Beyond Checkpoint Blockade in SCLC: Emerging Antigen Targets and Treatment Strategies Across Disease Stages

Clinical Evidence on Emerging Antigen-Directed Strategies in ES-SCLC

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Dr. Leal:
Hello, this is CE with GLC, and I'm Dr. Ticiana Leal. Today, I'll review clinical evidence on emerging antigen-directed strategies in the treatment of extensive-stage small cell lung cancer.

First, I'd like to highlight the phase 1/2 trial CA001-030, which is a trial of BMS-986012 plus nivolumab in relapsed/refractory small cell lung cancer.

Fucosyl-GM1 is a glycosphingolipid expressed predominantly on lung cancers and limited on normal tissue. BMS-986012 is a non-fucosylated human IgG1 antibody that binds selectively to Fuc-GM1.

What we saw is the combination had a promising efficacy with an overall response rate of 38%. We saw a median duration of response of 26.4 months, median PFS of 2.1 months, and importantly, promising median overall survival of 18.7 months.

Overall in this study, we saw that the combination had a manageable safety profile, with low-grade pruritus as the most common treatment-related adverse event. This supporting further evaluation of this combination in the frontline setting.

The next study I'd like to highlight is the randomized phase 2 trial of CA001-050, which was a trial of frontline nivolumab plus chemotherapy plus/minus BMS in extensive-stage small cell lung cancer.

This study included patients with treatment-naive extensive-stage small cell lung cancer, and they were randomized 1:1 to induction with BMS plus nivolumab plus chemotherapy, followed by maintenance of the combination of BMS plus nivolumab versus nivolumab plus chemotherapy, followed by nivolumab maintenance.

This study was reported out at ESMO 2024, demonstrating here similar PFS between the 2 arms, with a median PFS of 5.2 months with the combination of nivo plus chemo versus 5.8 months with the combination of BMS plus nivolumab.

With the overall survival endpoint, what we saw was a numerical improvement of the overall survival going from 11.4 months with nivo plus chemo versus 15.6 months with BMS plus nivolumab plus chemotherapy, showing a very promising median overall survival, including at the 12-month overall survival rate of 67% with the experimental combination versus 48% with nivolumab plus chemotherapy. And although this did not meet statistical significance, given the promising median overall survival in the frontline setting and overall the tolerability of BMS plus nivolumab plus chemotherapy, this is moving forward and is currently being investigated in a randomized phase 3 trial.

Next, I'd like to highlight other strategies that are moving to the frontline in the investigational space. This is the phase 1b DeLLphi-303 trial, which had several frontline cohorts. I'll highlight here the frontline cohort including patients with platinum etoposide plus an anti-PD-L1, and then combining this with tarlatamab.

Tarlatamab is a T-cell engager that targets DLL3 and is now being investigated in this study. And what we saw in the frontline cohort of first-line chemotherapy plus immunotherapy plus tarlatamab is that this combination showed a safety profile that was consistent with what you'd expect from tarlatamab plus the experience that we've had with chemoimmunotherapy.

With regards to the overall efficacy endpoints in this first-line cohort, what we saw was promising activity with regards of the combination of tarlatamab plus chemotherapy and immunotherapy, which included both atezolizumab and durvalumab, with a 12-month overall survival rate of 80.6%.

I'd also like to highlight the experience with I-DXd. I-DXd is a B7-H3 antibody-drug conjugate with a topo I inhibitor payload.

Here, what you're seeing is now the efficacy of IDeate-Lung01 with I-DXd in previously treated patients. As you can see here, overall very promising activity of I-DXd, with a confirmed overall response rate of 48%.

The most common treatment-related adverse events noted here were grade 1 and 2 in nature, as noted here in this slide, in 10% or greater of patients, was nausea and myelosuppression.

Thanks very much for listening. I hope this brief overview will be useful in your practice.

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Overview
This online educational activity examines next-generation therapeutic approaches for small cell lung cancer (SCLC) beyond traditional checkpoint inhibition. The program reviews the biologic rationale for targeting antigens such as fucosyl-GM1, DLL3, and B7-H3, highlighting diverse immune effector strategies, including novel antibody combinations, bispecific T-cell engagers, and antibody-drug conjugates. Faculty discuss emerging clinical evidence for investigational approaches across both extensive-stage and limited-stage disease settings. Emphasis is placed on how disease stage, prior treatment exposure, mechanism of action, and evolving trial data can inform treatment selection, clinical trial referral, and future integration of antigen-directed therapies into SCLC care.
Commercial Support
This activity is supported by an independent educational grant from Bristol Myers Squibb.
Disclosure of Relevant Financial Relationships
In accordance with the ACCME Standards for Integrity and Independence, Global Learning Collaborative requires all faculty and planners to disclose financial relationships with ineligible companies. All relevant financial relationships have been reviewed and mitigated to ensure that the content is free from commercial bias.

The following faculty and planners have disclosed relevant financial relationships with ineligible companies in the past 24 months.

Faculty:
Ticiana Leal, MD
Director, Thoracic Medical Oncology
Emory University
Atlanta, GA

Consulting Fees: AbbVie Inc., AstraZeneca, BeOne, Bayer, Boehringer Ingelheim Pharmaceuticals, Inc., Catalyst, Daiichi Sankyo, Inc., Gilead Sciences, Inc., J&J, Merck, Novocure, Nuvation Bio, Verastem
Other: DSMB: OncoC4
Research:Daiichi Sankyo, Inc.

Neal Ready, MD, PhD
Professor
Duke Cancer Center
Durham, NC
Consulting Fees: BMS
Research: BMS

Reviewers/Planners/Authors:
- Cindy Davidson has no relevant relationships to disclose.
- Bing-E Xu, PhD, has no relevant relationships to disclose.
- Brian P. McDonough, MD, FAAFP, has no relevant relationships to disclose.
Learning Objectives
Upon completion of this activity, learners should be better able to:
- Distinguish the mechanisms of action, immune effector strategies, and combination rationale of emerging antigen-directed approaches in small cell lung cancer (SCLC)
- Evaluate emerging evidence for investigational antigen-directed regimens in SCLC to determine how disease stage, prior therapy, and mechanism of action should inform treatment choice and trial referral
Target Audience
This activity has been designed to meet the educational needs of oncologists and APPs as well as all other physicians, physician assistants, nurse practitioners, nurses, pharmacists, and healthcare professionals involved in managing patients with small cell lung cancer.
Accreditation and Credit Designation Statements
In support of improving patient care, Global Learning Collaborative (GLC) is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC) to provide continuing education for the healthcare team. 

Global Learning Collaborative (GLC) designates this enduring-activity for a maximum of 0.50 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Global Learning Collaborative (GLC) designates this activity for 0.50 nursing contact hour(s). Nurses should claim only the credit commensurate with the extent of their participation in the activity.

Global Learning Collaborative (GLC) has been authorized by the American Academy of Physician Associates (AAPA) to award AAPA Category 1 CME credit for activities planned in accordance with AAPA CME Criteria. This activity is designated for 0.50 AAPA Category 1 CME credit(s). Approval is valid until July 27, 2027. PAs should claim only the credit commensurate with the extent of their participation in the activity.

Global Learning Collaborative (GLC) designates this activity for a maximum of 0.50 contact hour(s)/0.05 CEUs of pharmacy continuing education credit.

The Universal Activity Number (UAN) for this program is JA0006235-0000-26-092-H01-P. This learning activity is competence-based. Upon successful completion of the activity, continuing education credit will be electronically submitted to the National Association of Boards of Pharmacy (NABP). Pharmacists with questions may contact NABP Customer Service at custserv@nabp.net.
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Global Learning Collaborative (GLC) designs and executes continuing education rooted in evidence-based medicine, clinical need, knowledge gap analysis, and careful consideration of learner feedback. Our mission is to serve as an inventive and relevant resource for clinical content and educational interventions across a broad spectrum of specialties. GLC’s methodology is founded on a commitment to continuing medical education and the innovative assessment of its effects on clinical practice. Our goal is clear—to develop and deliver the best education in the most impactful manner and to verify its results with progressive outcomes research.
Disclaimer
The views and opinions expressed in this educational activity are those of the faculty and do not necessarily represent the views of GLC. This presentation is not intended to define an exclusive course of patient management; the participant should use his/her clinical judgment, knowledge, experience, and diagnostic skills in applying or adopting for professional use any of the information provided herein. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients’ conditions and contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. Links to other sites may be provided as additional sources of information.

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System Requirements
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Publication Dates
Release Date: 07/27/2026
Expiration Date: 07/27/2027