Vilastobart (XTX101) Monotherapy and Vilastobart and Atezolizumab Combination Therapy in Advanced Solid Tumors
- Conditions
- Advanced Solid Tumor
- Interventions
- Drug: vilastobart (XTX101)
- Registration Number
- NCT04896697
- Lead Sponsor
- Xilio Development, Inc.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 136
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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1A - vilastobart (XTX101) Monotherapy Dose Escalation vilastobart (XTX101) 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). Part 1B - Pharmacodynamic (PD) Dose Expansion vilastobart (XTX101) Part 1B vilastobart (XTX101) at the RP2D will be administered to further examine vilastobart (XTX101) as monotherapy in patients with select advanced solid tumors. Part 1C - vilastobart (XTX101) Dose Escalation and Dose Expansion in Combination with Atezolizumab Atezolizumab Part 1C will receive a labeled dose of atezolizumab in combination with vilastobart (XTX101). Part 1C - vilastobart (XTX101) Dose Escalation and Dose Expansion in Combination with Atezolizumab vilastobart (XTX101) Part 1C will receive a labeled dose of atezolizumab in combination with vilastobart (XTX101). Phase 2 - vilastobart (XTX101) Dose Expansion in Combination with Atezolizumab Atezolizumab Phase 2 will receive a labeled dose of atezolizumab in combination with vilastobart (XTX101) at the RP2D(s) in patients with MSS CRC. Phase 2 - vilastobart (XTX101) Dose Expansion in Combination with Atezolizumab vilastobart (XTX101) Phase 2 will receive a labeled dose of atezolizumab in combination with vilastobart (XTX101) at the RP2D(s) in patients with MSS CRC.
- Primary Outcome Measures
Name Time Method 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 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 treatment-emergent adverse events in Part 1 Up to 24 months Incidence of Dose Limiting Toxicities (DLTs) in Part 1C Cycle 1 Day 1 up to Cycle 3 Day 1 (approximately 6 weeks)
- Secondary Outcome Measures
Name Time Method Disease control rate in Phase 2 Up to 24 months The percent of patients who achieve complete response per iRECIST (iCR), partial response per iRECIST (iPR), or stable disease per iRECIST (iSD)
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 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 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 Up to 24 months The time from first documented confirmed response to first documented disease progression
Plasma concentrations of vilastobart (XTX101) (total and intact) 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 Progression-free survival per iRECIST in Phase 2 Up to 24 months The time from first dose to first documented disease progression or death
Overall survival in Phase 2 Up to 24 months The time from first dose to death due to any cause
Trial Locations
- Locations (16)
Mayo Clinic Hospital
🇺🇸Rochester, Minnesota, United States
City of Hope
🇺🇸Duarte, California, United States
California Cancer Associates for Research and Excellence, cCARE
🇺🇸San Marcos, California, United States
City of Hope-Lennar
🇺🇸Irvine, California, United States
USC/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
UCLA Hematology/Oncology- Santa Monica
🇺🇸Santa Monica, California, United States
City of Hope-Upland
🇺🇸Upland, California, United States
Sarah Cannon Research Institute at Florida Cancer Specialists
🇺🇸Orlando, Florida, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Scroll for more (6 remaining)Mayo Clinic Hospital🇺🇸Rochester, Minnesota, United StatesClinical Trials Referral OfficeContact855-776-0015