ADCs Shine, Mixed Bag for Immunotherapy at ESMO 2026 Presidential Symposium III

Four late-breaking abstracts presented during Presidential Symposium III at the 2026 European Society for Medical Oncology (ESMO) Congress in Madrid reported phase 3 results across osteosarcoma, endometrial cancer, and advanced solid tumors. The session was chaired by Andrés Cervantes, MD, PhD, of Hospital Clínico Universitario de Valencia and INCLIVA in Spain, and Elizabeth Smyth, MB BCh BAO, MSc, MD, of Oxford University Hospitals NHS Foundation Trust in the United Kingdom.

Three of the trials, ARTEMIS-011, TroFuse-005, and KEYNOTE-C93, met their primary efficacy end points, with ARTEMIS-011 and KEYNOTE-C93 demonstrating significant improvements in progression-free survival (PFS) and TroFuse-005 demonstrating significant improvements in both PFS and overall survival (OS). The fourth, MOIO, was stopped early after reduced-frequency immune checkpoint inhibitor (ICI) treatment failed to demonstrate PFS noninferiority to standard-frequency dosing, with an unexpected OS imbalance favoring standard treatment. Together, the trials tested 2 antibody-drug conjugates (ADCs), a chemotherapy-free immunotherapy strategy, and a reduced-frequency ICI approach against standard comparators.

LBA9: Risvutatug Rezetecan Improves PFS vs Gemcitabine–Docetaxel in Heavily Pretreated R/R Osteosarcoma

Risvutatug rezetecan (Ris-Rez), a B7-H3–directed ADC with a topoisomerase I inhibitor payload, significantly improved PFS vs gemcitabine plus docetaxel in heavily pretreated patients with relapsed or refractory osteosarcoma, according to the primary results of the phase 3 ARTEMIS-011 study (NCT06935409) presented by Lu Xie, MD, of the Musculoskeletal Tumor Center at Peking University People’s Hospital in Beijing, China.¹

The open-label trial, conducted at 24 sites in China, randomized 122 patients 2:1 to Ris-Rez (12.0 mg/kg intravenously every 3 weeks; n = 80) or gemcitabine (1000 mg/m² on days 1 and 8) plus docetaxel (75 mg/m² on day 8) every 3 weeks (n = 42), with crossover to Ris-Rez permitted after progression. Eligible patients were aged 12 years or older, had progressed on or were intolerant to at least 2 prior lines of therapy, and had an ECOG performance status of 0 or 1. The primary end point was PFS by blinded independent central review (BICR). Median age was 21 to 22 years, about one-quarter of patients were adolescents, nearly all had lung metastases, and patients had received a median of 2.5 to 3 prior lines of therapy.

At a June 17, 2026, data cutoff and a median follow-up of 7.1 months, Ris-Rez reduced the risk of progression or death by 67% (HR, 0.33; 95% CI, 0.20-0.55; P < .0001). Median PFS was 5.5 months (95% CI, 4.1-7.4) vs 1.4 months (95% CI, 0.8-2.7), and 4-month PFS rates were 65% vs 33%. Benefit was consistent across prespecified subgroups, including patients aged 12 to younger than 18 years (HR, 0.26; 95% CI, 0.10-0.65), and investigator-assessed PFS was similar (HR, 0.30; 95% CI, 0.19-0.50).

The objective response rate (ORR) by BICR was 15% vs 2% and the disease control rate (DCR) was 76% vs 33%, with no complete responses; median duration of response (DOR) was 7.6 months with Ris-Rez. OS data were immature but numerically favored Ris-Rez (HR, 0.51; 95% CI, 0.21-1.23), with 10 deaths in each arm (13% vs 24%); 17 patients in the control arm crossed over.

Median treatment duration was 4.5 months with Ris-Rez vs approximately 1.5 months with gemcitabine plus docetaxel. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 93% vs 83% of patients and serious TRAEs in 64% vs 29%. TRAEs led to dose reduction in 71% vs 26% but to permanent discontinuation in only 4% vs 2%, and there were no fatal TRAEs. Hematologic toxicities were most common, including grade 3 or higher decreased white blood cell count (80%) and neutrophil count (79%) with Ris-Rez. Treatment-related interstitial lung disease occurred in 1 patient (grade 2).

“ARTEMIS-011 suggests that Ris-Rez is a promising new treatment option for patients with previously treated advanced relapsed or refractory osteosarcoma,” Xie concluded.

LBA10: Reduced-Frequency ICI Dosing Fails to Preserve Survival in Responding Patients With Advanced Cancer

Reducing ICI administration to once every 12 weeks in patients with advanced or metastatic solid tumors who were responding after 6 months of treatment was associated with an unexpected OS detriment vs standard dosing, prompting early termination of the phase 3 MOIO trial (NCT05078047), according to first interim analyses presented by Gwenaëlle Gravis, MD, of Institut Paoli-Calmettes in Marseille, France.²

The academic noninferiority trial randomized 340 patients at 36 centers 1:1 to continued standard ICI administration (n = 171) or ICI administration every 12 weeks (n = 169). Eligible adults had a complete or partial response after 6 months of an approved ICI-based regimen; patients with melanoma in complete response were excluded. PFS was the primary end point, assessed in co-primary modified intention-to-treat (mITT; n = 308) and randomized and treated (n = 339) populations, with noninferiority defined as an upper bound of the 90% CI for the HR of 1.30 or less. Lung cancer (30%), urothelial carcinoma (24%-26%), and renal cell carcinoma (19%) were the most common tumor types, about 75% of patients were receiving first-line therapy, and 81% to 83% were receiving an ICI alone.

At a December 1, 2025, data cutoff and a median follow-up of 18.6 months, 120 of 498 planned PFS events had occurred in the mITT population. Median PFS was 25.0 months (95% CI, 19.4-not estimable) with standard ICI vs 21.9 months (95% CI, 12.1-31.6) with reduced ICI (HR, 1.35; 96.16% CI, 0.90-2.04; 1-sided P = .0635), and the prespecified futility threshold was not crossed. However, deaths occurred in 10.5% vs 19.9% of patients, respectively (HR, 2.04; 95% CI, 1.08-3.85; 2-sided P = .0286), and results were similar in the randomized and treated population for PFS (HR, 1.28; 96.16% CI, 0.86-1.90) and OS (HR, 1.89; 95% CI, 1.03-3.48; P = .0400).

On April 10, 2026, the independent data monitoring committee recommended stopping enrollment in selected subgroups because of the OS imbalance, and on May 5, 2026, the steering committee concluded that accrual was no longer medically justified given the absence of a major safety advantage.

AE rates were similar between arms. Any-grade AEs occurred in 87.1% of patients receiving standard ICI vs 85.7% receiving reduced ICI, and grade 3 or 4 AEs in 29.8% vs 34.5%. Grade 3 or 4 TRAEs occurred in 10.5% vs 9.5%, and AEs led to discontinuation in 10.5% vs 8.9%. Patients in the reduced-ICI arm were advised to return to standard treatment, and follow-up and translational analyses are ongoing. The investigators noted limitations, including heterogeneity of the patient population and ICI regimens and short follow-up, and said neither noninferiority nor definitive inferiority could be formally concluded.

“These results cannot support implementation of the 12-week ICI in patients responding after initial ICI–based therapy. Further studies are needed to better define effective ICI de-intensification strategies,” Gravis said in her closing remarks.

LBA11: Sacituzumab Tirumotecan Improves Survival in Previously Treated Advanced or Recurrent Endometrial Cancer

Sacituzumab tirumotecan (sac-TMT), a TROP2-directed ADC, significantly improved PFS and OS vs treatment of physician’s choice (TPC) in patients with advanced or recurrent endometrial cancer previously treated with platinum-based chemotherapy and immunotherapy, according to the first interim analysis of the phase 3 TroFuse-005/ENGOT-en23/GOG-3095 trial (NCT06132958) presented by Domenica Lorusso, MD, PhD, of Humanitas University in Milan, Italy.³

The open-label trial randomized 776 patients at 242 sites in 31 countries and regions 1:1 to sac-TMT (4 mg/kg intravenously every 2 weeks; n = 386) or TPC with doxorubicin (60 mg/m² every 3 weeks) or paclitaxel (80 mg/m² on days 1, 8, and 15 of each 28-day cycle; n = 390). Eligible patients had prior platinum and anti–PD-1/PD-L1 exposure and no more than 3 prior lines of systemic therapy. PFS by BICR and OS were dual primary end points, and ORR was a key secondary end point. About 84% of patients had mismatch repair–proficient disease, 79.5% had medium-high TROP2 expression, and 37% to 39% had non-endometrioid histology. This was the final formal analysis for PFS, OS, and ORR.

At a March 23, 2026, data cutoff and a median follow-up of 14.0 months, sac-TMT reduced the risk of progression or death by 41% (HR, 0.59; 95% CI, 0.50-0.70; P < .0001). Median PFS was 7.2 months (95% CI, 5.6-7.6) vs 3.9 months (95% CI, 3.7-5.3), and 12-month PFS rates were 29.4% vs 12.4%. At a 67.5% information fraction, median OS was 19.0 months (95% CI, 16.1-not reached) vs 12.1 months (95% CI, 11.0-15.2) (HR, 0.68; 95% CI, 0.55-0.84; P = .0001), with 12-month OS rates of 63.4% vs 50.8%. ORR was 35.1% vs 17.3% (P < .00001), including complete responses in 6.1% vs 4.5%, and the ORR in non-endometrioid tumors was 41.3% vs 15.9%. DCR was 74.5% vs 57.3%, and median DOR was 11.1 vs 6.9 months.

Median treatment duration was 31 weeks with sac-TMT vs 15 weeks with TPC. Grade 3 or higher TRAEs occurred in 54.4% vs 41.4% of patients and serious TRAEs in 12.0% vs 13.6%. TRAEs led to dose interruption in 44.5% vs 21.5% and dose reduction in 29.2% vs 18.8% but to discontinuation in only 3.1% vs 4.9%, and 3 patients (0.8%) in each arm died of TRAEs. AEs of special interest with sac-TMT vs TPC included anemia (71.4% vs 46.6%), oral mucositis or stomatitis (57.0% vs 17.4%), ocular surface toxicity (30.5% vs 6.8%), and interstitial lung disease or pneumonitis (1.8% vs 0.5%). The incidence and severity of stomatitis decreased after mitigation measures including prophylactic mouthwash, and health-related quality of life was maintained with sac-TMT.

“For all these reasons, we believe that sac-TMT should be considered a new standard of care for patients who have failed chemo and immunotherapy and have very limited treatment options,” Lorusso concluded.

Watch: Domenica Lorusso, MD, PhD, discusses phase 3 findings on sacituzumab tirumotecan in advanced or recurrent endometrial cancer.

LBA12: First-Line Pembrolizumab Monotherapy Improves PFS vs Chemotherapy in dMMR Endometrial Cancer

First-line pembrolizumab (Keytruda) monotherapy significantly improved PFS vs carboplatin plus paclitaxel in patients with dMMR advanced or recurrent endometrial cancer, according to the prespecified interim analysis of the phase 3 KEYNOTE-C93/GOG-3064/ENGOT-en15 study (NCT05173987) presented by Brian M. Slomovitz, MD, of the GOG Foundation and Mount Sinai Medical Center in Miami Beach, Florida.

The open-label trial randomized 299 patients at 122 sites in 24 countries 1:1 to pembrolizumab (400 mg intravenously every 6 weeks for up to 18 cycles; n = 149) or carboplatin (AUC 5 or 6) plus paclitaxel (175 mg/m²) every 3 weeks for 6 cycles (n = 150). Patients in the chemotherapy arm could cross over to pembrolizumab after progression by BICR. Eligible patients had centrally confirmed dMMR disease, no prior systemic therapy, and an ECOG performance status of 0 or 1. PFS by BICR and OS were dual primary end points, and ORR was a key secondary end point. Median age was 61 to 62 years, 91.3% of patients had endometrioid histology, and 53% to 56% had recurrent disease.

At an April 24, 2026, data cutoff and a median follow-up of 36.7 months, pembrolizumab reduced the risk of progression or death by 43% (HR, 0.57; 95% CI, 0.42-0.79; P = .0002). Median PFS was 38.2 months (95% CI, 17.9-not reached) vs 8.4 months (95% CI, 6.8-10.4), and 36-month PFS rates were 52.8% vs 30.0%; the curves crossed at about 6 months, reflecting early disease control with chemotherapy and more durable control with pembrolizumab. OS numerically favored pembrolizumab but did not meet the prespecified significance criterion (HR, 0.77; 95% CI, 0.52-1.15; P = .1000), with 36-month OS rates of 70.7% vs 62.0%. Among patients in the chemotherapy arm with progression by BICR, 85.2% received subsequent immunotherapy, and supplementary analyses adjusting for this yielded OS HRs of 0.55 to 0.66. ORR was 64.1% vs 62.1%, with complete responses in 33.8% vs 26.2%, and median DOR was not reached vs 10.2 months.

Median treatment duration was 23.4 months with pembrolizumab vs 3.5 months with chemotherapy. TRAEs occurred in 71.1% vs 97.9% of patients, grade 3 or higher TRAEs in 18.1% vs 50.7%, and TRAEs leading to discontinuation in 9.4% vs 14.6%; TRAEs led to death in 2 patients (1.3%) vs 1 patient (0.7%). Immune-mediated AEs and infusion reactions occurred in 41.6% vs 17.4% (grade 3 or higher, 7.4% vs 3.5%), most commonly hypothyroidism. The presentation noted that the study did not compare pembrolizumab with the current standard of chemotherapy plus immunotherapy.

“KEYNOTE-C93 does not show that pembrolizumab alone is equivalent to chemotherapy and immunotherapy. What it does show is that for selected patients with dMMR disease, especially for those [for whom] avoiding chemotherapy is a priority, pembrolizumab monotherapy is a clinically relevant, chemotherapy-free, first-line option,” said Slomovitz.

Watch: Brian M. Slomovitz, MD, discusses the outcomes of the KEYNOTE-C93 trial of pembrolizumab for endometrial cancer.

REFERENCES

1. Xie L et al. Risvutatug rezetecan (Ris-Rez) versus gemcitabine and docetaxel (GD) in heavily pretreated patients (pts) with relapsed or refractory (R/R) osteosarcoma: primary results from the phase 3 ARTEMIS-011 study. Presented at: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract LBA9.

2. Gravis G et al. MOIO: interim analyses of a phase III randomized non inferiority trial assessing reduced frequency immune checkpoint inhibitors in responding patients with advanced/metastatic cancer. Presented at: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract LBA10.

3. Lorusso D et al. Sacituzumab tirumotecan in previously treated advanced or recurrent endometrial cancer: results from the phase 3 TroFuse-005/ENGOT-en23/GOG-3095 study. Presented at: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract LBA11.

4. Slomovitz B et al. KEYNOTE-C93/GOG-3064/ENGOT-en15: phase 3, randomized, open-label study of first-line (1L) pembrolizumab (pembro) vs carboplatin (C) + paclitaxel (P) in mismatch repair-deficient (dMMR) advanced or recurrent endometrial carcinoma (a/rEC). Presented at: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract LBA12.