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

NCT04896697 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: XTX101-01/02-001
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 19

Brief Summary

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.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (17)

• 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

Study Arms (4)

Part 1A - vilastobart (XTX101) Monotherapy Dose Escalation

EXPERIMENTAL

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)

Part 1B - Pharmacodynamic (PD) Dose Expansion

EXPERIMENTAL

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)

Part 1C - vilastobart (XTX101) Dose Escalation and Dose Expansion in Combination with Atezolizumab

EXPERIMENTAL

Part 1C will receive a labeled dose of atezolizumab in combination with vilastobart (XTX101).

Drug: Atezolizumab; Drug: vilastobart (XTX101)

Phase 2 - vilastobart (XTX101) Dose Expansion in Combination with Atezolizumab

EXPERIMENTAL

Phase 2 will receive a labeled dose of atezolizumab in combination with vilastobart (XTX101) at the RP2D(s) in patients with MSS CRC.

Drug: Atezolizumab; Drug: vilastobart (XTX101)

Interventions

vilastobart (XTX101) DRUG

vilastobart (XTX101) monotherapy

Part 1A - vilastobart (XTX101) Monotherapy Dose Escalation; Part 1B - Pharmacodynamic (PD) Dose Expansion

Atezolizumab DRUG

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

Part 1C - vilastobart (XTX101) Dose Escalation and Dose Expansion in Combination with Atezolizumab; Phase 2 - vilastobart (XTX101) Dose Expansion in Combination with Atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Xilio Development, Inc.: lead
• Hoffmann-La Roche: collaborator

Study Sites (19)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

California Cancer Associates for Research and Excellence, cCARE

Encinitas, California, 92024, United States

Location

City of Hope-Lennar

Irvine, California, 92618, United States

Location

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

California Cancer Associates for Research and Excellence, cCARE

San Marcos, California, 92069, United States

Location

UCLA Hematology/Oncology- Santa Monica

Santa Monica, California, 90404, United States

Location

City of Hope-Upland

Upland, California, 91786, United States

Location

Mayo Clinic Hospital

Jacksonville, Florida, 32224, United States

Location

Sarah Cannon Research Institute at Florida Cancer Specialists

Orlando, Florida, 32827, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic Hospital

Rochester, Minnesota, 55905, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Carolina BioOncology Institute

Huntersville, North Carolina, 28078, United States

Location

University of Pittsburgh Medical Center- Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Next Oncology

Austin, Texas, 78758, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

Location

Tranquil Clinical Research

Webster, Texas, 77598, United States

Location

NEXT Virginia

Fairfax, Virginia, 22031, United States

Location

Related Publications (1)

• 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.

  PMID: 38164757 DERIVED

MeSH Terms

Interventions

atezolizumab

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2021
• First Posted: May 21, 2021
• Study Start: September 13, 2021
• Primary Completion (Estimated): June 12, 2026
• Study Completion (Estimated): June 12, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (19)