LBA51 - Results from KEYNOTE-B49: A Phase 3, Randomized, Double-Blind Study of Pembrolizumab (Pembro) Vs Placebo (Pbo) Plus Chemotherapy (CT) in Participants (Pts) with HR+/HER2− Advanced Breast Cancer (ABC)

Presenter: Hope S. Rugo

Background

Once endocrine-based therapy (ET) has failed, patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer (ABC) have poor outcomes. The phase 3 KEYNOTE-B49 study tested whether adding pembrolizumab to chemotherapy (CT) benefits patients whose tumours express programmed death-ligand 1 (PD-L1).

Aim

To compare the efficacy and safety of pembrolizumab versus placebo, each combined with CT, in PD-L1–positive HR+/HER2− ABC.

Methods

• This randomised, double-blind phase 3 study enrolled patients with locally recurrent inoperable or metastatic HR+/HER2− ABC with a PD-L1 combined positive score (CPS) ≥1, who had received prior ET and were candidates for first-line CT.
• Patients were randomised to pembrolizumab 200 mg or placebo every 3 weeks (Q3W) for up to 35 cycles, plus CT (paclitaxel, nab-paclitaxel, liposomal doxorubicin or capecitabine).
• The primary endpoint was progression-free survival (PFS) per RECIST v1.1 by blinded independent central review (BICR) in patients with CPS ≥1; overall survival (OS) in this population was the key secondary endpoint. Multiplicity was controlled at α = 0.025 (1-sided).
• The sample size was reduced through a protocol amendment because of low PD-L1 prevalence.

Results

• 342 patients randomised: pembrolizumab + CT (n=171) vs placebo + CT (n=171); median age 57 years.
• Prior CDK4/6 inhibitor: 99.4% vs 98.8%.
• Primary PFS analysis (data cutoff 22 September 2025; median follow-up 29.1 months), PD-L1 CPS ≥1:
  • PFS events: 124/171 vs 139/171
  • Median PFS: 6.7 (95% CI 6.2–8.3) vs 6.0 (95% CI 4.2–8.1) months
  • HR 0.74 (95% CI 0.58–0.95; P=0.0089)
• PD-L1 CPS ≥10 subgroup:
  • Median PFS: 7.5 (95% CI 4.2–10.3) vs 4.4 (95% CI 4.0–8.3) months
  • HR 0.59 (95% CI 0.35–0.98)
• Final analysis (data cutoff 16 March 2026; median follow-up 34.9 months), PD-L1 CPS ≥1:
  • PFS benefit maintained: HR 0.74 (95% CI 0.58–0.95)
  • OS events: 126/171 vs 124/171
  • Median OS: 21.0 (95% CI 18.9–22.9) vs 22.2 (95% CI 17.6–26.3) months
  • OS HR 1.04 (95% CI 0.81–1.33; P=0.6185); no significant difference
• Safety:
  • Grade ≥3 treatment-related adverse events (TRAEs): 37.6% vs 32.7%
  • Discontinuation due to TRAEs: 11.2% vs 5.4%

Conclusion

In PD-L1 CPS ≥1 HR+/HER2− ABC, pembrolizumab added to chemotherapy produced a statistically significant PFS gain, equivalent to a 26% risk reduction, with manageable safety, although OS did not differ between arms at the final analysis. Among patients with CPS ≥10, PFS numerically favoured the pembrolizumab combination.

Reference

Rugo HS. Results from KEYNOTE-B49: A phase 3, randomized, double-blind study of pembrolizumab (pembro) vs placebo (pbo) plus chemotherapy (CT) in participants (pts) with HR+/HER2− advanced breast cancer (ABC), LBA51. Paper presented at: ESMO Congress 2026; October 23–27, 2026; Madrid, Spain

LBA14 - A Double-Blind Placebo Controlled Randomized Phase III Trial of Fulvestrant and Ipatasertib As Treatment for HER-2 Negative and Estrogen Receptor Positive (ER+) Metastatic Breast Cancer (MBC): Overall Survival Results of The CCTG/BCT MA.40/FINER Study

Presenter: Andrew D. Redfern

Background

The phase 3 MA.40/FINER study tested the pan-AKT inhibitor ipatasertib with fulvestrant in oestrogen receptor-positive (ER+)/HER2-negative metastatic breast cancer (MBC) immediately after progression on a CDK4/6 inhibitor (CDK4/6i) plus an aromatase inhibitor (AI). Both the primary endpoint, investigator-assessed PFS in the intention-to-treat (ITT) population, and the key secondary endpoint, PFS in the AKT pathway-altered cohort, showed statistically and clinically significant improvement.

Aim

To report the OS analysis of ipatasertib plus fulvestrant versus placebo plus fulvestrant.

Methods

• In this double-blind, placebo-controlled, randomised trial, pre-, peri- and postmenopausal women and men with ER+/HER2-negative MBC were randomised 1:1 to ipatasertib (400 mg orally daily, days 1–21) or placebo, each with fulvestrant (500 mg intramuscularly on days 1 and 15 of cycle 1, then day 1 of subsequent cycles).
• Randomisation was stratified by AKT pathway status (PIK3CA/AKT1/PTEN alteration on cell-free DNA [cfDNA] next-generation sequencing [NGS] vs wild-type/unknown) and by primary (<6 months on CDK4/6i) vs secondary (≥6 months) endocrine resistance.
• OS was a secondary endpoint.

Results

• 250 patients randomised: ipatasertib (n=125) vs placebo (n=125).
• Median follow-up: 35.0 months; 3.2% vs 2.4% of participants remained on protocol treatment.
• OS, ITT population:
  • Median OS: 26.68 (95% CI 21.42–30.78) vs 25.76 (95% CI 19.98–28.88) months
  • HR 0.97 (95% CI 0.70–1.33; p=0.83)
• OS, AKT pathway-altered cohort (exploratory):
  • Median OS: 23.66 (95% CI 18.53–28.65) vs 25.23 (95% CI 16.99–28.88) months
  • HR 1.14 (95% CI 0.72–1.80; p=0.58)
• No new safety signals emerged with longer follow-up.

Conclusion

Although ipatasertib plus fulvestrant had produced meaningful PFS gains in the second-line setting after CDK4/6i plus AI, the combination did not affect OS in either the overall population or the AKT pathway-altered cohort.

Reference

Redfern AD. A double-blind placebo controlled randomized phase III trial of fulvestrant and ipatasertib as treatment for HER-2 negative and estrogen receptor positive (ER+) metastatic breast cancer (MBC): Overall survival results of the CCTG/BCT MA.40/FINER study, LBA14. Paper presented at: ESMO Congress 2026; October 23–27, 2026; Madrid, Spain

LBA96 - First-Line (1L) Datopotamab Deruxtecan (Dato-Dxd) Vs Chemotherapy in Patients (Pts) with Locally Recurrent Inoperable or Metastatic Triple-Negative Breast Cancer (Mtnbc) for Whom Immunotherapy Was Not An Option: Exploratory Analysis of Pts with Brain Metastases in TROPION-Breast02

Presenter: Rebecca A. Dent

Background

Brain metastases (BMs) are frequent in triple-negative breast cancer (TNBC) and carry a poor prognosis. In TROPION-Breast02, first-line (1L) datopotamab deruxtecan (Dato-DXd) significantly improved OS (HR 0.79 [95.01% CI 0.64–0.98]) and BICR-assessed PFS (HR 0.57 [99% CI 0.44–0.73]), and improved confirmed objective response rate (ORR; 63% vs 29%), versus investigator’s choice of chemotherapy (ICC) in patients with locally recurrent inoperable or metastatic TNBC (mTNBC) for whom immunotherapy was not an option.

Aim

To describe efficacy outcomes with Dato-DXd versus ICC in patients with BMs at baseline.

Methods

• Patients were randomised 1:1 to Dato-DXd 6 mg/kg intravenously (IV) Q3W or ICC ((nab-)paclitaxel, capecitabine, eribulin mesylate or carboplatin).
• Patients with asymptomatic, stable BMs were eligible with or without prior central nervous system (CNS)-directed therapy; washout periods of 14 days after whole-brain radiation and 3 days after corticosteroids were required before cycle 1 day 1.
• Brain magnetic resonance imaging (MRI) or computed tomography (CT) was mandated at baseline, every 6 weeks for 48 weeks, then every 9 weeks until RECIST v1.1 progression.
• Exploratory analyses included BICR-assessed PFS, OS, confirmed ORR and intracranial response per modified RECIST (mRECIST) v1.1 in patients with previously treated or untreated BMs.

Results

• 644 patients enrolled; 61 had baseline BMs (31 previously treated, 30 untreated).
• All patients with baseline BMs (Dato-DXd n=36 vs ICC n=28):
  • Median PFS: 7.7 vs 3.5 months; HR 0.37 (95% CI 0.20–0.72)
  • Median OS: 13.5 vs 10.7 months; HR 0.55 (95% CI 0.29–1.05)
  • Extracranial confirmed ORR: 62.9% vs 19.2%
• Previously treated BMs (n=16 vs n=15):
  • Median PFS: 6.8 vs 3.5 months; HR 0.43 (95% CI 0.17–1.11)
  • Median OS: 19.3 vs 12.8 months; HR 0.77 (95% CI 0.28–2.08)
  • Extracranial confirmed ORR: 62.5% vs 33.3%
• Untreated BMs (n=20 vs n=13):
  • Median PFS: 7.7 vs 2.6 months; HR 0.29 (95% CI 0.12–0.76)
  • Median OS: 11.6 vs 9.1 months; HR 0.35 (95% CI 0.14–0.84)
  • Extracranial confirmed ORR: 63.2% vs 0%
• No baseline BMs (n=287 vs n=293):
  • Median PFS: 11.1 vs 5.6 months; HR 0.56 (95% CI 0.46–0.69)
  • Median OS: 23.7 vs 19.3 months; HR 0.80 (95% CI 0.64–1.00)
  • Extracranial confirmed ORR: 62.5% vs 30.2%
• Intracranial activity: a preliminary analysis showed intracranial objective responses with Dato-DXd, including one complete response; further intracranial data are to be presented.

 

Conclusion

First-line Dato-DXd improved efficacy over ICC regardless of whether asymptomatic, stable BMs were present at baseline, and whether or not they had received prior CNS-directed therapy. Early data also point to intracranial activity with Dato-DXd.

Reference

Dent RA. First-line (1L) datopotamab deruxtecan (Dato-DXd) vs chemotherapy in patients (pts) with locally recurrent inoperable or metastatic triple-negative breast cancer (mTNBC) for whom immunotherapy was not an option: Exploratory analysis of pts with brain metastases in TROPION-Breast02, LBA96. Paper presented at: ESMO Congress 2026; October 23–27, 2026; Madrid, Spain

LBA15 - Anbenitamab Plus Albumin-Bound Docetaxel in Patients (Pts) with HER2-Positive Advanced Breast Cancer (BC): A Randomized Phase III Study

Presenter: Binghe Xu

Background

The THP regimen (trastuzumab, pertuzumab and docetaxel) is an established first-line treatment for HER2-positive (HER2+) advanced breast cancer (BC), yet metastatic disease remains incurable and nearly half of patients progress within two years. Anbenitamab is a novel HER2-targeted bispecific antibody.

Aim

To report interim efficacy and safety of anbenitamab plus HB1801 (albumin-bound docetaxel) versus THP as first-line therapy in HER2+ advanced BC.

Methods

• This multicentre, randomised, open-label phase 3 trial enrolled patients with histologically confirmed HER2+ advanced BC and no prior chemotherapy or HER2-directed therapy for advanced disease.
• Patients were randomised 1:1 to anbenitamab plus HB1801 or THP, stratified by prior adjuvant/neoadjuvant therapy, hormone receptor status and visceral metastases.
• The primary endpoint was PFS by blinded independent review committee (BIRC); secondary endpoints included investigator-assessed PFS, ORR, duration of response (DoR), OS and safety.

 

Results

• 885 patients randomised: anbenitamab (n=445) vs THP (n=440).
• Interim analysis: data cutoff 30 April 2026; 401 PFS events.
• BIRC-assessed PFS:
  • Median PFS: not reached (95% CI 24.9–NE) vs 14.3 months (95% CI 12.4–16.4)
  • HR 0.46 (95% CI 0.37–0.56; p<0.0001)
• Investigator-assessed PFS: consistent improvement; HR 0.52 (95% CI 0.43–0.64)
• Confirmed ORR by BIRC: 87.6% vs 73.4%
• Median DoR: not reached (95% CI 27.0–NE) vs 16.6 months (95% CI 12.5–20.8)
• OS: immature, with a trend favouring anbenitamab.
• Safety:
  • Grade ≥3 TRAEs: 164 (36.9%) vs 111 (25.3%)
  • Most common: neutropenia, 13.1% vs 8.4%
  • Treatment-related deaths: 1 patient vs 2 patients
  • No new safety signals observed

Conclusion

As first-line therapy for HER2+ advanced BC, anbenitamab plus albumin-bound docetaxel delivered a significant and clinically meaningful PFS improvement over THP, with a favourable safety profile. The authors suggest this regimen may establish a new standard of care in this setting.

Reference

Xu B. Anbenitamab plus albumin-bound docetaxel in patients (pts) with HER2-positive advanced breast cancer (BC): A randomized phase III study, LBA15. Paper presented at: ESMO Congress 2026; October 23–27, 2026; Madrid, Spain

LBA73 - PACE-LUNG: A Multicenter, Single-Arm, Phase II Clinical Trial Evaluating The Efficacy of Additional Chemotherapy for Patients with Egfrm NSCLC with The Continued Presence of Plasma Ctdna Egfrm At Week 3 After Start of Osimertinib First-Line Treatment (AIO-TRK-0422/Ass)

Presenter: Martin Sebastian

Background

In advanced or metastatic non-small cell lung cancer (NSCLC) with common epidermal growth factor receptor mutations (EGFRm), persistence of EGFRm in circulating tumour DNA (ctDNA) after 3 weeks of osimertinib is associated with poor outcome, with a median PFS of 11.3 months in FLAURA. Adding chemotherapy (CTx) to osimertinib has improved PFS and OS at the cost of added toxicity, but no predictive biomarker exists to select patients for this approach.

Aim

To explore the feasibility and clinical utility of a ctDNA-guided treatment intensification strategy in EGFRm NSCLC.

Methods

• PACE-LUNG is an academic, multicentre, single-arm, investigator-initiated phase II trial.
• Patients with untreated advanced/metastatic NSCLC and persistent ctDNA EGFRm (Guardant360®) after 3 weeks of osimertinib monotherapy received 4 cycles of additional CTx, followed by osimertinib maintenance.
• The primary endpoint was investigator-assessed PFS per RECIST 1.1 from the start of CTx (PFS1). Secondary endpoints included PFS from the start of osimertinib (PFS0), OS from the start of CTx (OS1) and safety.

Results

• Screening (January 2022–September 2025): 255 patients screened; 74 (29%) had persistent ctDNA EGFRm after 3 weeks of osimertinib; 50 patients received additional CTx.
• Median age: 63 years (range 39–85); Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1 in 94% at CTx initiation.
• PFS1:
  • Median: 16.3 months (95% CI 10.8–18.9)
  • Progression-free and alive at 12 months: 57.8% (95% CI 42.0–70.6); at 24 months: 21.7% (95% CI 10.2–36.1)
• PFS0: median 17.8 months (95% CI 12.9–20.5)
• OS1:
  • Median: 29.2 months (95% CI 23.2–42.4)
  • Alive at 12 months: 87.4% (95% CI 74.1–94.2); at 24 months: 65.4% (95% CI 48.0–78.2)
• No new safety signals were observed.

Conclusion

Escalating to chemotherapy when ctDNA EGFRm persists early on osimertinib proved feasible and yielded PFS that compares favourably with historical data. The investigators propose using this strategy in future trials to support personalised therapy for EGFRm NSCLC.

Reference

Sebastian M. PACE-LUNG: A multicenter, single-arm, phase II clinical trial evaluating the efficacy of additional chemotherapy for patients with EGFRm NSCLC with the continued presence of plasma ctDNA EGFRm at week 3 after start of osimertinib first-line treatment (AIO-TRK-0422/ass), LBA73. Paper presented at: ESMO Congress 2026; October 23–27, 2026; Madrid, Spain

LBA74 - First-Line (1L) Trastuzumab Deruxtecan (T-Dxd) in Patients (Pts) with HER2-Mutant (HER2m) NSCLC: Patient-Reported Outcomes (Pros) from DESTINY-Lung04 (DL-04)

Presenter: Silvia Novello

Background

In DESTINY-Lung04 (DL-04), first-line trastuzumab deruxtecan (T-DXd) significantly improved PFS versus pembrolizumab plus chemotherapy in advanced/metastatic HER2-mutant (HER2m) NSCLC, with safety generally in line with the known profiles of each drug. Patient-reported outcomes (PROs) add the patient perspective on pulmonary symptoms and treatment tolerability.

Aim

To report PROs from DL-04, with a focus on pulmonary symptoms and patient-reported tolerability during treatment.

Methods

• DL-04 is a global, open-label phase 3 study in which patients with treatment-naïve HER2m (exon 19/20) NSCLC were randomised 1:1 to T-DXd 5.4 mg/kg or pembrolizumab 200 mg plus chemotherapy (cisplatin 75 mg/m² or carboplatin AUC 5, plus pemetrexed 500 mg/m²), all IV Q3W.
• Secondary PRO endpoints were time to deterioration (TTD) in cough, dyspnoea and chest pain on the NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ), and on-treatment tolerability, including physical function (PF) on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) PF subscale, overall side-effect bother on the Patient Global Impression of Treatment Tolerability (PGI-TT), and symptomatic adverse events (AEs) via EORTC and Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) item libraries.
• High side-effect bother (PGI-TT score 4 or 5, first 12 weeks only) was exploratory.

Results

• 454 patients randomised (data as of 9 June 2026).
• Median treatment duration: 12.3 months (range 0.7–44.8) with T-DXd vs 7.1 months (range 0.7–49.1) with pembrolizumab + chemotherapy.
• Median TTD in pulmonary symptoms (T-DXd vs pembrolizumab + chemotherapy):
  • Cough: 26.2 (95% CI 17.1–NC) vs 11.0 (95% CI 7.4–NC) months; HR 0.66 (95% CI 0.44–0.99)
  • Dyspnoea: 10.1 (95% CI 6.5–NC) vs 5.1 (95% CI 3.2–11.0) months; HR 0.77 (95% CI 0.54–1.09), favourable trend
  • Chest pain: NC (95% CI 11.5–NC) vs 14.3 (95% CI 8.3–NC) months; HR 0.80 (95% CI 0.54–1.18), favourable trend
• Physical function: the proportion with maintained/improved PF was similar between arms until Week 18 and generally higher with T-DXd from Week 20, including at end of treatment (EOT; 66.7% vs 57.7%).
• Side-effect bother: overall bother was similar across arms at most timepoints; patient-weeks with high side-effect bother were 13.4% in each arm.
• Symptomatic AE data are to be reported at the congress.

Conclusion

Patient-reported deterioration in pulmonary symptoms was delayed with T-DXd relative to pembrolizumab plus chemotherapy, while overall and high side-effect bother were broadly similar between arms; physical function was generally better maintained with T-DXd from Week 20 and at EOT. Together with the primary efficacy and safety results, these data support T-DXd as a new first-line option for HER2m NSCLC.

Reference

Novello S. First-line (1L) trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-mutant (HER2m) NSCLC: Patient-reported outcomes (PROs) from DESTINY-Lung04 (DL-04), LBA74. Paper presented at: ESMO Congress 2026; October 23–27, 2026; Madrid, Spain

LBA41 - Mocertatug Rezetecan (Mo-Rez) in Patients with Platinum-Resistant Ovarian Cancer (PROC): Updated Results with Longer Follow-Up from The Global BEHOLD-1 Study

Presenter: Vanda Salutari

Background

B7-H4 is a transmembrane protein widely expressed in gynaecological tumours but with low expression in normal tissue; its immunoregulatory and tumour-promoting functions make it a promising therapeutic target. Mocertatug rezetecan (Mo-Rez) is an investigational antibody–drug conjugate (ADC) composed of a humanised anti-B7-H4 IgG1 monoclonal antibody conjugated to a topoisomerase I (TOP1) inhibitor. Earlier BEHOLD-1 data in platinum-resistant ovarian cancer (PROC) and advanced/recurrent endometrial cancer led to selection of 5.8 mg/kg Q3W as the recommended dose for expansion.

Aim

To present updated efficacy and safety data in the PROC cohort after longer follow-up.

Methods

• BEHOLD-1 is a two-part, open-label phase 1 study.
• In phase 1b (dose selection), patients with PROC were randomised to Mo-Rez 2.8, 4.8 or 5.8 mg/kg Q3W.
• The primary endpoint is confirmed ORR by investigator per RECIST 1.1.

Results

• 136 patients with PROC randomised: 2.8 mg/kg (n=45), 4.8 mg/kg (n=46), 5.8 mg/kg (n=45); data cutoff 30 June 2026.
• Prior therapy: median 2 lines (range 1–5).
• Median follow-up: 13.4 months in each dose group.
• Confirmed ORR:
  • 2.8 mg/kg: 36% (n=16) [95% CI 21.9–51.2]
  • 4.8 mg/kg: 57% (n=26) [95% CI 41.1–71.1]
  • 5.8 mg/kg: 62% (n=28) [95% CI 46.5–76.2]
• Median DoR:
  • 2.8 mg/kg: 7.8 months [95% CI 4.4–NE]
  • 4.8 mg/kg: 6.9 months [95% CI 5.7–9.7]
  • 5.8 mg/kg: 12.2 months [95% CI 7.0–12.7]
• Median PFS:
  • 2.8 mg/kg: 5.6 months [95% CI 4.0–5.8]
  • 4.8 mg/kg: 8.3 months [95% CI 7.4–10.9]
  • 5.8 mg/kg: 11.1 months [95% CI 8.3–13.9]
• Safety (n=135 who received ≥1 dose):
  • Grade ≥3 TRAEs: 64 patients (47%) across all doses; 32 patients (71%) at 5.8 mg/kg
  • Discontinuation due to TRAEs: 3% overall; 2% at 5.8 mg/kg
• Efficacy by prespecified B7-H4 expression cut-offs is to be presented.

Conclusion

At the 5.8 mg/kg dose, Mo-Rez showed encouraging and durable activity in PROC, with median DoR of 12 months and median PFS of 11 months, alongside an acceptable safety profile. Enrolment into the 5.8 mg/kg expansion cohorts continues.

Reference

Salutari V. Mocertatug rezetecan (Mo-Rez) in patients with platinum-resistant ovarian cancer (PROC): Updated results with longer follow-up from the global BEHOLD-1 study, LBA41. Paper presented at: ESMO Congress 2026; October 23–27, 2026; Madrid, Spain

LBA52 - Personalized Neoantigen Vaccine Combined with Precision Critical Lesion Radiotherapy (CLERT) in Advanced Solid Tumors: Updated Results from The Inature Phase II Trial

Presenter: FengMing P. Kong

Background

Personalised neoantigen peptide vaccines (PPVax) have shown promise in the adjuvant setting but limited efficacy in advanced disease. The iNATURE study examined whether pairing PPVax with critical-lesion immuno-preserving radiotherapy (CLERT) could improve PFS in refractory solid tumours.

Aim

To evaluate PFS with PPVax versus placebo, each combined with CLERT, in metastatic solid tumours progressing after prior therapy.

Methods

• iNATURE (GCOG0028) is a randomised phase II trial in metastatic solid tumours progressing after ≥1 line of treatment.
• Immunogenic mutations were identified by whole-exome sequencing and validated by RNA sequencing; neoantigens were validated by 3 artificial intelligence (AI) algorithms.
• Individually manufactured PPVax (BXP-001) was given as 5 priming doses (month 1) plus 4 monthly boosters.
• Patients were stratified by tumour type and randomised 1:1 to PPVax or placebo; all received stereotactically designed CLERT targeting critical lesions.
• Neoantigen-specific immune responses were assessed by enzyme-linked immunospot (ELISpot) and enzyme-linked immunosorbent assay (ELISA); toxicity was graded per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, and quality of life (QoL) was recorded using the NIH/NCI Patient-Reported Outcomes Measurement Information System (PROMIS).

Results

• Screening: 114 patients screened for tumour genomic mutations; 106 had neoantigens; 40 were eligible and consented.
• 35 patients randomised: PPVax (n=16) vs placebo (n=19); 26 (74.3%) lung cancer, 4 (11.4%) colorectal cancer, 5 other solid tumours; median 3 prior lines of systemic therapy.
• PFS:
  • Median PFS: 10.3 months (95% CI 6.2–not reached) vs 3.1 months (95% CI 2.0–6.4); p=0.0045
  • HR 0.29 (95% CI 0.12–0.71; p=0.007)
  • No significant difference across cancer types (p=0.651)
• Immune responses with PPVax: neoantigen-specific T-cell responses in 83.3% of evaluable patients; antibody responses in 100%.
• Tumour shrinkage: 2/16 patients in the PPVax arm had >30% shrinkage of liver or mediastinal metastases.
• Safety and QoL: no grade ≥3 PPVax-related AEs in either arm; QoL did not change significantly in either arm.

Conclusion

Combined with CLERT, PPVax significantly prolonged PFS, by about 7 months, without serious toxicity in patients with solid tumours refractory to multiple lines of treatment. A multicentre validation study is underway.

Reference

Kong FP. Personalized neoantigen vaccine combined with precision critical lesion radiotherapy (CLERT) in advanced solid tumors: Updated results from the iNATURE phase II trial, LBA52. Paper presented at: ESMO Congress 2026; October 23–27, 2026; Madrid, Spain

LBA48 - Liver Function Trajectory and Post-Progression Outcomes in The Phase 3 EMERALD-3 Study of Tremelimumab (T) + Durvalumab (D) ± Lenvatinib (L) + Transarterial Chemoembolisation (TACE) in Participants (Pts) with Embolisation-Eligible Hepatocellular Carcinoma (eehcc)

Presenter: Masatoshi Kudo

Background

The phase 3 EMERALD-3 study met its primary endpoint, and OS trends favoured tremelimumab (T) plus durvalumab (D) (the STRIDE regimen), with or without lenvatinib (L), plus transarterial chemoembolisation (TACE) over TACE alone in embolisation-eligible hepatocellular carcinoma (eeHCC). Preserved liver function allows patients to receive subsequent treatment after progression.

Aim

To explore liver function trajectory and outcomes by baseline liver function in post-hoc analyses of EMERALD-3.

Methods

• Patients (≥18 years) with eeHCC were randomised 1:1:1 to STRIDE (T 300 mg + D 1500 mg on day 1; then D 1500 mg every 4 weeks) + L (8 or 12 mg once daily) + TACE, STRIDE + TACE, or TACE until 175 patients per arm were enrolled; randomisation then continued 1:1 until STRIDE + L + TACE and TACE reached ~275 patients per arm.
• Stratification factors were region, prior palliative embolisation and baseline tumour burden.
• The primary endpoint was PFS for STRIDE + L + TACE vs TACE; key secondary endpoints were OS for STRIDE + L + TACE vs TACE, and PFS and OS for STRIDE + TACE vs TACE. PFS on next-line therapy (PFS2) was a secondary endpoint.
• Outcomes were assessed by baseline albumin-bilirubin (ALBI) grade; data cutoff was 23 February 2026.

Results

• Liver function: in the safety analysis set (SAS), mean ALBI and Child-Pugh scores remained stable over the treatment period across baseline grades.
• OS, STRIDE + L + TACE vs TACE (full analysis set [FAS]):
  • ALBI grade 1: 44.6 months (95% CI 39.5–NC) vs 39.2 months (95% CI 34.7–NC); HR 0.86 (95% CI 0.60–1.22)
  • ALBI grade 2/3: 28.5 months (95% CI 20.7–34.3) vs 22.1 months (95% CI 17.4–33.3); HR 0.88 (95% CI 0.60–1.28)
• OS, STRIDE + TACE vs TACE (FAS):
  • ALBI grade 1: NC (95% CI 37.8–NC) vs 39.2 months (95% CI 28.0–NC); HR 0.57 (95% CI 0.36–0.90)
  • ALBI grade 2/3: 27.9 months (95% CI 17.8–NC) vs 20.4 months (95% CI 16.6–30.1); HR 0.81 (95% CI 0.52–1.26)
• PFS2 and time to next treatment (TTNT), ALBI grade 1:
  • STRIDE + L + TACE (n=188) vs TACE (n=183): PFS2 39.5 (95% CI 34.0–NC) vs 25.8 (95% CI 21.6–NC) months, HR 0.70 (95% CI 0.51–0.95); TTNT 21.1 (95% CI 18.5–27.3) vs 10.6 (95% CI 8.7–12.8) months, HR 0.56 (95% CI 0.43–0.72)
  • STRIDE + TACE (n=105) vs TACE* (n=111): PFS2 NC (95% CI 37.8–NC) vs 23.9 (95% CI 17.4–38.4) months, HR 0.53 (95% CI 0.36–0.79); TTNT 20.3 (95% CI 15.6–33.7) vs 9.2 (95% CI 7.2–11.3) months, HR 0.46 (95% CI 0.33–0.64)
• PFS2 and TTNT, ALBI grade 2/3:
  • STRIDE + L + TACE (n=105) vs TACE (n=109): PFS2 24.5 (95% CI 18.8–34.1) vs 17.4 (95% CI 14.6–25.2) months, HR 0.74 (95% CI 0.52–1.05); TTNT 14.0 (95% CI 10.8–20.4) vs 7.3 (95% CI 5.5–9.2) months, HR 0.57 (95% CI 0.41–0.77)
  • STRIDE + TACE (n=70) vs TACE* (n=64): PFS2 24.7 (95% CI 15.8–32.5) vs 17.1 (95% CI 13.3–22.1) months, HR 0.69 (95% CI 0.46–1.05); TTNT 13.4 (95% CI 8.4–17.6) vs 6.0 (95% CI 4.6–8.9) months, HR 0.55 (95% CI 0.38–0.80)
  • *TACE comparator drawn from the first 175 patients per arm
• Subsequent treatment use (ALBI grade 1 / grade 2/3): STRIDE + L + TACE 43% / 46%; STRIDE + TACE 50% / 53%; TACE 72% / 68%.
• Maximum grade 3/4 TRAEs (SAS), similar across baseline ALBI grades:
  • ALBI grade 1: STRIDE + L + TACE 115/185 (62%) vs TACE 32/181 (18%); STRIDE + TACE 49/105 (47%) vs TACE* 22/109 (20%)
  • ALBI grade 2/3: STRIDE + L + TACE 65/102 (64%) vs TACE 22/109 (20%); STRIDE + TACE 36/70 (51%) vs TACE* 17/64 (27%)

Conclusion

Across baseline ALBI grades, STRIDE-based regimens with or without lenvatinib plus TACE showed clinically relevant improvements in post-progression and survival outcomes compared with TACE, while liver function remained stable during treatment and safety was comparable. These exploratory findings support STRIDE-based therapy plus TACE as a potential new treatment option for eeHCC.

Reference

Kudo M. Liver function trajectory and post-progression outcomes in the phase 3 EMERALD-3 study of tremelimumab (T) + durvalumab (D) ± lenvatinib (L) + transarterial chemoembolisation (TACE) in participants (pts) with embolisation-eligible hepatocellular carcinoma (eeHCC), LBA48. Paper presented at: ESMO Congress 2026; October 23–27, 2026; Madrid, Spain

LBA16 - VIKTORIA-1: Updated Results of A Randomized, Open-Label, Phase 3 Study of Gedatolisib (Geda) + Fulvestrant (Fulv) ± Palbociclib (Palbo) Vs Standard of Care In Patients (Pts) with HR+/HER2- Advanced Breast Cancer (ABC) (Study 2)

Presenter: Barbara Pistilli

Background

Gedatolisib is a PI3K/mTOR inhibitor that blocks the PI3K/AKT/mTOR (PAM) pathway. The phase 3 VIKTORIA-1 trial enrolled patients with HR+/HER2− ABC into two studies by PIK3CA status (wild-type [wt] and mutant [MT]); both met their primary median PFS (mPFS) endpoint, leading to US Food and Drug Administration (FDA) approval in PIK3CA wt ABC.

 

Aim

To report updated results from Study 2 (PIK3CA MT), including subgroup efficacy and more detailed safety analyses.

Methods

• In this randomised, open-label phase 3 study, patients in Study 2 were randomised 3:3:1 to gedatolisib + palbociclib + fulvestrant (Arm D, n=155), alpelisib + fulvestrant (Arm E, n=155) or gedatolisib + fulvestrant (Arm F, n=52), all given in 28-day cycles.

Results

• Primary endpoint met: gedatolisib + palbociclib + fulvestrant significantly improved mPFS vs alpelisib + fulvestrant.
• Gedatolisib + palbociclib + fulvestrant (Arm D) vs alpelisib + fulvestrant (Arm E), mPFS:
  • Visceral metastases: 9.8 vs 5.6 months; HR 0.52 (95% CI 0.37–0.74)
  • No visceral metastases: 21.5 vs 9.2 months; HR 0.38 (95% CI 0.19–0.82)
  • Liver metastases: 9.1 vs 4.6 months; HR 0.47 (95% CI 0.31–0.70)
  • No liver metastases: 21.5 vs 9.1 months; HR 0.46 (95% CI 0.28–0.78)
• Gedatolisib + fulvestrant (Arm F) vs alpelisib + fulvestrant (Arm E), mPFS:
  • Visceral metastases: 11.3 vs 5.6 months; HR 0.53 (95% CI 0.33–0.85)
  • No visceral metastases: not reached vs 9.2 months; HR 0.40 (95% CI 0.13–1.31)
  • Liver metastases: 11.1 vs 4.6 months; HR 0.38 (95% CI 0.20–0.69)
  • No liver metastases: 11.5 vs 9.1 months; HR 0.71 (95% CI 0.37–1.39), numerical improvement
• Median DoR (including unconfirmed partial response per RECIST v1.1): Arm D 19.4 months (95% CI 11.1–25.1); Arm F 27.8 months (95% CI 9.2–NE); Arm E 7.5 months (95% CI 5.6–16.6).
• Treatment-emergent AEs (TEAEs; ≥1%) leading to gedatolisib withdrawal: 8 patients in Arm D (5.2%) and 2 patients in Arm F (3.8%):
  • Stomatitis: 1.3% (Arm D), 0% (Arm F)
  • Infusion-related reaction: 0% (Arm D), 1.9% (Arm F)
  • Pneumonitis: 0% (Arm D), 1.9% (Arm F)
• Stomatitis: most events occurred within the first 1–2 weeks of treatment, with <3% grade 3 stomatitis beyond cycle 2.
• Glucose: gedatolisib regimens had no clinically meaningful impact on fasting or non-fasting glucose levels.

Conclusion

In PIK3CA-mutant disease, gedatolisib-containing regimens extended mPFS over alpelisib plus fulvestrant in patients with and without visceral or liver metastases (with Arm F showing numerical rather than significant gains in some subgroups) and produced longer responses, while gedatolisib withdrawals were infrequent and glucose levels were not meaningfully affected. These data continue to support gedatolisib combinations for HR+/HER2− PIK3CA MT ABC.

Reference

Pistilli B. VIKTORIA-1: Updated results of a randomized, open-label, phase 3 study of gedatolisib (geda) + fulvestrant (fulv) ± palbociclib (palbo) vs standard of care in patients (pts) with HR+/HER2- advanced breast cancer (ABC) (Study 2), LBA16. Paper presented at: ESMO Congress 2026; October 23–27, 2026; Madrid, Spain

ESMO Congress 2026, 23 - 27 October 2026, Madrid