A Study of XB628 Alone and in Combination With Zanzalintinib in Participants With Recurrent Advanced or Metastatic Solid Tumors

A Phase 1 Dose Escalation and Expansion Study of XB628 as a Single Agent and in Combination With Zanzalintinib in Participants With Advanced or Metastatic Solid Tumors

This study consists of a Dose-Escalation stage and a Dose Expansion stage. The primary purpose of the dose escalation stage is to determine the maximum tolerated dose (MTD) and/or recommended dosage(s) for expansion (RDE[s]); and the dose expansion stage is to evaluate the preliminary antitumor activity of XB628 as a single agent and in combination with zanzalintinib.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor; Advanced Solid Tumor; Metastatic Solid Tumor; Immune Sensitive Tumor
• Intervention / Treatment: Biological: XB628; Drug: Zanzalintinib

Detailed Description

This study consists of a Dose-Escalation Stage. The Dose-Escalation Stage is designed to determine the maximum tolerated dose (MTD) and/or recommended dosage(s) for expansion (RDE[s]) of XB628 as a single agent.

• Study Type: Interventional
• Enrollment (Estimated): 303
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Exelixis Clinical Trials; Phone Number: 1-888-EXELIXIS (888-393-5494); Email: druginfo@exelixis.com
• Study Contact Backup: Name: Backup or International; Phone Number: 650-837-7400

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • Recruiting
      • Exelixis Clinical Site #5
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Exelixis Clinical Site #4
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Exelixis Clinical Site #8
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Exelixis Clinical Site #10
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Exelixis Clinical Site #11
  • Missouri
    • St Louis, Missouri, United States, 63108
      • Recruiting
      • Exelixis Clinical Site #6
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Exelixis Clinical Site #7
  • North Carolina
    • Hickory, North Carolina, United States, 28602
      • Recruiting
      • Exelixis Clinical Site #1
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Exelixis Clinical Site #3
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Exelixis Clinical Site #9
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Exelixis Clinical Site #2

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Minimum life expectancy of ≥ 12 weeks.
• Have a recurrent advanced or metastatic solid tumor that is histologically or cytologically confirmed.
• Adequate organ and marrow function.
• Not amenable to curative treatment with surgery or radiation.
• Received at least 1 line of prior systemic anticancer therapy in the recurrent or metastatic setting.
• Acceptable alternative therapy was received, refused, intolerable, or no longer effective.
• Capable of understanding and complying with the protocol requirements and provide signed informed consent according to the protocol and local requirements.

Key Exclusion Criteria

• Primary brain tumors or known active brain metastases.
• Major surgery (eg, gastrointestinal surgery, removal or biopsy of brain metastasis) within 4 weeks before the first dose of study treatment.
• Received radiation therapy within 1 week before the first dose of study treatment or clinically relevant ongoing complications from prior radiation therapy.
• Received prior therapy targeting NK cells (eg, monalizumab).
• A woman of childbearing potential has a positive serum pregnancy test within 7 days prior to study treatment.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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: Dose Escalation Phase; Participants with recurrent advanced or metastatic solid tumors will receive escalating dose levels doses of XB628 as a single agent and in combination with zanzalintinib.	Biological: XB628; Intravenous infusion(s); Drug: Zanzalintinib; Oral tablet(s); Other Names: XL092
Experimental: Dose Expansion; Participants with recurrent advanced or metastatic solid tumors will receive XB628 as a single agent and in combination with zanzalintinib.	Biological: XB628; Intravenous infusion(s); Drug: Zanzalintinib; Oral tablet(s); Other Names: XL092

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose Escalation Cohort: Number of Participants with Dose Limiting Toxicities (DLTs)	21 days
Dose Escalation Cohort: Number of Participants With Treatment Emergent Adverse Events (TEAEs)	Up to 27 months
Dose Expansion Cohort: Objective Response Rate (ORR)	Up to 27 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Area Under the Concentration-time Curve (AUC) of XB628	25 months
Maximum Plasma Concentration (Cmax) of XB628	25 months
Time to Maximum Concentration (Tmax) of XB628	25 months
Elimination Half-life (T1/2) of XB628	25 months
Apparent Clearance (CL/F) of XB628	25 months
Trough Concentration (Ctrough) of XB628	25 months
Number of Participants with Antidrug Antibody (ADA) Response to XB628	25 months
RDE for XB628	25 months
Dose Expansion Cohort: Duration of Response (DOR)	27 months
Dose Expansion Cohort: Progression-Free Survival (PFS) of XB628	27 months

Collaborators and Investigators

• Sponsor: Exelixis
• Investigators: Study Director: Medical Director, Exelixis

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2025
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: April 23, 2025
• First Submitted That Met QC Criteria: April 23, 2025
• First Posted (Actual): April 30, 2025

Study Record Updates

• Last Update Posted (Actual): June 24, 2026
• Last Update Submitted That Met QC Criteria: June 19, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: PD-L1; Solid tumor; Metastatic solid tumor; Advanced solid tumor; Zanzalintinib; XB628; Immune sensitive tumor
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis
• Other Study ID Numbers: XB628-101

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