XTX202 in Patients With Advanced Solid Tumors
Study Details
Study Description
Brief Summary
A First-in-Human, Multicenter, Phase 1/2, Open-Label Study of XTX202 in Patients with Advanced Solid Tumors
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1/Phase 2 |
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 will examine XTX202 monotherapy in an accelerated and standard 3+3 dose-escalation design. Based on the results of Phase 1, patients with select advanced solid tumors will be enrolled in Phase 2.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Phase 1 XTX202 Dose Escalation Phase 1 Dose Escalation of XTX202 administered in ascending doses to patients with advanced or metastatic solid tumors to find the recommended phase 2 dose (RP2D). |
Drug: XTX202
XTX202 Monotherapy
|
Experimental: Phase 2 XTX202 Dose Expansion Part 2A will enroll patients with metastatic renal cell carcinoma who have progressed following standard-of-care treatment. Part 2B will enroll patients with melanoma who have progressed following standard-of-care treatment. |
Drug: XTX202
XTX202 Monotherapy
|
Outcome Measures
Primary Outcome Measures
- Incidence of Dose Limiting Toxicities (DLTs) (Phase 1 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)]
- Incidence of treatment-emergent adverse events (Phase 1 only) [Up to 24 months]
- Incidence of changes in clinical laboratory values (Phase 1 only) [Up to 24 months]
- Investigator-assessed objective response rate (ORR) per RECIST 1.1 (Phase 2 only) [Up to 24 months]
Secondary Outcome Measures
- Plasma concentrations of XTX202 (total and intact) [Up to Cycle 7 (21 days per cycle)]
- Maximum observed plasma concentration (Cmax) [Up to Cycle 7 (21 days per cycle)]
- Time of maximum observed concentration (Tmax) [Up to Cycle 7 (21 days per cycle)]
- Trough concentrations (Ctrough) [Up to Cycle 7 (21 days per cycle)]
- Area under the curve (AUC) [Up to Cycle 7 (21 days per cycle)]
- Half-life (T1/2) [Up to Cycle 7 (21 days per cycle)]
- Systemic clearance (CL) [Up to Cycle 7 (21 days per cycle)]
- Volume of distribution (Vd) [Up to Cycle 7 (21 days per cycle)]
- Antidrug antibody (ADA) occurrence and titer in serum (Phase 1 only) [Up to 24 months]
- Investigator-assessed objective response rate (ORR) per RECIST 1.1 (Phase 1 only) [Up to 24 months]
- Duration of response (DOR) (Phase 2 only) [Up to 24 months]
- Disease control rate (Phase 2 only) [Up to 24 months]
- Progression-free survival (PFS) (Phase 2 only) [Up to 24 months]
- Overall survival (OS) (Phase 2 only) [Up to 24 months]
- Incidence of treatment-emergent adverse events (Phase 2 only) [Up to 24 months]
- Incidence of changes in clinical laboratory values (Phase 2 only) [Up to 24 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Disease Criteria - Phase 1: 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 2, Part 2a: Patients with metastatic RCC who have previously been treated with an approved anti-PD-1 and a TKI. 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 an approved anti-PD-1 and an anti-CTLA4 checkpoint inhibitor
-
ECOG performance status of 0 or 1
-
Adequate organ function
Exclusion Criteria:
-
Received prior treatment with IL-2 therapy
-
History of clinically significant pulmonary disease
-
History of clinically significant cardiovascular disease
-
Has a diagnosis of immunodeficiency
-
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 therapy within 4 weeks prior to study treatment
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
2 | HealthPartners Cancer Center at Regions Hospital | Saint Paul | Minnesota | United States | 55101 |
3 | Carolina BioOncology Institute | Huntersville | North Carolina | United States | 28078 |
4 | The Ohio State University Wexner Medical Center James Cancer Hospital and Solove Research Institute | Columbus | Ohio | United States | 43210 |
5 | Sarah Cannon Research Institute | Nashville | Tennessee | United States | 37203 |
Sponsors and Collaborators
- Xilio Development, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- XTX202-01/02-001