Clinical trial NCT05052268: XTX202 in Patients With Advanced Solid Tumors
Official title: A First-in-Human, Multicenter, Phase 1/2, Open-Label Study of XTX202 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Lead sponsor: Xilio Development, Inc.
Sponsor class: INDUSTRY
First posted: 2021-09-22
Enrollment: 95
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: A First-in-Human, Multicenter, Phase 1/2, Open-Label Study of XTX202 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, 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities (DLTs) (Phase 1 Part 1A only)
timeFrame: 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)
measure: Incidence of treatment-emergent adverse events (Phase 1 only)
timeFrame: Up to 24 months
measure: Incidence of changes in clinical laboratory values (Phase 1 only)
timeFrame: Up to 24 months
measure: Investigator-assessed objective response rate (ORR) per RECIST 1.1 (Phase 2 only)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Plasma concentrations of XTX202 (total and intact)
timeFrame: Up to Cycle 7 (21 days per cycle)
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Up to Cycle 7 (21 days per cycle)
measure: Time of maximum observed concentration (Tmax)
timeFrame: Up to Cycle 7 (21 days per cycle)
measure: Trough concentrations (Ctrough)
timeFrame: Up to Cycle 7 (21 days per cycle)
measure: Area under the curve (AUC)
timeFrame: Up to Cycle 7 (21 days per cycle)
measure: Half-life (T1/2)
timeFrame: Up to Cycle 7 (21 days per cycle)
measure: Systemic clearance (CL)
timeFrame: Up to Cycle 7 (21 days per cycle)
measure: Volume of distribution (Vd)
timeFrame: Up to Cycle 7 (21 days per cycle)
measure: Antidrug antibody (ADA) occurrence and titer in serum (Phase 1 only)
timeFrame: Up to 24 months
measure: Investigator-assessed objective response rate (ORR) per RECIST 1.1 (Phase 1 only)
timeFrame: Up to 24 months
measure: Duration of response (DOR) (Phase 2 only)
timeFrame: Up to 24 months
measure: Disease control rate (Phase 2 only)
timeFrame: Up to 24 months
measure: Progression-free survival (PFS) (Phase 2 only)
timeFrame: Up to 24 months
measure: Overall survival (OS) (Phase 2 only)
timeFrame: Up to 24 months
measure: Incidence of treatment-emergent adverse events (Phase 2 only)
timeFrame: Up to 24 months
measure: Incidence of changes in clinical laboratory values (Phase 2 only)
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian- Newport Beach
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Paul
country: United States
facility: HealthPartners Cancer Center at Regions Hospital
state: Minnesota
city: Morristown
country: United States
facility: Atlantic Health System/Morristown Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of NJ
state: New Jersey
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center James Cancer Hospital and Solove Research Institute
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center Pavilion
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
Study officials:
References: