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

NCT ID: NCT04896697

Last Updated: 2025-05-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

136 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-13

Study Completion Date

2026-03-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Advanced Solid Tumor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type EXPERIMENTAL

vilastobart (XTX101)

Intervention Type DRUG

vilastobart (XTX101) monotherapy

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.

Group Type EXPERIMENTAL

vilastobart (XTX101)

Intervention Type DRUG

vilastobart (XTX101) monotherapy

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).

Group Type EXPERIMENTAL

Atezolizumab

Intervention Type DRUG

1200 mg administered every 3 weeks in combination with vilastobart (XTX101)

vilastobart (XTX101)

Intervention Type DRUG

In combination with Atezolizumab

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.

Group Type EXPERIMENTAL

Atezolizumab

Intervention Type DRUG

1200 mg administered every 3 weeks in combination with vilastobart (XTX101)

vilastobart (XTX101)

Intervention Type DRUG

In combination with Atezolizumab

Interventions

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vilastobart (XTX101)

vilastobart (XTX101) monotherapy

Intervention Type DRUG

Atezolizumab

1200 mg administered every 3 weeks in combination with vilastobart (XTX101)

Intervention Type DRUG

vilastobart (XTX101)

In combination with Atezolizumab

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role collaborator

Xilio Development, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Mayo Clinic Hospital

Phoenix, Arizona, United States

Site Status RECRUITING

City of Hope

Duarte, California, United States

Site Status RECRUITING

California Cancer Associates for Research and Excellence, cCARE

Encinitas, California, United States

Site Status RECRUITING

City of Hope-Lennar

Irvine, California, United States

Site Status RECRUITING

USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status RECRUITING

California Cancer Associates for Research and Excellence, cCARE

San Marcos, California, United States

Site Status RECRUITING

UCLA Hematology/Oncology- Santa Monica

Santa Monica, California, United States

Site Status RECRUITING

City of Hope-Upland

Upland, California, United States

Site Status RECRUITING

Mayo Clinic Hospital

Jacksonville, Florida, United States

Site Status RECRUITING

Sarah Cannon Research Institute at Florida Cancer Specialists

Orlando, Florida, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Mayo Clinic Hospital

Rochester, Minnesota, United States

Site Status RECRUITING

Duke University Medical Center

Durham, North Carolina, United States

Site Status RECRUITING

Carolina BioOncology Institute

Huntersville, North Carolina, United States

Site Status COMPLETED

University of Pittsburgh Medical Center- Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Next Oncology

Austin, Texas, United States

Site Status RECRUITING

Mary Crowley Cancer Research

Dallas, Texas, United States

Site Status COMPLETED

Tranquil Clinical Research

Webster, Texas, United States

Site Status RECRUITING

NEXT Virginia

Fairfax, Virginia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Xilio Medical Affairs

Role: CONTACT

857-524-2466

Facility Contacts

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Clinical Trials Referral Office

Role: primary

855-776-0015

Marwan Fakih, MD

Role: primary

Alberto Bessudo, MD

Role: primary

760-452-3340

Marwan Fakih, MD

Role: primary

Charlean Ketchens, RN

Role: primary

Alberto Bessudo, MD

Role: primary

760-452-3340

Rachel Andes

Role: primary

Marwan Fakih, MD

Role: primary

Clinical Trials Referral Office

Role: primary

855-776-0015

Cesar Perez, M.D.

Role: primary

689-216-8500

Aparna Parikh, MD

Role: primary

617-724-4000

Clinical Trials Referral Office

Role: primary

855-776-0015

Nicholas Devito, MD

Role: primary

Julie Urban

Role: primary

412-623-7396

Heather Watson

Role: primary

737-610-5202

Veronica Mohammed

Role: primary

Maybelle De La Rosa

Role: primary

703-783-4518

References

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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.

Reference Type DERIVED
PMID: 38164757 (View on PubMed)

Other Identifiers

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XTX101-01/02-001

Identifier Type: -

Identifier Source: org_study_id

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