XTX101 Monotherapy and XTX101 and Atezolizumab Combination Therapy in Patients With Advanced Solid Tumors

Advanced Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04896697
• Other study ID #: XTX101-01/02-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 13, 2021
• Est. completion date: March 30, 2026

Study information

• Verified date: August 2023
• Source: Xilio Development, Inc.
• Contact: Teleen Norman
• Phone: 203-584-5310
• Email: tnorman[@]xiliotx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Part 1A will examine 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 XTX101 monotherapy in relation to specific PD biomarkers.

Part 1C will examine XTX101 in combination with atezolizumab in a standard 3+3 dose escalation/dose de-escalation design.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 96
• Est. completion date: March 30, 2026
• Est. primary completion date: March 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

• ECOG performance status of 0 or 1

• Adequate organ function

• Part 1B and Part 1C 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 systemic anticancer therapy within 4 weeks prior to study treatment

• Received prior radiotherapy within 2 weeks prior to study treatment

• 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

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• XTX101
XTX101 monotherapy
• Atezolizumab
1200 mg administered every 3 weeks in combination with XTX101
• XTX101
In combination with Atezolizumab

Locations

Country	Name	City	State
United States	Next Oncology	Austin	Texas
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	California Cancer Associates for Research and Excellence, cCARE	Encinitas	California
United States	NEXT Virginia	Fairfax	Virginia
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	Sarah Cannon Research Institute at Florida Cancer Specialists	Orlando	Florida
United States	University of Pittsburgh Medical Center- Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	California Cancer Associates for Research and Excellence, cCARE	San Marcos	California
United States	Tranquil Clinical Research	Webster	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Xilio Development, Inc.	Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	Incidence of Dose Limiting Toxicities (DLTs) in Part 1C		Cycle 1 Day 1 up to Cycle 3 Day 1 (approximately 6 weeks)
Primary	Incidence of treatment-emergent adverse events		Up to 24 months
Primary	Incidence of changes in clinical laboratory abnormalities		Up to 24 months
Secondary	Investigator-assessed objective response rate (ORR) per iRECIST		Up to 24 months
Secondary	Antidrug antibody (ADA) occurrence and titer in serum		Up to 24 months
Secondary	Plasma concentrations of XTX101 (total and intact)		Up to Cycle 8 (21 days per cycle)
Secondary	Maximum observed plasma concentration (Cmax)		Up to Cycle 8 (21 days per cycle)
Secondary	Time of maximum observed concentration (Tmax)		Up to Cycle 8 (21 days per cycle)
Secondary	Trough concentrations (Ctrough)		Up to Cycle 8 (21 days per cycle)
Secondary	Area under the curve (AUC)		Up to Cycle 8 (21 days per cycle)
Secondary	Half-life (T1/2)		Up to Cycle 8 (21 days per cycle)
Secondary	Systemic clearance (CL)		Up to Cycle 8 (21 days per cycle)
Secondary	Volume of distribution (Vd)		Up to Cycle 8 (21 days per cycle)