Melissa L. Johnson, MD, program director, Lung Cancer Research, lead, Solid Tumor Immune Effector Cellular Therapy Program, Sarah Cannon Research Institute, discusses the promise of DS-7300 in small cell lung cancer (SCLC) and other advanced solid tumors. 

During the 2021 ESMO Congress, findings from a phase 1/2 trial (NCT04145622) were presented. The study is evaluating the safety and initial efficacy of DS-7300. The antibody-drug conjugate (ADC) is directed toward B7 homologue 3 (B7-H3), which is a transmembrane protein overexpressed in several cancers, such as lung, prostate, esophageal, breast, and head and neck cancers. The ADC utilizes a topoisomerase I inhibitor payload as its mechanism of action. 

Among 70 patients who received various dosing levels of DS-7300, 15 derived a partial response with the agent. Responses were observed in patients with prostate cancer, SCLC, and esophageal squamous cell carcinoma, Johnson explains.

Notably, because B7-H3 is an immune checkpoint, knowledge generated in oncology with immunotherapy and other ADCs may inform the utility of DS-7300, Johnson concludes.

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Melissa L. Johnson, MD, discusses the promise of DS-7300 in small cell lung cancer and other advanced solid tumors.  



Dr. Johnson on the Promise of DS-7300 in SCLC and Other Advanced Solid Tumors 

Melissa L. Johnson, MD, director of Lung Cancer Research at Sarah Cannon Research Institute, Tennessee Oncology, discusses the clinical potential of AMG 757 in patients with small cell lung cancer (SCLC).

AMG 757 is just one example of a novel immune mechanism that is currently being explored in SCLC, according to Johnson. Bispecifics present a promising opportunity to advance immuno-oncology in SCLC, similar to what has been done in non–small cell lung cancer with the advent of immune checkpoint inhibitors, Johnson continues. There are opportunities beyond adding an immune checkpoint inhibitor to chemotherapy in this patient population, with several innovative strategies coming down the pipeline, Johnson concludes.

Melissa L. Johnson, MD, discusses the clinical potential of AMG 757 in patients with small cell lung cancer.

Dr. Johnson on the Clinical Potential of AMG 757 in SCLC

Melissa L. Johnson, MD, associate director, Lung Cancer Research, Sarah Cannon Research Institute, discusses the results of the phase 2 CITYSCAPE trial in PD-L1—positive non–small cell lung cancer (NSCLC).

In the CITYSCAPE trial, patients with chemotherapy-naïve locally advanced or metastatic NSCLC with a PD-L1 tumor proportion score (TPS) of at least 1% were randomized to the combination of tiragolumab and atezolizumab (Tecentriq; n = 67) versus placebo plus atezolizumab (n = 68). Coprimary end points were investigator-assessed objective response rate (ORR) and progression-free survival (PFS).

According to the primary analysis, tiragolumab/atezolizumab improved ORR and median PFS compared with tiragolumab/placebo. The ORR was 31.3% in the tiragolumab arm versus 16.2% in the placebo arm. The median PFS was 5.4 months and 3.6 months in the tiragolumab and placebo arms, respectively (HR, 0.57). Given these results, investigators continued to evaluate the safety and efficacy of the combination, says Johnson.

According to the updated analysis, the ORR was 37.3% versus 20.6% in the tiragolumab and placebo arms, respectively. Investigators also stratified patients according to PD-L1 tumor proportion score (TPS between 1% and 49% versus at least 50%). Patients with a PD-L1 TPS of at least 50% derived even more benefit from tiragolumab/atezolizumab with an ORR of 66% versus 24% with atezolizumab alone, concludes Johnson.

Melissa L. Johnson, MD, discusses the results of the phase 2 CITYSCAPE trial in PD-L1–positive non–small cell lung cancer (NSCLC).

Dr. Johnson on the Results of the CITYSCAPE Trial in PD-L1+ NSCLC

Melissa L. Johnson, MD, medical oncologist, Sarah Cannon Research Institute, discusses potential immunotherapy regimens for patients with lung cancer.

Pembrolizumab (Keytruda) is approved for patients in the frontline setting for tumors that express high PD-L1 expression, which is only seen in 30% of patients.

Chemotherapy plus immunotherapy or PD-L1 inhibitors in combination with other checkpoint inhibitors are currently being investigated to treat the remaining patients in the frontline setting.

PD-1 plus anti CTLA-4 has already been approved for the treatment of patients with metastatic melanoma. There are ongoing trials evaluating that strategy for patients with lung cancer, explains Johnson.

Melissa L. Johnson, MD

Articles

Dr. Johnson on the Promise of DS-7300 in SCLC and Other Advanced Solid Tumors

Dr. Johnson on the Clinical Potential of AMG 757 in SCLC

Dr. Johnson on the Results of the CITYSCAPE Trial in PD-L1+ NSCLC

Dr. Johnson on the Future of Immunotherapy in Lung Cancer