Precision at scale: Highlights in thoracic oncology from ASCO and ELCC 2026 (and beyond)
13 Oct 2026
By Kenneth G. Samala,* MD, FPSMO
(Note: This article, in partnership with the Philippine Society of Medical Oncology, appeared in the MIMS Oncology magazine, October–November 2026 issue.)
Thoracic oncology is at a tipping point this year, coming off from highlights from both ELCC in March and ASCO in June. Notable updates from these conferences support the transition from broad, single agent strategies to innovative combination therapies and expanded use of known drugs for metastatic disease to early-stage setting.
This paradigm shift can be summarized into three points: moving biomarker-driven targeted therapies into early curative-intent settings; shifting from single-agent therapies with dual-target bispecific drugs in first line advanced disease setting; and achieving long-term survival in driver-mutated non-small cell lung cancer (NSCLC), surpassing historical data.
Moving the needle: Breakthroughs in early-stage setting
One of the most anticipated data read outs from this year’s ASCO is from the Phase III LIBRETTO-432 trial (see Table for the description of trials mentioned in this article) which evaluated the use of selpercatinib, a highly selective oral RET inhibitor, in resected stage IB-IIIARET fusion-positive NSCLC. Selpercatinib demonstrated a statistically significant event-free survival (EFS) of 83% over placebo. Median EFS was not reached in the selpercatinib group vs. 31.8 months for placebo. No new safety signals were noted in this trial with transaminitis and hypertension as common and manageable side effects for the experimental arm.
The results of this trial impact how clinicians should be ordering biomarker panels in the early stage or adjuvant setting, expanding testing to incorporate RET fusions that were formerly held for advanced metastatic setting.
The bispecific revolution: Surpassing monotherapy standards
Pairing a single PD-1 or PD-L1 inhibitor with platinum doublet chemotherapy has long served as the standard of care for metastatic NSCLC lacking actionable mutations, but findings revealed at ASCO 2026 indicate that bispecific antibodies are reshaping this established paradigm.
Ivonescimab rewrites frontline squamous standards
The Phase III HARMONi-6 evaluated ivonescimab—a first-in-class bispecific antibody simultaneously targeting PD-1and Vascular endothelial growth factor (VEGF)—plus chemotherapy against the established anti-PD-1 agent tislelizumab plus identical chemotherapy in untreated advanced squamous NSCLC.
Ivonescimab plus chemotherapy achieved a median overall survival (OS) of 27.89 months compared to 23.69 months in the tislelizumab control arm (HR = 0.66, p = 0.0034). This marks the first randomized Phase III trial to show a head-to-head OS advantage of a bispecific platform over an active PD-1checkpoint inhibitor regimen in frontline NSCLC.
In addition, the survival benefit was observed regardless of PD-L1 status, even those with negative expression (<1%).
Next-gen dual PD-L1/VEGF platforms
Another support to the ever evolving role of bispecific molecules in NSCLC, the Phase I / II ROSETTA Lung-02 trial evaluated the role of pumitamig (a dualPD-L1/VEGF-A bispecific) paired with chemotherapy in first-line NSCLC, regardless of PD-L1 expression status. It demonstrated a very encouraging 70%objective response rate (ORR) and a100% disease control rate (DCR). An ongoing Phase III trial evaluating a lowerdose of pumitamig and chemotherapy vs. pembrolizumab and chemotherapy is currently underway.
Durability & precision in oncogene-driven subtypes
This year proved the further durability of tyrosine kinase inhibitors (TKIs) as highlighted by long term follow-up studies and novel use in different mutations.
The CROWN benchmark at seven years
The seven-year update of the landmark Phase III CROWN trial presented historic data in oncogene-driven lung cancer and set an unprecedented survival benchmark. At a median follow-up of 83 months, patients treated with frontline lorlatinib exhibited a 55% probability of remaining alive without disease progression at seven years, compared to just 3% with crizotinib in ALK+ NSCLC.
The investigator-assessed median PFS for lorlatinib has still not been reached (HR = 0.19). Moreover, lorlatinib demonstrated a 94% reduction in the risk of intracranial progression, with zero new central nervous system (CNS) progression events observed beyond 30 months of therapy, highlighting the ability of this targeted to effectively cross the blood brain barrier.
Targeting high-risk co-mutations & atypical variants
Several trials presented in both ASCO and ELCC focused on high-risk mutations like HER2, highlighted by the Beamion LUNG-1 trial, which showed that zongertinib achieved median PFS of 14.4 months, ORR of 76% and intracranial activity as well (59% intracranial ORR in active brain metastases).
The use of amivantamab + lazertinib as 1L treatment for atypical EGFR+ NSCLC (cohort C of CHRYSALIS-2) showed median OS of 41.0 months (55% three-year OS) and sustained intracranial durability.
Lastly, targeting EGFR in patients with advanced NSCLC harboring concurrentTP53 mutations with osimertinib + chemotherapy was established by the TOP trial. The Phase III trial showed that the combination arm doubled the median PFS to 34.0 months compared to 15.6 months with osimertinib alone. Likewise, ORR improved to 82.9% in the combination group versus 71.6% in the monotherapy arm. No new safety signals were noted and were aligned with earlier combination studies like FLAURA2.
Tackling primary resistance, hard-to-treat subtypes & extensive-stage small cell lung cancer (SCLC)
A persistent obstacle in thoracic oncology is primary resistance to immunotherapy, often linked to distinct co-mutational profiles like STK11, KEAP1, or KRAS, or specific alterations like EGFR exon 20 insertions.
Targeted solutions for exon 20 and co-mutational cold tumors
The WU-KONG28 study established oral sunvozertinib as a potentially better alternative to traditional platinum-based chemotherapy in advanced EGFR exon20 insertion mutation NSCLC. It reached its primary endpoint and demonstrated a statistically significant improvement in PFS (10.3 months vs. 7.5 months with chemotherapy). It also achieved a superior ORR of 58.9% compared to 31.1%in the chemotherapy arm.
Presence of co-mutations like STK11and KEAP1 poses a challenge for clinicians treating NSCLC. The TRITON trial evaluated if adding a dual immune checkpoint blockade (tremelimumab +durvalumab) to frontline chemotherapy could reverse primary resistance mechanisms to this group of patients. Early data demonstrated higher ORR over standard single-agent PD-1 combinations (48% vs. 33.3%), validating the potential of dual checkpoint inhibition in genetically cold tumor microenvironments.
Emerging option in relapsed SCLC
The DeLLphi-304 Trial evaluated the use of tarlatamab, a bispecific T-cell engager (BiTE) targeting Delta-like ligand3 (DLL3), against standard chemotherapy (such as topotecan or lurbinectedin) in relapsed SCLC. Tarlatamab demonstrated significant superiority in terms of median OS (13.6 months vs. 8.3months) and ORR (35% vs. 20%). This is a welcome development in the management of SCLC where options were limited for many years.
What’s on the horizon?
As the upcoming ESMO 2026 Congress in Madrid approaches, several notable readouts are expected to shape the treatment landscape of thoracic oncology:
• HARMONi-3 global expansion: Phase 3 data for ivonescimab plus chemotherapy in non-squamous NSCLC
• LAURA & MARIPOSA overall survival maturation: Updated mature OS and CNS control readouts evaluating consolidation osimertinib in stage III unresectable EGFR-mutated NSCLC (LAURA) and first-line amivantamab plus lazertinib (MARIPOSA).
• ADC sequencing protocols: Emerging clinical updates for TROP2 and HER3-targeted antibody drug conjugates like datopotamab deruxtecan and patritumab deruxtecan following disease progression on previous TKIs or chemo-immunotherapy.
*Clinical Associate Professor, UP College of Medicine; Division of Medical Oncology, Department of Medicine UP-Philippine General Hospital; email: kgsamala@up.edu.ph
Acronyms/abbreviations/symbols (not otherwise described/spelled out): ALK - anaplastic lymphoma kinase; ASCO 2026- 2026 American Society of Clinical Oncology Annual Meeting;CTLA-1 - cytotoxic T-lymphocyte-associated transcript1; EGFR - epidermal growth factor receptor; ELCC 2026 -European Lung Cancer Congress 2026; HER2 - human epidermal growth factor receptor 2; HR - hazard ratio; IO - immuno-oncology (a.k.a. immunotherapy); KEAP1 - Kelch-like ECH-associated protein 1; KRAS - protein arising from Kirsten rat sarcoma virus oncogene homologue; mOS - median overall survival; mPFS - median progression-free survival; ORR- overall response rate; OS - overall survival; p - probability value; PD-1 - programmed cell death protein 1; PD-L1 - programmed death-ligand 1; PFS - progression-free survival; RET - “rearranged during transfection” gene; STK11 - serine/threonine kinase 11; TP53 - tumor protein 53; TROP2 - trophoblast cell surface antigen 2
(Note: This article, in partnership with the Philippine Society of Medical Oncology, appeared in the MIMS Oncology magazine, October–November 2026 issue.)
Thoracic oncology is at a tipping point this year, coming off from highlights from both ELCC in March and ASCO in June. Notable updates from these conferences support the transition from broad, single agent strategies to innovative combination therapies and expanded use of known drugs for metastatic disease to early-stage setting.
This paradigm shift can be summarized into three points: moving biomarker-driven targeted therapies into early curative-intent settings; shifting from single-agent therapies with dual-target bispecific drugs in first line advanced disease setting; and achieving long-term survival in driver-mutated non-small cell lung cancer (NSCLC), surpassing historical data.
Moving the needle: Breakthroughs in early-stage setting
One of the most anticipated data read outs from this year’s ASCO is from the Phase III LIBRETTO-432 trial (see Table for the description of trials mentioned in this article) which evaluated the use of selpercatinib, a highly selective oral RET inhibitor, in resected stage IB-IIIARET fusion-positive NSCLC. Selpercatinib demonstrated a statistically significant event-free survival (EFS) of 83% over placebo. Median EFS was not reached in the selpercatinib group vs. 31.8 months for placebo. No new safety signals were noted in this trial with transaminitis and hypertension as common and manageable side effects for the experimental arm.
The results of this trial impact how clinicians should be ordering biomarker panels in the early stage or adjuvant setting, expanding testing to incorporate RET fusions that were formerly held for advanced metastatic setting.
The bispecific revolution: Surpassing monotherapy standards
Pairing a single PD-1 or PD-L1 inhibitor with platinum doublet chemotherapy has long served as the standard of care for metastatic NSCLC lacking actionable mutations, but findings revealed at ASCO 2026 indicate that bispecific antibodies are reshaping this established paradigm.
Ivonescimab rewrites frontline squamous standards
The Phase III HARMONi-6 evaluated ivonescimab—a first-in-class bispecific antibody simultaneously targeting PD-1and Vascular endothelial growth factor (VEGF)—plus chemotherapy against the established anti-PD-1 agent tislelizumab plus identical chemotherapy in untreated advanced squamous NSCLC.
Ivonescimab plus chemotherapy achieved a median overall survival (OS) of 27.89 months compared to 23.69 months in the tislelizumab control arm (HR = 0.66, p = 0.0034). This marks the first randomized Phase III trial to show a head-to-head OS advantage of a bispecific platform over an active PD-1checkpoint inhibitor regimen in frontline NSCLC.
In addition, the survival benefit was observed regardless of PD-L1 status, even those with negative expression (<1%).
Next-gen dual PD-L1/VEGF platforms
Another support to the ever evolving role of bispecific molecules in NSCLC, the Phase I / II ROSETTA Lung-02 trial evaluated the role of pumitamig (a dualPD-L1/VEGF-A bispecific) paired with chemotherapy in first-line NSCLC, regardless of PD-L1 expression status. It demonstrated a very encouraging 70%objective response rate (ORR) and a100% disease control rate (DCR). An ongoing Phase III trial evaluating a lowerdose of pumitamig and chemotherapy vs. pembrolizumab and chemotherapy is currently underway.
Durability & precision in oncogene-driven subtypes
This year proved the further durability of tyrosine kinase inhibitors (TKIs) as highlighted by long term follow-up studies and novel use in different mutations.
The CROWN benchmark at seven years
The seven-year update of the landmark Phase III CROWN trial presented historic data in oncogene-driven lung cancer and set an unprecedented survival benchmark. At a median follow-up of 83 months, patients treated with frontline lorlatinib exhibited a 55% probability of remaining alive without disease progression at seven years, compared to just 3% with crizotinib in ALK+ NSCLC.
The investigator-assessed median PFS for lorlatinib has still not been reached (HR = 0.19). Moreover, lorlatinib demonstrated a 94% reduction in the risk of intracranial progression, with zero new central nervous system (CNS) progression events observed beyond 30 months of therapy, highlighting the ability of this targeted to effectively cross the blood brain barrier.
Targeting high-risk co-mutations & atypical variants
Several trials presented in both ASCO and ELCC focused on high-risk mutations like HER2, highlighted by the Beamion LUNG-1 trial, which showed that zongertinib achieved median PFS of 14.4 months, ORR of 76% and intracranial activity as well (59% intracranial ORR in active brain metastases).
The use of amivantamab + lazertinib as 1L treatment for atypical EGFR+ NSCLC (cohort C of CHRYSALIS-2) showed median OS of 41.0 months (55% three-year OS) and sustained intracranial durability.
Lastly, targeting EGFR in patients with advanced NSCLC harboring concurrentTP53 mutations with osimertinib + chemotherapy was established by the TOP trial. The Phase III trial showed that the combination arm doubled the median PFS to 34.0 months compared to 15.6 months with osimertinib alone. Likewise, ORR improved to 82.9% in the combination group versus 71.6% in the monotherapy arm. No new safety signals were noted and were aligned with earlier combination studies like FLAURA2.
Tackling primary resistance, hard-to-treat subtypes & extensive-stage small cell lung cancer (SCLC)
A persistent obstacle in thoracic oncology is primary resistance to immunotherapy, often linked to distinct co-mutational profiles like STK11, KEAP1, or KRAS, or specific alterations like EGFR exon 20 insertions.
Targeted solutions for exon 20 and co-mutational cold tumors
The WU-KONG28 study established oral sunvozertinib as a potentially better alternative to traditional platinum-based chemotherapy in advanced EGFR exon20 insertion mutation NSCLC. It reached its primary endpoint and demonstrated a statistically significant improvement in PFS (10.3 months vs. 7.5 months with chemotherapy). It also achieved a superior ORR of 58.9% compared to 31.1%in the chemotherapy arm.
Presence of co-mutations like STK11and KEAP1 poses a challenge for clinicians treating NSCLC. The TRITON trial evaluated if adding a dual immune checkpoint blockade (tremelimumab +durvalumab) to frontline chemotherapy could reverse primary resistance mechanisms to this group of patients. Early data demonstrated higher ORR over standard single-agent PD-1 combinations (48% vs. 33.3%), validating the potential of dual checkpoint inhibition in genetically cold tumor microenvironments.
Emerging option in relapsed SCLC
The DeLLphi-304 Trial evaluated the use of tarlatamab, a bispecific T-cell engager (BiTE) targeting Delta-like ligand3 (DLL3), against standard chemotherapy (such as topotecan or lurbinectedin) in relapsed SCLC. Tarlatamab demonstrated significant superiority in terms of median OS (13.6 months vs. 8.3months) and ORR (35% vs. 20%). This is a welcome development in the management of SCLC where options were limited for many years.
What’s on the horizon?
As the upcoming ESMO 2026 Congress in Madrid approaches, several notable readouts are expected to shape the treatment landscape of thoracic oncology:
• HARMONi-3 global expansion: Phase 3 data for ivonescimab plus chemotherapy in non-squamous NSCLC
• LAURA & MARIPOSA overall survival maturation: Updated mature OS and CNS control readouts evaluating consolidation osimertinib in stage III unresectable EGFR-mutated NSCLC (LAURA) and first-line amivantamab plus lazertinib (MARIPOSA).
• ADC sequencing protocols: Emerging clinical updates for TROP2 and HER3-targeted antibody drug conjugates like datopotamab deruxtecan and patritumab deruxtecan following disease progression on previous TKIs or chemo-immunotherapy.
*Clinical Associate Professor, UP College of Medicine; Division of Medical Oncology, Department of Medicine UP-Philippine General Hospital; email: kgsamala@up.edu.ph
Acronyms/abbreviations/symbols (not otherwise described/spelled out): ALK - anaplastic lymphoma kinase; ASCO 2026- 2026 American Society of Clinical Oncology Annual Meeting;CTLA-1 - cytotoxic T-lymphocyte-associated transcript1; EGFR - epidermal growth factor receptor; ELCC 2026 -European Lung Cancer Congress 2026; HER2 - human epidermal growth factor receptor 2; HR - hazard ratio; IO - immuno-oncology (a.k.a. immunotherapy); KEAP1 - Kelch-like ECH-associated protein 1; KRAS - protein arising from Kirsten rat sarcoma virus oncogene homologue; mOS - median overall survival; mPFS - median progression-free survival; ORR- overall response rate; OS - overall survival; p - probability value; PD-1 - programmed cell death protein 1; PD-L1 - programmed death-ligand 1; PFS - progression-free survival; RET - “rearranged during transfection” gene; STK11 - serine/threonine kinase 11; TP53 - tumor protein 53; TROP2 - trophoblast cell surface antigen 2