XTX501 in Patients With Metastatic Non-Small Cell Lung Cancer and Advanced Solid Tumors

A First-in-Human, Multicenter, Phase 1/2, Open-Label Study of XTX501 in Participants With Metastatic Non-Small Cell Lung Cancer and Advanced Solid Tumors

This is a first-in-human, multicenter, Phase 1/2, open-label study designed to evaluate the safety and tolerability of XTX501 as monotherapy in participants with metastatic non-small cell lung cancer (NSCLC) and select advanced solid tumors.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Solid Tumor; Metastatic NSCLC - Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: XTX501

Detailed Description

This is a first-in-human, Phase 1/2, multicenter, open-label study designed to evaluate the safety, tolerability, PK, pharmacodynamics, immunogenicity, and antitumor activity of XTX501, an investigational bispecific PD-1/masked IL-2 in participants with metastatic NSCLC and select advanced solid tumors.

Phase 1, Part 1A will examine XTX501 monotherapy in a Bayesian Optimal Interval design to determine the maximum tolerated dose up to 10 dose regimens.

Phase 1, Part 1B will further evaluate the safety and antitumor activity of XTX501 at dose regimens under consideration for the recommended Phase 2 dose(s).

Phase 2 will further evaluate the efficacy of the selected recommended Phase 2 dose(s).

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Xilio Medical Affairs; Phone Number: (857) 524-2466; Email: medicalaffairs@xiliotx.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Measurable disease at baseline per RECIST v1.1
• ECOG performance status of 0 or 1
• Adequate organ function

• Metastatic NSCLC:

  • Must have histologically confirmed metastatic NSCLC.
  • Tumor must have been assessed for EGFR and ALK per local standard of practice; patients with these driver mutations are excluded.
  • Patients with tumors known to have the following alterations are excluded: ROS1, RET, MET, HER-2, NTRK 1/2/3.
  • Patients must have previously derived clinical benefit from a PD-1/PD-L1 inhibitor or PD-1/PDL-1 bispecific without progression for at least 6 months.

Exclusion Criteria:

• Prior treatment with IL-2
• History of significant pulmonary disease
• History of clinically significant cardiovascular disease
• Active CNS metastases
• Pregnant or breastfeeding

In Phase 1, participants with select additional solid tumor types may be enrolled.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 - XTX501 Monotherapy Dose Escalation and Backfill; Part 1A will examine XTX501 monotherapy in a Bayesian Optimal Interval design to determine the maximum tolerated dose up to 10 dose regimens. Part 1B will further evaluate the safety and antitumor activity of XTX501 at dose regimens under consideration for the recommended Phase 2 dose(s).	Drug: XTX501; XTX501 monotherapy
Experimental: Phase 2- XTX501 Monotherapy Dose Expansion in metastatic NSCLC; Phase 2 will further evaluate the efficacy of the selected recommended Phase 2 dose(s) in participants with metastatic NSCLC.	Drug: XTX501; XTX501 monotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Dose Limiting Toxicities (DLTs) in Part 1A	Cycle 1 Day 1 up to just prior to the second dose of study drug (approximately 21 days)
Incidence of treatment-emergent adverse events (Phase 1 and Phase 2)	Up to Safety Follow Up Period (90 [+7] days after the last dose)
Incidence of serious adverse events (Phase 1 and Phase 2)	Up to Safety Follow Up Period (90 [+7] days after the last dose)
Incidence of significant change from baseline in clinical laboratory values (Phase 1 and Phase 2)	Up to Safety Follow Up Period (90 [+7] days after the last dose)
Investigator-assessed objective response rate (ORR) per RECIST v1.1 (Phase 2)	Up to Safety Follow Up Period (90 [+7] days after the last dose)

Secondary Outcome Measures

Outcome Measure	Time Frame
Investigator-assessed objective response rate (ORR) per RECIST v1.1 (Phase 1)	Up to Safety Follow Up Period (90 [+7] days after the last dose)
Investigator-assessed duration of response (DOR) per RECIST v1.1 (Phase 1 and Phase 2)	Up to Safety Follow Up Period (90 [+7] days after the last dose)
Investigator-assessed disease control rate (DCR) per RECIST v1.1 (Phase 2)	Up to Safety Follow Up Period (90 [+7] days after the last dose)
Investigator-assessed progression free survival (PFS) per RECIST v1.1 (Phase 2)	Up to Safety Follow Up Period (90 [+7] days after the last dose)
Incidence and persistence of antidrug antibodies (ADAs) (Phase 1 and Phase 2)	Up to End of Treatment (within 10 days of the decision to discontinue XTX501)
Maximum observed plasma concentration (Cmax) (Phase 1 and Phase 2)	Up to End of Treatment (within 10 days of the decision to discontinue XTX501)
Time of maximum observed concentration (Tmax) (Phase 1 and Phase 2)	Up to End of Treatment (within 10 days of the decision to discontinue XTX501)
Trough concentrations (Ctrough) (Phase 1 and Phase 2)	Up to End of Treatment (within 10 days of the decision to discontinue XTX501)
Area under the curve (AUC) (Phase 1 and Phase 2)	Up to End of Treatment (within 10 days of the decision to discontinue XTX501)
Half-life (t1/2) (Phase 1 and Phase 2)	Up to End of Treatment (within 10 days of the decision to discontinue XTX501)
Systemic clearance (CL) (Phase 1 and Phase 2)	Up to End of Treatment (within 10 days of the decision to discontinue XTX501)
Volume of distribution (Vd) (Phase 1 and Phase 2)	Up to End of Treatment (within 10 days of the decision to discontinue XTX501)

Collaborators and Investigators

• Sponsor: Xilio Development, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): November 1, 2029

Study Registration Dates

• First Submitted: June 22, 2026
• First Submitted That Met QC Criteria: June 30, 2026
• First Posted (Actual): July 7, 2026

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: June 30, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: XTX501-01/02-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No