XTX202 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 XTX202 in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05052268
• Other study ID #: XTX202-01/02-001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: January 18, 2022
• Est. completion date: February 8, 2026

Study information

• Verified date: November 2023
• Source: Xilio Development, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A First-in-Human, Multicenter, Phase 1/2, Open-Label Study of XTX202 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, tolerability, and efficacy of XTX202, an engineered IL-2 prodrug with its activity masked, as monotherapy in patients with advanced solid tumors. Phase 1 Part 1a will examine XTX202 monotherapy in an accelerated and standard 3+3 dose-escalation design. Based on the results of Part 1a, Part 1b will be initiated to further examine XTX202 in patients with select advanced solid tumors and to further characterize XTX202. Based on results of Phase 1 patients with select advanced solid tumors will be enrolled in Phase 2.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 189
• Est. completion date: February 8, 2026
• Est. primary completion date: February 8, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Disease Criteria

• Phase 1, Part 1a: 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
• Phase 1, Part 1b: Histologically or cytologically confirmed solid tumor malignancy with one of the following tumor histologies: RCC of clear cell histology only, melanoma, squamous cell skin carcinoma, ovarian cancer, non-small cell lung cancer. Those patients who previously received immunotherapy must have derived benefit from this treatment. Additionally, patients with any of the above histologies in an advanced setting who plan to undergo debulking surgery or oligometastasectomy may be eligible to receive 2 cycles of XTX202 treatment in a "window of opportunity" subcohort".
• Phase 2, Part 2a: Patients with metastatic RCC who have previously been treated with an anti-PD-1 and a TKI, per local and institutional SOC. Patients must have progressed on treatment with an anti-PD-1 mAb administered either as monotherapy or in combination with other therapies
• Phase 2, Part 2b: Patients with unresectable or metastatic melanoma who have previously been treated with at least 1 prior line of therapy in the recurrent or metastatic setting. Prior therapy must have included an anti-PD-1 alone or in combination per local and institutional standard of care, and patient must have progressed on checkpoint inhibitor therapy. Patients with BRAF V600-activating mutation must have previously received targeted therapy per local and institutional standard of care.

2. ECOG performance status of 0 or 1

3. Adequate organ function

4. Part 1b only patients must be willing to provide fresh tumor biopsies before and after initiation of study treatment.

Exclusion Criteria:

1. Received prior treatment with IL-2 therapy

2. History of clinically significant pulmonary disease

3. History of clinically significant cardiovascular disease

4. Has a diagnosis of immunodeficiency

5. 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

6. Has an active infection requiring systemic therapy within 4 weeks prior to study treatment

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• XTX202
XTX202 Monotherapy

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The Ohio State University Wexner Medical Center James Cancer Hospital and Solove Research Institute	Columbus	Ohio
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of California Los Angeles	Los Angeles	California
United States	Atlantic Health System/Morristown Medical Center	Morristown	New Jersey
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Rutgers Cancer Institute of NJ	New Brunswick	New Jersey
United States	Hoag Memorial Hospital Presbyterian- Newport Beach	Newport Beach	California
United States	UPMC Hillman Cancer Center Pavilion	Pittsburgh	Pennsylvania
United States	HealthPartners Cancer Center at Regions Hospital	Saint Paul	Minnesota
United States	Moffitt Cancer Center	Tampa	Florida
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Xilio Development, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Dose Limiting Toxicities (DLTs) (Phase 1 Part 1A only)		Cycle 1 day 1 up to just prior to the second dose of study drug at Cycle 2 day 1 (each cycle is 21 days)
Primary	Incidence of treatment-emergent adverse events (Phase 1 only)		Up to 24 months
Primary	Incidence of changes in clinical laboratory values (Phase 1 only)		Up to 24 months
Primary	Investigator-assessed objective response rate (ORR) per RECIST 1.1 (Phase 2 only)		Up to 24 months
Secondary	Plasma concentrations of XTX202 (total and intact)		Up to Cycle 7 (21 days per cycle)
Secondary	Maximum observed plasma concentration (Cmax)		Up to Cycle 7 (21 days per cycle)
Secondary	Time of maximum observed concentration (Tmax)		Up to Cycle 7 (21 days per cycle)
Secondary	Trough concentrations (Ctrough)		Up to Cycle 7 (21 days per cycle)
Secondary	Area under the curve (AUC)		Up to Cycle 7 (21 days per cycle)
Secondary	Half-life (T1/2)		Up to Cycle 7 (21 days per cycle)
Secondary	Systemic clearance (CL)		Up to Cycle 7 (21 days per cycle)
Secondary	Volume of distribution (Vd)		Up to Cycle 7 (21 days per cycle)
Secondary	Antidrug antibody (ADA) occurrence and titer in serum (Phase 1 only)		Up to 24 months
Secondary	Investigator-assessed objective response rate (ORR) per RECIST 1.1 (Phase 1 only)		Up to 24 months
Secondary	Duration of response (DOR) (Phase 2 only)		Up to 24 months
Secondary	Disease control rate (Phase 2 only)		Up to 24 months
Secondary	Progression-free survival (PFS) (Phase 2 only)		Up to 24 months
Secondary	Overall survival (OS) (Phase 2 only)		Up to 24 months
Secondary	Incidence of treatment-emergent adverse events (Phase 2 only)		Up to 24 months
Secondary	Incidence of changes in clinical laboratory values (Phase 2 only)		Up to 24 months