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WCLC 2023 Expert Perspectives

CE / CME

2023 World Conference on Lung Cancer: Expert Perspectives on Key Studies

Physician Assistants/Physician Associates: 1.50 AAPA Category 1 CME credits

Nurses: 1.50 Nursing contact hours

Physicians: maximum of 1.50 AMA PRA Category 1 Credits™

Pharmacists: 1.50 contact hours (0.15 CEUs)

Released: November 17, 2023

Expiration: November 16, 2024

Matthew Gubens
Matthew Gubens, MD, MS, FASCO
Helena Yu
Helena Yu, MD
CME/CE Information

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Subgroup Analysis of Patients With Refractory SCLC From Phase I/II Study Evaluating Novel ADC I-DXd in Refractory SCLC

Helena Yu, MD:
The first-line SoC for the treatment of adult patients with ES-SCLC is ICI therapy in combination with CT, either durvalumab with etoposide plus carboplatin or cisplatin or atezolizumab with etoposide plus carboplatin.55,68 Despite these advances after decades of no progress for this disease, there remains an unmet need for new treatment options for ES-SCLC, especially in the later-line settings.

 One potential option being studied is the B7-H3–directed ADC ifinatamab deruxtecan (I-DXd). B7-H3 (CD276) is a transmembrane immunoregulatory protein that is overexpressed in several cancers and linked to disease progression and shorter survival.81-83

 

Preliminary results of the phase I/II DS7300-A-J101 trial demonstrated antitumor activity for I-DXd with tolerable safety across pretreated advanced solid tumors, including ES-SCLC.84,85 The presentation at WCLC 2023 focused on the subgroup of patients with refractory ES-SCLC (n = 22) who received I-DXd.86 The primary endpoints of the dose-expansion part of the trial were ORR, DoR, DCR, PFS, and OS, with secondary endpoints of pharmacokinetics and immunogenicity.

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Phase I/II Study of I-DXd in Refractory SCLC: Baseline Characteristics

Helena Yu, MD:
The 22 patients with ES-SCLC in this early-phase trial were relatively heavily pretreated, having received a median of 2 prior lines of therapy. All had previously received platinum-based CT, and the majority had received IO (81.8%). There was a low incidence of brain metastases at baseline (9.1%).

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Phase I/II Study of I-DXd in Refractory SCLC: Antitumor Activity

Helena Yu, MD:
Although this cohort was relatively small, the majority of patients did see tumor shrinkage. With a median follow-up of 11.7 months, the ORR was 52.4%, with a median DoR of 5.9 months (95% CI: 2.8-7.5) and 2 patients remaining on treatment as of the data cutoff (January 31, 2023). These data are remarkable in the setting of refractory ES-SCLC.

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Phase I/II Study of I-DXd in Refractory SCLC: Survival

Helena Yu, MD:
The median PFS was 5.6 months, and median OS was 12.2 months.

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Phase I/II Study of I-DXd in Refractory SCLC: Safety Summary

Helena Yu, MD:
Regarding safety, grade ≥3 TEAEs were seen in 36.4% of patients and were associated with death in 1 patient (4.5%). The rate of TEAEs that led to treatment discontinuation was relatively high at 22.7%, so we will need to take a closer look at toxicities associated with I-DXd as more patients are treated.

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Phase I/II Study of I-DXd in Refractory SCLC: Adverse Events

Helena Yu, MD:
The most common TEAEs were nausea, fatigue, anemia, and vomiting. Again, this was a small number of patients with ES-SCLC, but 3 (13.6%) did develop grade 1/2 ILD, an AE we need to keep an eye out for with ADCs in our patients with lung cancer.

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Phase I/II Study of I-DXd in Refractory SCLC: Correlative Biomarker Analyses

Helena Yu, MD:
In an attempt to identify biomarkers that would predict efficacy of I-DXd, B7-H3 expression levels were assessed in the treated patients with ES-SCLC. Thus far, there does not seem to be a correlation between B7-H3 levels and response to I-DXd.

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Phase I/II Study of I-DXd in Refractory SCLC: Clinical Implications

Helena Yu, MD:
These are very early data, but I am excited anytime I see something show efficacy in ES-SCLC. Dr Gubens, what were your thoughts about these data?

Matthew Gubens, MD, MS:
I completely agree. There is such an unmet need for new therapies in refractory ES-SCLC that it was very exciting to see a glimmer of promising efficacy and manageable toxicity with I-DXd in this space.

I am also excited about other advances using ADCs, bispecific T-cell engagers, or even CAR T-cell therapy for the treatment of ES-SCLC. For example, there are several DLL3-CD3 bispecific T-cell engagers in development (tarlatamab, HPN328, and BI 764532).87-89 Although the DLL3-targeting ADC rovalpituzumab failed a few years ago, it was not because DLL3 was a poor target but rather that the cytotoxic payload was just too toxic. It is exciting to see the data for tarlatamab emerging and the development of drugs targeting DLL3 making a resurgence. It is an exciting time in the area of SCLC drug development.

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