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
Xilio Therapeutics (Nasdaq: XLO) announced initial Phase 2 data for vilastobart (XTX101) combined with atezolizumab in treating metastatic microsatellite stable colorectal cancer (MSS CRC). The trial showed a 27% preliminary response rate in patients without liver metastases, with three partial responses including two confirmed ones.
Key findings include decreased levels of carcinoembryonic antigen (CEA) and circulating tumor DNA (ctDNA), along with improved clinical symptoms. Among 40 treated patients, the combination demonstrated a favorable safety profile with low immune-related adverse events and only 5% reporting colitis. Of the 18 patients evaluable for response, 11 without liver metastases showed promising results, with responses ongoing at data cutoff.
The company plans to report updated Phase 2 data in mid-2025 and is seeking partnership opportunities to expand development beyond the initial MSS CRC trial.
Xilio Therapeutics (Nasdaq: XLO) ha annunciato i primi dati della Fase 2 per vilastobart (XTX101) combinato con atezolizumab nel trattamento del cancro colorettale metastatico microsatellite stabile (MSS CRC). Lo studio ha mostrato un tasso di risposta preliminare del 27% nei pazienti senza metastasi epatiche, con tre risposte parziali, di cui due confermate.
I risultati chiave includono la diminuzione dei livelli dell'antigene carcinoembrionario (CEA) e del DNA tumorale circolante (ctDNA), insieme a sintomi clinici migliorati. Dei 40 pazienti trattati, la combinazione ha dimostrato un profilo di sicurezza favorevole con eventi avversi immmuno-correlati poco frequenti e solo il 5% dei pazienti che riporta colite. Dei 18 pazienti valutabili per risposta, 11 senza metastasi epatiche hanno mostrato risultati promettenti, con risposte in corso al momento della chiusura dei dati.
L'azienda prevede di riportare dati aggiornati della Fase 2 a metà 2025 e sta cercando opportunità di partnership per espandere lo sviluppo oltre il trial iniziale su MSS CRC.
Xilio Therapeutics (Nasdaq: XLO) anunció los datos iniciales de la Fase 2 para vilastobart (XTX101) combinado con atezolizumab en el tratamiento del cáncer colorrectal metastásico estable en microsatélites (MSS CRC). El ensayo mostró un tasa de respuesta preliminar del 27% en pacientes sin metástasis hepáticas, con tres respuestas parciales, incluidas dos confirmadas.
Entre los hallazgos clave se incluyen la disminución de los niveles del antígeno carcinoembrionario (CEA) y del ADN tumoral circulante (ctDNA), junto con la mejora de los síntomas clínicos. De los 40 pacientes tratados, la combinación demostró un perfil de seguridad favorable con eventos adversos relacionados con el sistema inmunológico bajos y solo el 5% reportando colitis. De los 18 pacientes evaluables para respuesta, 11 sin metástasis hepáticas mostraron resultados prometedores, con respuestas en curso en el corte de datos.
La empresa planea informar sobre datos actualizados de la Fase 2 a mediados de 2025 y está buscando oportunidades de asociación para expandir el desarrollo más allá del ensayo inicial de MSS CRC.
Xilio Therapeutics (Nasdaq: XLO)는 전이성 마이크로새틀라이트 안정 대장암(MSS CRC) 치료를 위해 atezolizumab과 결합된 vilastobart (XTX101)의 초기 2단계 데이터를 발표했습니다. 이 시험에서는 간 전이가 없는 환자에서 27%의 예비 반응률을 보였으며, 3명의 부분 반응이 포함되었고 그 중 2명이 확인되었습니다.
주요 발견 사항으로는 카르시노엠브리오닉 항원(CEA) 및 순환 종양 DNA(ctDNA) 수치 감소와 함께 임상 증상이 개선되었음을 포함합니다. 치료받은 40명의 환자 중 이 조합은 면역 관련 부작용이 낮고 단지 5%만이 대장염을 보고하는 등 유리한 안전성 프로필을 보여주었습니다. 반응 평가가 가능한 18명의 환자 중 간 전이가 없는 11명이 유망한 결과를 보였고, 데이터 마감 시점에서도 반응이 계속되고 있었습니다.
회사는 2025년 중반에 2단계 데이터 업데이트를 보고할 계획이며, 초기 MSS CRC 시험을 넘어서 개발을 확장하기 위한 파트너십 기회를 모색하고 있습니다.
Xilio Therapeutics (Nasdaq: XLO) a annoncé des données préliminaires de la Phase 2 pour vilastobart (XTX101) en combinaison avec atezolizumab dans le traitement du cancer colorectal métastatique stable en microsatellites (MSS CRC). L'essai a montré un taux de réponse préliminaire de 27% chez les patients sans métastases hépatiques, avec trois réponses partielles, dont deux confirmées.
Les résultats clés incluent une diminution des niveaux de l'antigène carcinoembryonnaire (CEA) et de l'ADN tumoral circulant (ctDNA), ainsi qu'une amélioration des symptômes cliniques. Parmi les 40 patients traités, la combinaison a montré un profil de sécurité favorable avec peu d'événements indésirables liés à l'immunité et seulement 5 % signalant une colite. Parmi les 18 patients évaluables pour la réponse, 11 sans métastases hépatiques ont montré des résultats prometteurs, avec des réponses en cours à la date limite de données.
L'entreprise prévoit de communiquer des données mises à jour de la Phase 2 à la mi-2025 et cherche des opportunités de partenariat pour élargir le développement au-delà de l'essai initial sur le MSS CRC.
Xilio Therapeutics (Nasdaq: XLO) gab die ersten Daten der Phase 2 zu vilastobart (XTX101) in Kombination mit atezolizumab zur Behandlung von metastasiertem mikrosatellitenstabilem kolorektalem Krebs (MSS CRC) bekannt. Die Studie zeigte eine vorläufige Ansprechrate von 27% bei Patienten ohne Lebermetastasen, darunter drei partielle Anspreche, von denen zwei bestätigt wurden.
Zu den wichtigen Ergebnissen gehören verringerte Werte des carcinoembryonalen Antigens (CEA) und der zirkulierenden tumoralen DNA (ctDNA) sowie verbesserte klinische Symptome. Von 40 behandelten Patienten zeigte die Kombination ein günstiges Sicherheitsprofil mit wenigen immunbedingten Nebenwirkungen und nur 5% berichteten von Colitis. Von den 18 Patienten, die auf Ansprechen bewertet wurden, zeigten 11 ohne Lebermetastasen vielversprechende Ergebnisse, wobei die Ansprechen zum Zeitpunkt des Datenschnitts andauerten.
Das Unternehmen plant, Mitte 2025 aktualisierte Phase-2-Daten zu veröffentlichen und sucht Partnerschaftsmöglichkeiten zur Erweiterung der Entwicklung über die ursprüngliche MSS CRC-Studie hinaus.
- 27% preliminary response rate in MSS CRC patients without liver metastases
- Two confirmed partial responses with tumor size reductions of 47% and 57%
- Low incidence of immune-related adverse events (5% colitis)
- 23 patients still ongoing treatment as of data cutoff
- Disease control rate of 55% in patients without liver metastases
- efficacy in patients with liver metastases (14% disease control rate)
- Three patients discontinued treatment due to adverse events
- Six patients experienced Grade 3 or 4 treatment-related adverse events
Insights
The preliminary Phase 2 data for Xilio Therapeutics' vilastobart (XTX101) represents a potentially significant advancement in treating microsatellite stable colorectal cancer (MSS CRC), a notoriously difficult-to-treat cancer type that typically shows no response to immunotherapy.
Key clinical highlights:
- Efficacy Data: The
27% response rate in non-liver metastasis patients is particularly noteworthy, as standard immunotherapies historically show negligible efficacy in MSS CRC. The observed responses were supported by multiple validation points including CEA normalization, ctDNA reductions and symptom improvements. - Safety Profile: The drug combination demonstrated a favorable safety profile with only
5% of patients experiencing Grade 3 colitis, which is notably lower than historical rates seen with other CTLA-4 inhibitors. - Patient Population: The heavily pre-treated nature of the study population (
70% with 3+ prior therapy lines) makes these results more impressive, as these patients typically have treatment options.
For investors, several aspects warrant attention:
- Market Potential: MSS CRC represents approximately
95% of all colorectal cancer cases, suggesting a substantial market opportunity if the drug advances successfully. - Development Strategy: Xilio's decision to seek partnership opportunities indicates a strategic pivot that could accelerate development while managing costs - a important consideration given the company's market cap of
$53.9M . - Risk Factors: While promising, these are early Phase 2 results with a relatively small patient population. The pending confirmation of some responses and upcoming data updates in mid-2025 will be critical validation points.
The data suggests vilastobart could potentially address a significant unmet medical need in MSS CRC treatment, though investors should monitor the upcoming expanded dataset and partnership developments as key catalysts.
The vilastobart data represents a potential paradigm shift in MSS CRC treatment, where current immunotherapy approaches have consistently failed. Let's break down the clinical significance:
Scientific Breakthrough: The tumor-activated mechanism of vilastobart appears to overcome two major challenges in immunotherapy:
- Selective activation in the tumor microenvironment, potentially explaining the improved safety profile compared to traditional CTLA-4 inhibitors
- Ability to convert "cold" tumors (immunologically unresponsive) into "hot" ones, as evidenced by the responses in MSS CRC patients
Clinical Validation: The multi-modal confirmation of responses is particularly compelling:
- Radiographic responses (up to
57% tumor reduction) - Biomarker improvements (CEA normalization and ctDNA reductions)
- Symptom improvement
The
The safety profile is notably superior to traditional CTLA-4 inhibitors like ipilimumab, which typically show much higher rates of immune-related adverse events. This could potentially enable longer treatment durations and better outcomes.
Responses were accompanied by decreases in levels of carcinoembryonic antigen (CEA) and circulating tumor DNA (ctDNA) and improvement in clinical symptoms
Data continue to demonstrate differentiated safety and tolerability profile for the combination with low incidence of immune-related adverse events
Xilio Therapeutics to host investor conference call and webcast on Wednesday, January 22, 2025, at 8:30 am ET
WALTHAM, Mass., Jan. 21, 2025 (GLOBE NEWSWIRE) -- Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology therapies for people living with cancer, today announced initial data from its ongoing Phase 2 clinical trial evaluating vilastobart (XTX101), a tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4, in combination with atezolizumab (Tecentriq®) in patients with metastatic microsatellite stable colorectal cancer (MSS CRC). The data will be presented in a poster session (abstract #206) at the American Society of Clinical Oncology 2025 Gastrointestinal Cancer Symposium (ASCO GI) being held January 23-25, 2025, in San Francisco.
“We are very encouraged by the initial Phase 2 proof-of-concept data for the combination of vilastobart and atezolizumab in heavily pre-treated patients with MSS colorectal cancer, including partial responses accompanied by marked decreases in tumor biomarkers and improvement in clinical symptoms,” said Katarina Luptakova, M.D., chief medical officer of Xilio. “We believe these data highlight the important contribution of vilastobart in this combination, as PD-(L)1 inhibitors alone have demonstrated no meaningful efficacy in patients with MSS CRC to date. The preliminary evidence of anti-tumor activity, together with continued evidence of a well-tolerated safety profile, support the potential for the combination in MSS colorectal cancer, as well as in other tumors that have traditionally been resistant to treatment with immunotherapy. 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.”
“These preliminary Phase 2 data for the combination of vilastobart and atezolizumab show clear responses for patients with MSS colorectal cancer, an area of very high and increasing unmet medical need,” said J. Randolph Hecht, M.D., Professor of Clinical Medicine at the David Geffen School of Medicine at UCLA, Director of the UCLA Gastrointestinal Oncology Program and the lead author for the presentation at ASCO GI. “I am excited to see these initial data highlighting the potential for vilastobart, a tumor-activated anti-CTLA-4, in combination with PD-(L)1 inhibitors to have clinically meaningful benefit in a classically immunotherapy-resistant major malignancy.”
Data from Phase 2 Trial for Vilastobart (XTX101), a Tumor-Activated Anti-CTLA-4, in Combination with Atezolizumab in Patients with Metastatic MSS CRC
As of a data cutoff date of January 13, 2025, 40 patients with metastatic MSS CRC had been treated with the combination of vilastobart at a dose of 100 mg once every six weeks (Q6W) and atezolizumab at 1200 mg once every three weeks (Q3W). The median age was 55 years (ranging from 25 to 82 years), and patients were heavily pre-treated, with
Preliminary Anti-Tumor Activity Data
In patients without liver metastases, the preliminary objective response rate (ORR) was
As of the data cutoff date, 18 patients had at least one imaging scan reported and were evaluable for response assessment (per RECIST version 1.1 criteria), including 11 patients without liver metastases and seven patients with liver metastases.
In response-evaluable MSS CRC patients without liver metastases, investigators reported three PRs (two confirmed, one pending confirmation), with each patient ongoing on treatment as of the data cutoff date:
- PR (confirmed) with a
47% decrease in the sum of diameters of target lesions at 13 weeks accompanied by a decrease in levels of the serum tumor marker CEA, a multi-log fold decrease in levels of ctDNA and improvement of clinical symptoms, such as cough. CEA is a serum biomarker that is often elevated in many malignancies, including colorectal cancer, and ctDNA is a biomarker found in the bloodstream of patients with cancer. - PR (confirmed) that continued to deepen over time with a
57% reduction in the sum of diameters of target lesions at 18 weeks accompanied by a multi-log fold decrease in ctDNA to undetectable levels and significant decrease in levels of the serum tumor marker CEA to normal values. - PR (pending confirmation) with a
35% decrease in the sum of diameters of target lesions at nine weeks accompanied by a decrease in levels of the tumor marker CEA to normal values, a substantial decrease in levels of ctDNA and improvement of clinical symptoms, such as cough. For this patient, the initial response on CT imaging was assessed by the investigator and the radiology assessment is pending.
In addition, an MSS CRC patient without liver metastases but with a peritoneal metastasis had a
Investigators reported stable disease in three patients without liver metastases and one patient with liver metastases, representing a preliminary disease control rate of
As of the data cutoff date, 23 patients were ongoing on treatment, including 13 patients who had not yet had a first response assessment.
Preliminary Safety Data
Safety data continue to support the potential for vilastobart to be a differentiated next-generation anti-CTLA-4 in combination with PD-(L)1 inhibitors. Consistent with the tumor-selective design for vilastobart, the combination was generally well-tolerated, with patients experiencing a low incidence of immune-related adverse events (irAEs) and only
As of the data cutoff date, 40 patients were evaluable for safety. Across all patients treated:
- Investigators reported only six patients with Grade 3 or 4 treatment-related adverse events (AEs), including only two Grade 4 treatment-related AEs (laboratory abnormalities of thrombocytopenia and neutropenia, one patient each), and no Grade 5 treatment-related AEs.
- No patients experienced a dose reduction for vilastobart due to an AE, and only three patients discontinued treatment for the combination of vilastobart and atezolizumab due to a treatment-related AE.
- Investigators reported minimal endocrine irAEs (
5% ) and limited skin irAEs (13% ), and the incidence of endocrine and skin irAEs was consistent with the incidence reported for atezolizumab alone. - The most common treatment-related AEs (≥
10% incidence) of any grade reported by investigators were the following: fatigue (30% ); diarrhea (20% ); infusion-related reactions (13% , with8% deemed related to vilastobart and5% deemed related to atezolizumab); pyrexia (10% ); aspartate aminotransferase (AST) increase (10% ); and alanine aminotransferase (ALT) increase (10% ). - The only Grade 3 treatment-related AE with ≥
5% incidence reported by investigators was colitis (5% ). Non-laboratory Grade 3 treatment-related AEs (<5% incidence) consisted of the following: maculopapular rash and febrile neutropenia in one patient; lower gastrointestinal hemorrhage in one patient with thrombocytopenia; and one patient with Triple M overlap syndrome (myocarditis, myositis and myasthenia gravis).
Clinical Development Plans for Vilastobart
The Phase 2 clinical trial evaluating vilastobart in combination with atezolizumab in patients with MSS CRC is currently ongoing, and Xilio expects to report updated data from the Phase 2 trial in the middle of 2025, including additional response assessments and follow-up.
These initial Phase 2 proof-of-concept data demonstrate the potential for vilastobart as a combination therapy in patients with MSS CRC and a range of other tumor types, including “cold” tumors historically resistant to immunotherapy. Based on these data, Xilio plans to seek opportunities for partnering to prioritize and expand further development beyond the initial Phase 2 proof-of-concept trial in MSS CRC.
In addition, Xilio continues to enroll patients in Phase 1C dose escalation and evaluate the combination of vilastobart at the 150 mg Q6W dose level and atezolizumab at 1200 mg Q3W.
Investor Conference Call Information
Xilio will host a conference call and webcast tomorrow (Wednesday, January 22, 2025) at 8:30 am ET to discuss the initial Phase 2 data for the combination of vilastobart and atezolizumab. Viewers can access the webcast by using this link. Listeners who require dial-in access should register here to receive a unique PIN and information to join the call. Listeners are encouraged to join at least 15 minutes prior to the scheduled start time. The webcast will also be accessible under “Events & Presentations” in the Investors & Media section of the Xilio Therapeutics website at https://ir.xiliotx.com. A replay of the webcast will be archived on the website for 30 days following the presentation.
About Vilastobart (XTX101) and the Phase 1/2 Combination Clinical Trial
Vilastobart is an investigational tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4 monoclonal antibody designed to block CTLA-4 and deplete regulatory T cells when activated in the tumor microenvironment (TME). In 2023, Xilio entered into a co-funded clinical trial collaboration with Roche to evaluate vilastobart in combination with atezolizumab (Tecentriq®) in a multi-center, open-label Phase 1/2 clinical trial. Xilio is currently evaluating the safety of the combination in Phase 1C dose escalation in patients with advanced solid tumors and the safety and efficacy of the combination in Phase 2 in patients with metastatic microsatellite stable colorectal cancer with and without liver metastases. Please refer to NCT04896697 on www.clinicaltrials.gov for additional details.
About Xilio Therapeutics
Xilio Therapeutics is a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology (I-O) therapies with the goal of significantly improving outcomes for people living with cancer without the systemic side effects of current I-O treatments. The company is using its proprietary platform to advance a pipeline of novel, tumor-activated clinical and preclinical I-O molecules that are designed to optimize the therapeutic index by localizing anti-tumor activity within the tumor microenvironment, including tumor-activated cytokines, antibodies, bispecifics and immune cell engagers. Learn more by visiting www.xiliotx.com and follow us on LinkedIn (Xilio Therapeutics, Inc.).
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding plans, expectations and anticipated milestones for vilastobart (XTX101), including plans and timing for reporting Phase 2 clinical data for vilastobart in combination with atezolizumab in patients with MSS CRC; the potential benefits of vilastobart (as a monotherapy or combination therapy with a PD-(L)1 or other agent) or any of Xilio’s other current or future product candidates in treating patients as a monotherapy or combination therapy in any indication; the ultimate safety profile of vilastobart; and Xilio’s strategy, goals and anticipated financial performance, milestones, business plans and focus. The words “aim,” “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “seek,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of important risks, uncertainties and other factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, general market conditions; risks and uncertainties related to ongoing and planned research and development activities, including initiating, conducting or completing preclinical studies and clinical trials and the timing and results of such preclinical studies or clinical trials; the delay of any current or planned preclinical studies or clinical trials or the development of Xilio’s current or future product candidates; Xilio’s ability to obtain and maintain sufficient preclinical and clinical supply of current or future product candidates; Xilio’s advancement of multiple early-stage immune cell engager programs, including tumor-activated immune cell engagers and tumor-activated effector-enhanced immune cell engagers; initial, preliminary or interim preclinical or clinical data or results (including without limitation, the Phase 2 data for vilastobart and the preliminary investigator-reported PR awaiting radiology confirmation), which may not be replicated in or predictive of future preclinical or clinical data or results; Xilio’s ability to successfully demonstrate the safety and efficacy of its product candidates and gain approval of its product candidates on a timely basis, if at all; results from preclinical studies or clinical trials for Xilio’s product candidates, which may not support further development of such product candidates; actions of regulatory agencies, which may affect the initiation, timing and progress of current or future clinical trials; Xilio’s ability to obtain, maintain and enforce patent and other intellectual property protection for current or future product candidates; Xilio’s ability to obtain and maintain sufficient cash resources to fund its operations; the impact of international trade policies on Xilio’s business, including U.S. and China trade policies; Xilio’s ability to maintain its clinical trial collaboration with Roche to develop vilastobart in combination with atezolizumab; and Xilio’s ability to maintain its license agreement with Gilead to develop and commercialize XTX301. These and other risks and uncertainties are described in greater detail in the sections entitled “Risk Factor Summary” and “Risk Factors” in Xilio’s filings with the U.S. Securities and Exchange Commission (SEC), including Xilio’s most recent Quarterly Report on Form 10-Q and any other filings that Xilio has made or may make with the SEC in the future. Any forward-looking statements contained in this press release represent Xilio’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Xilio explicitly disclaims any obligation to update any forward-looking statements.
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Investor and Media Contact
Scott Young
Vice President, Investor Relations and Corporate Communications
investors@xiliotx.com
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