Dr Das on the Landscape of Current and Emerging ADCs in SCLC

Millie Das, MD, clinical associate professor, medicine/oncology, member, Stanford Cancer Center, chief, oncology, Palo Alto VA, member, VA national Lung Cancer Working Group, Lung Cancer Precision Oncology Program, discusses the current landscape of new and emerging ADCs under investigation in small-cell lung cancer (SCLC), as well as highlights the phase 2 SWOG S1929 study (NCT04334941) in extensive-stage SCLC.

As one of the newest drug classes to emerge within the lung cancer space, there is significant interest in harnessing the efficacy of ADCs for patients with SCLC, Das begins. A number of ADCs are currently in development in this disease space, including the B7-H3-targeted agent ifinatamab deruxtecan (DS-7300), sacituzumab govitecan-hziy (Trodelvy), and the combination of atezolizumab (Tecentriq) plus talazoparib (Talzenna), Das reports.

The combination of atezolizumab plus talazoparib was recently evaluated in the phase 2 SWOG S1929 study in patients with extensive-stage SCLC who expressed Schlafen-11 (SLFN11), Das continues. Patients were randomly assigned to maintenance atezolizumab or maintenance atezolizumab plus talazoparib (AT) following treatment with frontline chemotherapy, she details. Notably, prior studies demonstrated that SLFN11 expression may be able to predict improved clinical outcomes with the PARP inhibitor veliparib (ABT-888) in combination with temozolomide.

Results from this trial were presented at the 2023 ASCO Annual Meeting, and showed that the addition of talazoparib to standard-of-care maintenance atezolizumab improved progression-free survival (PFS) in SLFN11-positive patients, Das states. The median PFS was 2.8 months with atezolizumab alone vs 4.2 months with the combination at a median follow-up of 5 months. Although minimal preliminary improvements in OS were observed, these data are immature.

However, overall response rates were numerically lower, at 12% with the combination and 16% with the monotherapy. Similarly, disease control rates were 69% and 59% with the monotherapy and combination, respectively.

Regarding safety, hematologic toxicity was slightly increased with the combination as expected. The most common adverse effect was grade 3 anemia. Additionally, treatment discontinuation due to toxicities did not increase in either arm.

The success of this trial demonstrated the viability and feasibility of prospective biomarker selected trials within SCLC, and suggested that these trials should pave the way forward, Das concludes.