Content - TROP2 TIGIT Lung Cancer | Decera Clinical Education

CE / CME

Expert Analysis: Clinical Advances Journal Club on Emerging TROP-2 and TIGIT Therapies in Lung Cancer

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit™

European Learners: 1.00 EBAC® CE Credit

Released: January 22, 2026

Expiration: July 21, 2026

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TROPiCS-03 (ES-SCLC Cohort): SG After Platinum-Based CT and Anti‒PD-1/PD-L1 Therapy

Alex Spira, MD, PhD, FASCO:
SCLC is a very complicated field at the moment, but there has been some study of TROP-2 and TIGIT agents in this disease.

TROPiCS-03 was a single-arm phase II study of SG in ES-SCLC after 1 prior line of platinum-based CT and an anti–PD-L1 agent. The primary endpoint was ORR by investigator.^37,38

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TROPiCS-03 (ES-SCLC Cohort): Efficacy

Alex Spira, MD, PhD, FASCO:
There was clear evidence of activity in this pretreated population with ORR of 41.9% and a reasonable median duration of response of 4.7 months.^37,38 Median OS (13.6 months) and PFS (4.4 months) are also impressive in these preliminary data.

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TROPiCS-03 (ES-SCLC Cohort): Safety

Alex Spira, MD, PhD, FASCO:
Safety results are as we have seen in the NSCLC studies, with incidence of diarrhea, neutropenia, and stomatitis.^37,38

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EVOKE-SCLC-04: SG vs Standard of Care in Previously Treated ES-SCLC

Alex Spira, MD, PhD, FASCO:
EVOKE-SCLC-04 is an ongoing phase III study randomizing patients with ES-SCLC with progression after 1 prior line of platinum-based CT with or without anti–PD-L1 therapy to SG and standard-of-care topotecan (NCT06801834).

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SKYSCRAPER-02: Atezolizumab + Carboplatin/Etoposide ± Tiragolumab in ES-SCLC

Alex Spira, MD, PhD, FASCO:
The phase III SKYSCRAPER-02 study of atezolizumab with carboplatin and etoposide, with tiragolumab or placebo in ES-SCLC failed to show a benefit in PFS or OS in the overall population and in most subgroups.³⁹ As I discussed previously, development of tiragolumab was discontinued.

Currently, there is no clear evidence of benefit with adding a TIGIT drug to standard-of-care treatment for an ES-SCLC.

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AdvanTIG-204: Ociperlimab (BGB-A1217) + Tislelizumab + cCRT in Untreated, Limited-Stage SCLC

Alex Spira, MD, PhD, FASCO:
Finally, the randomized phase II AdvanTIG-204 study tested the anti-TIGIT monoclonal antibody ociperlimab with tislelizumab and concurrent chemoradiotherapy (cCRT) vs tislelizumab plus cCRT vs cCRT alone in untreated limited-stage SCLC.^40,41 The 2 tislelizumab-containing arms also continued with maintenance therapy after 4 cycles of primary treatment. The study enrolled 126 patients with a primary endpoint of PFS by investigator.

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AdvanTIG-204: Efficacy

Alex Spira, MD, PhD, FASCO:
Median PFS of 12.6 months in the ociperlimab-containing arm suggests activity in limited-stage SCLC.^40,41 However, ociperlimab was also discontinued as a lung cancer treatment after poor early results from the phase III AdvanTIG-302 trial in NSCLC (NCT04746924).

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Key Takeaways

Alex Spira, MD, PhD, FASCO:
TROP-2 ADCs Dato-DXd and SG originally had negative phase III results for the treatment of NSCLC. However, retrospective analysis of Dato-DXd studies demonstrated positive outcomes for patients with EGFR mutations and led to the first FDA approval of a TROP-2 ADC in NSCLC.²³ Dato-DXd currently has a role in the treatment of patients with EGFR-mutated NSCLC after the FLAURA2 regimen of osimertinib and platinum-based CT. SG and sac-TMT have also shown promising results, and I look forward to seeing further study of these 3 drugs.

TIGIT agents have had less success in pulmonary cancer, although there are at least 2 still in development for NSCLC as single-agent therapy and in a variety of combinations. I hope to see positive results from further studies.

There are limited data for any of these agents in SCLC, but we may see more in the future.

Which of the following patients with SCLC would be a candidate for enrollment on the phase III EVOKE-SCLC-04 trial comparing SG with the current standard of care?

A.
Patients with previously untreated LS-SCLC
B.
Patients with previously untreated ES-SCLC
C.
Patients with ES-SCLC and 1 prior line of platinum-based chemotherapy (CT)
D.
Patients with ES-SCLC and ≥2 prior lines of therapy

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Expert Analysis: Clinical Advances Journal Club on Emerging TROP-2 and TIGIT Therapies in Lung Cancer

Benjamin Levy, MD, FASCO

Alex Spira, MD, PhD, FASCO

Activity

TROPiCS-03 (ES-SCLC Cohort): SG After Platinum-Based CT and Anti‒PD-1/PD-L1 Therapy

TROPiCS-03 (ES-SCLC Cohort): Efficacy

TROPiCS-03 (ES-SCLC Cohort): Safety

EVOKE-SCLC-04: SG vs Standard of Care in Previously Treated ES-SCLC

SKYSCRAPER-02: Atezolizumab + Carboplatin/Etoposide ± Tiragolumab in ES-SCLC

AdvanTIG-204: Ociperlimab (BGB-A1217) + Tislelizumab + cCRT in Untreated, Limited-Stage SCLC

AdvanTIG-204: Efficacy

Key Takeaways

Which of the following patients with SCLC would be a candidate for enrollment on the phase III EVOKE-SCLC-04 trial comparing SG with the current standard of care?