three sessions today, presentations about ADCs. Some of the new data being presented at this conference is moving those antibody drug conjugates up into the frontline and actually replacing chemotherapy with the antibody drug conjugate in combination with the immune therapy. This is the first time we are actually seeing results with as high as 80% of patients in the TROPION-Lung04 trial (carboplatin, durvalumab and datopotamab deruxtecan (Dato-DXd)) being treated. This is very interesting, and makes us need more data. The cohorts of patients that were reported today are small, so we need more experience to understand if it is the right thing to do to move those ADCs into the frontline.
Oncology Frontier: What other recent developments in refractory SCLC that interest you ? What advice would you give to patients with refractory SCLC ?
Dr. Johnson: Our patients with small cell lung cancer are treated with chemotherapy and checkpoint inhibitors, but of course, patients dont do very well once you stop the chemotherapy and continue with their immunotherapy. Another drug I am excited about is the DLL3 CD3 bispecifics like tarlatamab made by Amgen and others. Harpoon has one, and Roche has one. Boehringer Ingelheim has one. These drugs also seem to evoke an immune response in small cell lung cancer that is very different and better than checkpoint inhibitors. Ask your doctor about clinical trials. There is a lot to be hopeful for in the treatment of small cell lung cancer, and we have to continue trying new therapies.