Clinical trial NCT04896697: Vilastobart (XTX101) Monotherapy and Vilastobart and Atezolizumab Combination Therapy in Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Lead sponsor: Xilio Development, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Hoffmann-La Roche
First posted: 2021-05-21
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities (DLTs) in Part 1A
timeFrame: Cycle 1 Day 1 up to just prior to the second dose of study drug at Cycle 2 day 1 (approximately 3 weeks)
measure: Incidence of Dose Limiting Toxicities (DLTs) in Part 1C
timeFrame: Cycle 1 Day 1 up to Cycle 3 Day 1 (approximately 6 weeks)
measure: Incidence of treatment-emergent adverse events in Part 1
timeFrame: Up to 24 months
measure: Incidence of changes in clinical laboratory abnormalities in Part 1
timeFrame: Up to 24 months
measure: Investigator-assessed objective response rate (ORR) per iRECIST in Phase 2
timeFrame: Up to 24 months
Secondary outcomes:
measure: Investigator-assessed objective response rate (ORR) per iRECIST in Part 1
timeFrame: Up to 24 months
measure: Antidrug antibody (ADA) occurrence and titer in serum in Part 1
timeFrame: Up to 24 months
measure: Plasma concentrations of vilastobart (XTX101) (total and intact) in Part 1 and Phase 2
timeFrame: Up to 24 months
measure: Maximum observed plasma concentration (Cmax) in Part 1 and Phase 2
timeFrame: Up to 24 months
measure: Time of maximum observed concentration (Tmax) in Part 1 and Phase 2
timeFrame: Up to 24 months
measure: Trough concentrations (Ctrough) in Part 1 and Phase 2
timeFrame: Up to 24 months
measure: Area under the curve (AUC) in Part 1 and Phase 2
timeFrame: Up to 24 months
measure: Half-life (T1/2) in Part 1 and Phase 2
timeFrame: Up to 24 months
measure: Systemic clearance (CL) in Part 1 and Phase 2
timeFrame: Up to 24 months
measure: Volume of distribution (Vd) in Part 1 and Phase 2
timeFrame: Up to 24 months
measure: Investigator-assessed ORR per RECIST in Phase 2
timeFrame: Up to 24 months
measure: Duration of response per iRECIST in Phase 2
timeFrame: Up to 24 months
measure: Disease control rate in Phase 2
timeFrame: Up to 24 months
measure: Progression-free survival per iRECIST in Phase 2
timeFrame: Up to 24 months
measure: Overall survival in Phase 2
timeFrame: Up to 24 months
measure: Incidence of treatment-emergent AEs in Phase 2
timeFrame: Up to 24 months
measure: Incidence of changes in clinical laboratory abnormalities in Phase 2
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Encinitas
country: United States
facility: California Cancer Associates for Research and Excellence, cCARE
state: California
city: Irvine
country: United States
facility: City of Hope-Lennar
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: San Marcos
country: United States
facility: California Cancer Associates for Research and Excellence, cCARE
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology- Santa Monica
state: California
city: Upland
country: United States
facility: City of Hope-Upland
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Hospital
state: Florida
city: Orlando
country: United States
facility: Sarah Cannon Research Institute at Florida Cancer Specialists
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Hospital
state: Minnesota
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center- Hillman Cancer Center
state: Pennsylvania
city: Austin
country: United States
facility: Next Oncology
state: Texas
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Webster
country: United States
facility: Tranquil Clinical Research
state: Texas
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
Study officials:
References: