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
Trial Snapshot
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- Xilio Development, Inc.
- Enrollment
- 140
- Primary Endpoint
- Incidence of Dose Limiting Toxicities (DLTs) in Part 1A
Study Overview
Brief Summary
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.
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 Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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/
- •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.
Outcomes
Primary Outcomes
Incidence of Dose Limiting Toxicities (DLTs) in Part 1A
Time Frame: 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)
Time Frame: Up to Safety Follow Up Period (90 [+7] days after the last dose)
Incidence of serious adverse events (Phase 1 and Phase 2)
Time Frame: 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)
Time Frame: 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)
Time Frame: Up to Safety Follow Up Period (90 [+7] days after the last dose)
Secondary Outcomes
- 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))