vilastobart (XTX101) / Xilio Therap - LARVOL DELTA

Vilastobart (XTX101), a tumor-activated, Fc-enhanced anti–CTLA-4 monoclonal antibody, in combination with atezolizumab in patients with MSS CRC. (ASCO 2025) - P1/2 | "The combination of vilastobart, a novel tumor-activated, Fc-enhanced a-CTLA-4, and atezolizumab demonstrated initial evidence of anti-tumor activity in late line, metastatic MSS CRC where immune checkpoint blockade has historically been relatively ineffective. Vilastobart was observed to have a differentiated safety profile distinct from systemically active a-CTLA-4, consistent with tumor-selective activation."

Clinical • Combination therapy • IO biomarker • Colorectal Cancer • Oncology • CTLA4

EKLAVYA-HRD: Vilastobart+Retifanlimab in BRCA or PALB2 Deficient PC (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Massachusetts General Hospital

Checkpoint inhibition • New P2 trial • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • BRCA1 • BRCA2 • KRAS

XTX101 Monotherapy and XTX101 and Pembrolizumab Combination Therapy in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2; N=144; Recruiting; Sponsor: Xilio Development, Inc.; N=72 ➔ 144

Clinical • Combination therapy • Enrollment change • Monotherapy • Melanoma • Oncology • Solid Tumor

XTX101 Monotherapy and XTX101 and Atezolizumab Combination Therapy in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=96 | Recruiting | Sponsor: Xilio Development, Inc. | N=144 ➔ 96

Combination therapy • Enrollment change • Metastases • Monotherapy • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor

XTX101-01: Vilastobart (XTX101) Monotherapy and Vilastobart and Atezolizumab Combination Therapy in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=125 | Completed | Sponsor: Xilio Development, Inc. | Active, not recruiting ➔ Completed

First-in-human • Monotherapy • Trial completion • Colorectal Cancer • Lung Cancer • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • BRAF • EGFR • MSI

XTX101-01: Vilastobart (XTX101) Monotherapy and Vilastobart and Atezolizumab Combination Therapy in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=136 | Active, not recruiting | Sponsor: Xilio Development, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • First-in-human • Monotherapy • Colorectal Cancer • Lung Cancer • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • BRAF • EGFR • MSI

Molecular complete response to the RIN protocol (regorafenib, ipilimumab, and nivolumab) in a patient with advanced recurrent metastatic mismatch repair proficient/microsatellite stable (pMMR/MSS) rectal cancer. (PubMed, Ther Adv Med Oncol) - "Rectal cancer recurrence remains a major therapeutic challenge, particularly in patients unresponsive to conventional regimens. While previous studies have demonstrated limited benefit of immunotherapy in this tumor subtype, the present findings suggest an emerging therapeutic opportunity that warrants prospective evaluation to confirm efficacy, explore the mechanistic basis, and identify biomarkers predictive of durable response beyond the absence of liver metastases. More effective combinatorial regimens like zanzalintinib and atezolizumb (STELLAR-303) trial, as well as newer generation of CTLA-4 inhibitors like botensilimab, vilastobart, and muzastotug are showing more promise for patients with MSS colorectal cancers in particular who do not have liver metastases (NLM)."

IO biomarker • Journal • Mismatch repair • pMMR • Colorectal Adenocarcinoma • Colorectal Cancer • Embryonal Tumor • Immune Modulation • Immunology • Oncology • Rectal Adenocarcinoma • Rectal Cancer • Solid Tumor • CEACAM5 • KRAS

Phase 2 ctDNA Data Presented at SITC (GlobeNewswire) - "New data assessed plasma ctDNA using the Guardant360 Liquid (Infinity) assay and demonstrated the potential of ctDNA as a biomarker predictive of early response to treatment with vilastobart in combination with atezolizumab. Radiographic responses were accompanied by deep reductions in ctDNA (≥75% reduction), which generally occurred before radiographic responses, and ctDNA reductions were significantly associated with best overall response in the 23 patients with MSS mCRC without liver metastases who were evaluable for ctDNA and response correlation analysis as of a data cutoff date of May 12, 2025."

Biomarker • P2 data • Colorectal Cancer

Xilio Therapeutics Announces Late-Breaking Phase 2 Data for Vilastobart in Patients with MSS mCRC and High Plasma Tumor Mutational Burden at Society for Immunotherapy of Cancer (SITC) 40th Annual Meeting (GlobeNewswire) - "40% ORR in plasma TMB-high patients, consisting of six partial responses (PRs), with five confirmed PRs (with one confirmed after the data cutoff date) and one unconfirmed PR. In patients evaluable for plasma TMB status, 62.5% were TMB-high. All responders who were evaluable for plasma TMB status were TMB-high, and the correlation between plasma TMB status and response was statistically significant (p=0.05)."

Late-breaking abstract • P2 data • Colorectal Cancer

Plasma Tumor Mutational Burden (pTMB) Enriched for Response to Vilastobart in Combination with Atezolizumab in Patients with Microsatellite Stable (MSS) Metastatic Colorectal Cancer (mCRC) (SITC 2025) - P1/2 | "We previously reported vilastobart combined with atezolizumab (Tecentriq®) had a 26% overall response rate (ORR) in heavily pretreated patients with MSS mCRC without liver metastases (NLM), and a favorable safety profile consistent with tumor-activated design.1 High tumor mutational burden (TMB) is a biomarker predictive of response to immune checkpoint inhibitors (ICI) and is an approved tissue-based companion diagnostic for pembrolizumab in advanced solid tumors. Figures showing all pTMB-high (≥10 mut/Mb) NLM patients who had target lesion measurements available (12/15). pTMB=Plasma Tumor Mutation Burden; NLM=non liver metastases; PR=partial response"

Clinical • Combination therapy • IO biomarker • IO Companion diagnostic • Late-breaking abstract • Metastases • PD(L)-1 companion diagnostic • Tumor mutational burden • Colorectal Cancer • Oncology • Solid Tumor • TMB

ctDNA as a Potential Surrogate Biomarker for Response to Combination Vilastobart and Atezolizumab in Heavily Pretreated Microsatellite Stable (MSS) Metastatic Colorectal Cancer (mCRC) (NCT04896697) (SITC 2025) - P1/2 | "Larger, prospective studies are warranted to fully establish ctDNA as a surrogate endpoint.Trial Registration NCT04896697Ethics Approval This study was approved by Advarra Institutional Review Board, approval number Pro00054400. All study participants gave informed consent before taking part in the study."

Biomarker • Circulating tumor DNA • IO biomarker • Metastases • Colorectal Cancer • Oncology • Rectal Cancer • Solid Tumor

Xilio Therapeutics to Present Phase 2 Data for Vilastobart Highlighting Response Rate in Patients with MSS mCRC and High Plasma Tumor Mutational Burden as a Late-Breaking Presentation at SITC 40th Annual Meeting (GlobeNewswire) - "The Phase 2 data will highlight response rate for vilastobart in combination with atezolizumab in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) and high plasma tumor mutational burden."

Late-breaking abstract • P2 data • Colorectal Cancer

Xilio Therapeutics Announces Upcoming Presentations at the Society for Immunotherapy of Cancer (SITC) 40th Annual Meeting (GlobeNewswire) - "Xilio plans to present clinical data for vilastobart, a tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4, and efarindodekin alfa (XTX301), a tumor-activated IL-12, and plans to present preclinical data highlighting the company’s masked T cell engager programs."

P1/2 data • Preclinical • Colorectal Cancer

Vilastobart: tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4 (GlobeNewswire) - "Xilio anticipates reporting additional data from the Phase 2 trial in the first half of 2026."

P2 data • Colorectal Cancer

Xilio Therapeutics Announces Updated Phase 2 Data for Vilastobart, a Tumor-Activated Anti-CTLA-4, in Combination with Atezolizumab in Patients with Metastatic Microsatellite Stable Colorectal Cancer (GlobeNewswire) - P1/2 | N=136 | NCT04896697 | Sponsor: Xilio Development, Inc. | "26% preliminary objective response rate observed in heavily pre-treated patients with metastatic microsatellite stable colorectal cancer (MSS CRC) without liver metastases; Deep and durable responses ongoing for up to 37 weeks through the data cutoff, accompanied by substantial decreases in tumor biomarkers and improvements in clinical symptoms; MSS CRC patient with liver metastasis and previously reported confirmed partial response from Phase 1C (combination dose escalation) remains on treatment after more than 14 months; Combination continued to demonstrate differentiated safety and tolerability profile with low incidence of colitis and other immune-related adverse events."

P2 data • Colorectal Cancer

3553: A combination treatment of checkpoint inhibitors Vilastobart and atezolizumab shows promise in patients with advanced colorectal cancer (City of Hope) - P1/2 | N=136 | NCT04896697 | Sponsor: Xilio Development, Inc. | "In Phase 2 of a safety and tolerability clinical trial, metastatic colorectal cancer patients who have microsatellite stability (MSS) demonstrated initial evidence of anti-tumor activity when treated with the checkpoint inhibitors Vilastobart (XTX101) and atezolizumab....On the Phase 2 trial, 27% of patients without liver metastatic disease experienced a partial response, defined as more than 50% shrinkage of target lesions. Patients with tumor shrinkage had a significant decrease in circulating tumor DNA, further confirming the clinical efficacy of this combination. The combination was safe as it was associated with a low rate of severe immune-related complications. The safety was further demonstrated by a very low rate of treatment discontinuation."

P2 data • Colorectal Cancer

Xilio Therapeutics Announces Pipeline and Business Updates and First Quarter 2025 Financial Results (GlobeNewswire) - "R&D expenses were $8.3 million for the quarter ended March 31, 2025, compared to $10.4 million for the quarter ended March 31, 2024. The decrease was primarily driven by decreased clinical development activities for XTX202, a masked IL-2, as a result of discontinuing further investment in XTX202, decreased personnel-related costs due to lower headcount and decreased manufacturing costs for XTX301, partially offset by increased spending related to early stage programs and indirect research and development, increased clinical development activities for vilastobart and manufacturing activities for XTX501 in connection with IND-enabling studies."

Commercial • Colorectal Cancer • Oncology

Xilio Therapeutics to Present Updated Phase 2 Data for Vilastobart, a Tumor-Activated, Fc-Enhanced Anti-CTLA-4, in Combination with Atezolizumab in Patients with Microsatellite Stable Colorectal Cancer at the 2025 ASCO Annual Meeting (GlobeNewswire) - "Xilio Therapeutics...announced plans to present updated data from its ongoing Phase 2 clinical trial investigating vilastobart, a tumor-activated, Fc-enhanced anti-CTLA-4, in combination with atezolizumab (Tecentriq) in patients with metastatic microsatellite stable colorectal cancer (MSS CRC) at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting."

P2 data • Colorectal Cancer

Xilio Therapeutics Announces…Fourth Quarter and Full Year 2024 Financial Results (GlobeNewswire) - "R&D expenses were $8.8 million for the quarter ended December 31, 2024, compared to $11.7 million for the quarter ended December 31, 2023....The year-over-year decrease was primarily driven by decreased clinical development activities for XTX202, a masked IL-2, as a result of discontinuing further investment in XTX202, decreased spending related to early-stage programs and indirect research and development costs, decreased personnel-related costs and decreased manufacturing costs for XTX301, partially offset by increased clinical development activities for vilastobart and XTX301."

Commercial • Oncology • Solid Tumor

Pipeline and Business Updates: Vilastobart (GlobeNewswire) - "Xilio expects to report updated data from the Phase 2 clinical trial in the middle of 2025, including additional response assessments and follow-up....Based on the promising initial Phase 2 proof-of-concept data, Xilio plans to seek opportunities for partnering to accelerate and expand further development of vilastobart."

Commercial • P2 data • Colorectal Cancer

Clinical Studies Conducted at Florida Cancer Specialists & Research Institute Expanding Treatment Options and Improving Outcomes for Patients with Gastrointestinal and Genitourinary Cancers (PRNewswire) - "Clinical research conducted at Florida Cancer Specialists & Research Institute, LLC (FCS) is expanding treatment options and contributing to improved outcomes for patients diagnosed with gastrointestinal and genitourinary cancers. FCS research study results are featured at two global gatherings sponsored by the American Society of Clinical Oncology (ASCO)....At the ASCO 2025 Genitourinary Cancers Symposium, Cesar Augusto Perez, MD, as first author, will present results of a Phase I dose-escalation study of the next-generation nectin-4 targeting antibody–drug conjugate CRB-701 (SYS6002) in US and UK patients with urothelial cancer and other solid tumors."

Clinical data • P1 data • Preclinical • Colorectal Cancer • Gastric Cancer • Urothelial Cancer

Phase 1/2 study of XTX101, a tumor-activated, Fc-enhanced anti-CTLA-4 monoclonal antibody, in combination with atezolizumab in patients with advanced solid tumors and in MSS CRC. (ASCO-GI 2025) - P1/2 | "In Part 1C dose escalation, the combination of XTX101, a tumor-activated, Fc-enhanced aCTLA-4, and atezolizumab was generally well tolerated in pts with advanced solid tumors and demonstrated initial evidence of anti-tumor activity in cold tumors. These data support the initiation of an ongoing Phase 2 study evaluating the combination in pts with MSS CRC with and without liver metastases. 1."

Clinical • Combination therapy • IO biomarker • Metastases • P1/2 data • Ampulla of Vater Carcinoma • Colorectal Cancer • Esophageal Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • PD-L1

Xilio Therapeutics Announces Initial Phase 2 Data for Vilastobart (XTX101), a Tumor-Activated Anti-CTLA-4, in Combination with Atezolizumab in Patients with Metastatic Microsatellite Stable Colorectal Cancer (GlobeNewswire) - P1/2 | N=136 | NCT04896697 | Sponsor: Xilio Development, Inc. | "The data will be presented in a poster session (abstract #206) at the American Society of Clinical Oncology 2025 Gastrointestinal Cancer Symposium (ASCO GI)....As of a data cutoff date of January 13, 2025, 40 patients with metastatic MSS CRC had been treated with the combination of vilastobart....In patients without liver metastases, the preliminary objective response rate (ORR) was 27% with three partial responses (PRs), including two confirmed PRs. Responses were accompanied by decreases in levels of carcinoembryonic antigen (CEA) and circulating tumor DNA (ctDNA) as well as improvement in clinical symptoms.....In response-evaluable MSS CRC patients without liver metastases, investigators reported three PRs (two confirmed, one pending confirmation)....'We look forward to sharing additional Phase 2 data, including further follow-up, in patients with metastatic MSS CRC in the middle of this year'."

P2 data • Colorectal Cancer

Xilio Therapeutics to Present Initial Phase 2 Data for Vilastobart (XTX101), a Tumor-Activated Anti-CTLA-4, in Combination with Atezolizumab in Patients with Metastatic Microsatellite Stable Colorectal Cancer at ASCO GI (GlobeNewswire) - "Xilio Therapeutics, Inc...today announced plans to present initial data from its ongoing Phase 2 trial for vilastobart (XTX101)...in combination with atezolizumab (Tecentriq) in patients with metastatic microsatellite stable colorectal cancer (MSS CRC) at the ASCO Gastrointestinal (ASCO GI) Cancers Symposium in San Francisco, California from January 23-25, 2025."

P2 data • Colorectal Cancer

Phase 1 study of XTX101, a tumor-activated, Fc-enhanced anti-CTLA-4 monoclonal antibody, in combination with atezolizumab in patients with advanced solid tumors (SITC 2024) - P1/2 | "These data support the initiation of an ongoing Phase 2 study evaluating the combination in patients with MSS CRC with and without liver metastases. Ethics Approval This study obtained ethics approval though a central IRB (Advara IRB: Pro00057609) Participants gave informed consent before taking part in the study."

Clinical • Combination therapy • IO biomarker • Late-breaking abstract • Metastases • P1 data • Ampulla of Vater Carcinoma • Colorectal Cancer • Esophageal Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1