Vilastobart (XTX101) Monotherapy and Vilastobart and Atezolizumab Combination Therapy in Advanced Solid Tumors

A First-in-Human, Multicenter, Phase 1/2, Open-Label Study of Vilastobart (XTX101) Monotherapy and Vilastobart (XTX101) and Atezolizumab Combination Therapy in Patients With Advanced Solid Tumors

This is a first-in-human, Phase 1/2, multicenter, open-label study designed to evaluate the safety and tolerability of vilastobart (XTX101) as monotherapy and vilastobart (XTX101) and atezolizumab combination therapy in patients with advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: vilastobart (XTX101); Drug: vilastobart (XTX101); Drug: Atezolizumab

Detailed Description

This is a first-in-human, Phase 1/2, multicenter, open-label study designed to evaluate the safety and tolerability of vilastobart (XTX101), a tumor-selective anti-CTLA-4 antibody, as monotherapy and vilastobart (XTX101) and atezolizumab combination therapy in patients with advanced solid tumors.

Part 1A will examine vilastobart (XTX101) monotherapy in an accelerated and standard 3+3 dose escalation design. Based on the results of Part 1A, patients with select advanced solid tumors will be enrolled in Part 1B, which will evaluate vilastobart (XTX101) monotherapy in relation to specific PD biomarkers.

Part 1C will examine vilastobart (XTX101) in combination with atezolizumab in a standard 3+3 dose escalation/dose de-escalation design. Part 1C may include a dose expansion cohort to further evaluate the safety, PK, and PD of dose levels that were previously cleared.

Phase 2 will examine vilastobart (XTX101) in combination with atezolizumab in patients with metastatic microsatellite stable colorectal cancer (MSS CRC) at the RP2D(s) defined in Part 1C.

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Hospital
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Encinitas, California, United States, 92024
      • California Cancer Associates for Research and Excellence, cCARE
    • Irvine, California, United States, 92618
      • City of Hope-Lennar
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center
    • San Marcos, California, United States, 92069
      • California Cancer Associates for Research and Excellence, cCARE
    • Santa Monica, California, United States, 90404
      • UCLA Hematology/Oncology- Santa Monica
    • Upland, California, United States, 91786
      • City of Hope-Upland
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Hospital
    • Orlando, Florida, United States, 32827
      • Sarah Cannon Research Institute at Florida Cancer Specialists
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Huntersville, North Carolina, United States, 28078
      • Carolina BioOncology Institute
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center- Hillman Cancer Center
  • Texas
    • Austin, Texas, United States, 78758
      • NEXT Oncology
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research
    • Webster, Texas, United States, 77598
      • Tranquil Clinical Research
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • NEXT Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Disease Criteria -

• Part 1A and 1C: Any histologically or cytologically confirmed solid tumor malignancy that is locally advanced or metastatic and has failed standard therapy, or standard therapy is not curative or available;

• Part 1B:

  • Any histologically or cytologically confirmed solid tumor malignancy for which anti-PD-1 or anti-PD-L1 treatment is approved and has progressed on or after prior anti-PD-1 or anti-PD-L1 therapy.
  • Patients with metastatic castrate-resistant prostate cancer if they have progressed on at least 2 lines of systemic therapy
  • Patients with extensive stage small cell lung cancer (SCLC) after at least 1 line of prior therapy
  • Patients with microsatellite stable colorectal cancer after at least 2 lines of prior therapy

• Phase 2: Patients with histologically confirmed metastatic MSS CRC are eligible to enroll in Phase 2 as follows:

  • Patients must have had at least 1 prior chemotherapy regimen for metastatic CRC including all of the following agents: a fluoropyrimidine, irinotecan, oxaliplatin, bevacizumab or biosimilars, an anti epidermal growth factor receptor antibody (cetuximab or panitumumab), and v-raf murine sarcoma viral oncogene homolog B1 inhibitor/BRAF (encorafenib), if applicable
  • Patients with MSI-H/dMMR are excluded
• ECOG performance status of 0 or 1
• Adequate organ function
• Part 1B, Part 1C, and Phase 2 only: measurable disease per iRECIST

Exclusion Criteria:

• Received prior treatment with anti-CTLA-4 therapy
• Received prior immune-checkpoint therapy and experienced Grade 3 or greater toxicity lasting greater than 6 weeks
• Received prior approved systemic anticancer therapy within 4 weeks prior to study treatment
• Received prior radiotherapy within 2 weeks prior to study treatment
• Phase 2 only: Received prior anti-PD-1/L1 therapy or any investigational checkpoint inhibitory therapy
• Has a diagnosis of immunodeficiency
• Has known malignancy (other than disease under study) that is progressing or has required active treatment within the past 3 years
• Has an active autoimmune disease that has required systemic treatment in past 2 years, including the use of disease modifying agents, corticosteroids or immunosuppressive drugs
• Has an active infection requiring systemic intravenous therapy within 4 weeks prior to study treatment, or oral therapy within 2 weeks prior to study treatment
• Has a history of severe hypersensitivity reaction (≥ Grade 3) to any study intervention and/or any of its excipients
• Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
• Phase 2 only: symptomatic bowel obstruction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1A - vilastobart (XTX101) Monotherapy Dose Escalation; Part 1A Dose Escalation of vilastobart (XTX101) administered in ascending doses to patients with advanced or metastatic solid tumors to find the recommended phase 2 dose (RP2D).	Drug: vilastobart (XTX101); vilastobart (XTX101) monotherapy; Drug: vilastobart (XTX101); In combination with Atezolizumab
Experimental: Part 1B - Pharmacodynamic (PD) Dose Expansion; Part 1B vilastobart (XTX101) at the RP2D will be administered to further examine vilastobart (XTX101) as monotherapy in patients with select advanced solid tumors.	Drug: vilastobart (XTX101); vilastobart (XTX101) monotherapy; Drug: vilastobart (XTX101); In combination with Atezolizumab
Experimental: Phase 2 - vilastobart (XTX101) Dose Expansion in Combination with Atezolizumab; Phase 2 will receive a labeled dose of atezolizumab in combination with vilastobart (XTX101) at the RP2D(s) in patients with MSS CRC.	Drug: vilastobart (XTX101); vilastobart (XTX101) monotherapy; Drug: vilastobart (XTX101); In combination with Atezolizumab; Drug: Atezolizumab; 1200 mg administered every 3 weeks in combination with vilastobart (XTX101)
Experimental: Part 1C - vilastobart (XTX101) Dose Escalation and Dose Expansion in Combination with Atezolizumab; Part 1C will receive a labeled dose of atezolizumab in combination with vilastobart (XTX101).	Drug: vilastobart (XTX101); vilastobart (XTX101) monotherapy; Drug: vilastobart (XTX101); In combination with Atezolizumab; Drug: Atezolizumab; 1200 mg administered every 3 weeks in combination with vilastobart (XTX101)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Dose Limiting Toxicities (DLTs) in Part 1A	Cycle 1 Day 1 up to just prior to the second dose of study drug at Cycle 2 day 1 (approximately 3 weeks)
Incidence of Dose Limiting Toxicities (DLTs) in Part 1C	Cycle 1 Day 1 up to Cycle 3 Day 1 (approximately 6 weeks)
Incidence of treatment-emergent adverse events in Part 1	Up to 24 months
Incidence of changes in clinical laboratory abnormalities in Part 1	Up to 24 months
Investigator-assessed objective response rate (ORR) per iRECIST in Phase 2	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-assessed objective response rate (ORR) per iRECIST in Part 1		Up to 24 months
Antidrug antibody (ADA) occurrence and titer in serum in Part 1		Up to 24 months
Plasma concentrations of vilastobart (XTX101) (total and intact) in Part 1 and Phase 2		Up to 24 months
Maximum observed plasma concentration (Cmax) in Part 1 and Phase 2		Up to 24 months
Time of maximum observed concentration (Tmax) in Part 1 and Phase 2		Up to 24 months
Trough concentrations (Ctrough) in Part 1 and Phase 2		Up to 24 months
Area under the curve (AUC) in Part 1 and Phase 2		Up to 24 months
Half-life (T1/2) in Part 1 and Phase 2		Up to 24 months
Systemic clearance (CL) in Part 1 and Phase 2		Up to 24 months
Volume of distribution (Vd) in Part 1 and Phase 2		Up to 24 months
Investigator-assessed ORR per RECIST in Phase 2		Up to 24 months
Disease control rate in Phase 2	The percent of patients who achieve complete response per iRECIST (iCR), partial response per iRECIST (iPR), or stable disease per iRECIST (iSD)	Up to 24 months
Overall survival in Phase 2	The time from first dose to death due to any cause	Up to 24 months
Incidence of treatment-emergent AEs in Phase 2		Up to 24 months
Incidence of changes in clinical laboratory abnormalities in Phase 2		Up to 24 months
Duration of response per iRECIST in Phase 2	The time from first documented confirmed response to first documented disease progression	Up to 24 months
Progression-free survival per iRECIST in Phase 2	The time from first dose to first documented disease progression or death	Up to 24 months

Collaborators and Investigators

• Sponsor: Xilio Development, Inc.
• Collaborators: Hoffmann-La Roche

Publications and helpful links

General Publications

• Jenkins KA, Park M, Pederzoli-Ribeil M, Eskiocak U, Johnson P, Guzman W, McLaughlin M, Moore-Lai D, O'Toole C, Liu Z, Nicholson B, Flesch V, Qiu H, Clackson T, O'Hagan RC, Rodeck U, Karow M, O'Neil J, Williams JC. XTX101, a tumor-activated, Fc-enhanced anti-CTLA-4 monoclonal antibody, demonstrates tumor-growth inhibition and tumor-selective pharmacodynamics in mouse models of cancer. J Immunother Cancer. 2023 Dec 12;11(12):e007785. doi: 10.1136/jitc-2023-007785.

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2021
• Primary Completion (Actual): May 18, 2026
• Study Completion (Actual): May 18, 2026

Study Registration Dates

• First Submitted: May 6, 2021
• First Submitted That Met QC Criteria: May 17, 2021
• First Posted (Actual): May 21, 2021

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 15, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; atezolizumab
• Other Study ID Numbers: XTX101-01/02-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No