Jacob Sands, MD

In this segment, the panel discusses the emerging safety profile of next-generation CTLA-4-directed therapy in advanced squamous non-small cell lung cancer (NSCLC) and how toxicity findings should be interpreted alongside efficacy data.

In this segment, the panel reviews additional clinical data from the initial stage of the trial evaluating next-generation CTLA-4-directed therapy in advanced squamous non-small cell lung cancer (NSCLC).

In this segment, the panel examines early clinical data for a next-generation CTLA-4-directed therapy in patients with advanced squamous non-small cell lung cancer (NSCLC) whose disease has progressed following PD-L1 inhibitor and chemotherapy treatment.

In this segment, the panel explores the rationale for selectively targeting CTLA-4 within the tumor microenvironment in advanced squamous non-small cell lung cancer (NSCLC), with particular attention to intratumoral regulatory T cells (Tregs) and the potential to improve antitumor activity while limiting systemic toxicity.

In this segment, the panel discusses next-generation CTLA-4-directed therapies being engineered with the goal of improving selectivity and reducing the systemic toxicities associated with earlier CTLA-4 inhibitors in advanced squamous non-small cell lung cancer (NSCLC).

In this segment, the panel discusses the importance of proactive monitoring and multidisciplinary management of immune-related toxicities in patients with advanced squamous non-small cell lung cancer (NSCLC).

Drs Sen and Sands discuss lurbinectedin's place in the small cell lung cancer treatment paradigm.

In this segment, the panel discusses the toxicity profile of CTLA-4-directed therapies and how experience with immune-modulating treatments has influenced their use in advanced squamous non-small cell lung cancer (NSCLC).

In this segment, the panel explains the biological rationale for combining CTLA-4 and PD-1 inhibition in advanced squamous non-small cell lung cancer (NSCLC).

In this segment, the panel discusses the potential role of genomic testing and biomarker identification in advanced squamous non-small cell lung cancer (NSCLC), particularly as new therapeutic approaches emerge following immunotherapy.

In this segment, Dr. Christian Rolfo reviews emerging therapeutic approaches being investigated for patients with advanced squamous non-small cell lung cancer (NSCLC) following progression on immunotherapy.

Explore post-immunotherapy options for advanced squamous NSCLC, weighing docetaxel±ramucirumab, patient concerns, and why new trials matter.

When immunotherapy stops working in squamous NSCLC, clinicians weigh docetaxel±ramucirumab, weekly dosing, and clinical trials.

Dr. Sands discusses geographic and practice setting variations, noting lurbinectedin presents no administration challenges anywhere, whereas tarlatamab's rollout has been slower, initially concentrated in academic centers with clinical trial experience managing T-cell engagers and cytokine release syndrome.

Dr. Shields addresses choosing between atezolizumab-based (IMpower133) and durvalumab-based (CASPIAN) induction regimens, noting both demonstrate similar OS benefits (approximately 2.5-3 months) with real-world data showing general equipoise between agents.

Dr. Sands addresses the NCCN footnote stating lurbinectedin cannot be reused after relapse following maintenance use, comparing this to how progression on one PD-L1 inhibitor doesn't necessarily preclude using another.

Dr. Shields discusses trilaciclib, an FDA-approved supportive care medication from 2021 that prevents myelosuppression across red cells, white cells, and platelets, plus neutropenia.

Dr. Leal outlines current decision-making, noting lurbinectedin plus atezolizumab represents the approved standard frontline maintenance strategy for patients tolerating induction well, achieving stable disease or response, and motivated for treatment intensification.

Dr. Chiang addresses whether tarlatamab used in maintenance retains efficacy if used again after progression, acknowledging significant unknowns regarding resistance mechanisms for novel T-cell engager therapies compared to better-understood chemotherapy resistance.

Dr. Sands argues that successful second-line agents should move earlier in treatment sequencing, citing precedent from other oncology fields. With only 40% to 50% of patients with ES-SCLC receiving second-line therapy due to rapid disease progression, declining functional status, or brain metastases, moving effective agents like tarlatamab earlier addresses this attrition problem.

Dr. Shields addresses limitations of phase 1b single-arm studies, noting smaller patient numbers may introduce selection bias toward patients most likely to benefit from T-cell engager therapy targeting DLL3 and CD3. She emphasizes the importance of randomized phase 3 data for head-to-head comparisons, particularly given that DeLLphi-303's control arm involved immunotherapy alone, preventing cross-trial comparisons with IMforte's different control arm.

Dr. Sands discusses tarlatamab's unique mechanism as a bispecific T-cell engager linking DLL3 on tumor cells to CD3 on T cells, creating an antigen-directed immune response distinct from other therapeutic approaches. He characterizes the second-line DeLLphi-304 trial as establishing an entirely new paradigm, representing the only example of one drug outperforming others in SCLC's second-line setting across PFS, OS, tolerability, and symptom improvement.

Dr. Leal discusses practical logistics of lurbinectedin plus atezolizumab, administered together every 21 days. She incorporates maintenance discussions into initial treatment planning, particularly important for patients traveling long distances with caregivers. Most patients with ports prefer intravenous administration despite subcutaneous atezolizumab being an option with comparable efficacy, safety, and drug levels but shorter infusion time.

Dr. Shields confirms that NCCN guidelines now recommend lurbinectedin plus atezolizumab as preferred maintenance therapy following 4 cycles of chemotherapy and immunotherapy, with the specific footnote limiting this to patients with ECOG performance status 0 to 1 and no history of brain metastases. She strictly follows the brain metastasis exclusion criteria for treatment-naive patients but notes this restriction wasn't applied in second or third-line relapse settings.

Dr. Joshua Sabari introduces the program on evolving maintenance and sequencing strategies in extensive-stage small cell lung cancer (ES-SCLC), joined by Dr. Anne Chiang from Yale, Dr. Jacob Sands from Dana-Farber, Dr. Misty Shields from Indiana University, and Dr. Ticiana Leal from Emory University's Winship Cancer Institute.

Dr Sands discusses the rapidly evolving treatment landscape for SCLC.

In this final segment, Dr. Sands asks Dr. Cooper to discuss how subcutaneous administration of targeted therapies may influence clinical practice in EGFR-mutated non-small cell lung cancer.

In this segment, Dr. Sands asks the panel to discuss the emerging role of TROP2-directed antibody–drug conjugates in EGFR-mutated non-small cell lung cancer. Dr. Wakelee and Dr. Cooper explain that these agents are designed to target the TROP2 antigen on tumor cells and deliver a cytotoxic payload, enabling selective tumor cell killing.

In this segment, Dr. Sands asks Dr. Wakelee to discuss how emerging data on MET-driven resistance mechanisms are shaping second-line treatment decisions in EGFR-mutated non-small cell lung cancer.

In this case-based segment, Dr. Sands presents a patient with EGFR-mutated metastatic non-small cell lung cancer who has progressed after first-line combination therapy with an EGFR tyrosine kinase inhibitor and chemotherapy, now with new brain metastases.