An Open-Label Dose-Escalation Study to Evaluate XmAb24306 as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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This study will evaluate the safety, tolerability, pharmacokinetics, and activity of XmAb24306 alone or in combination with a checkpoint inhibitor treatment in participants with locally advanced or metastatic solid tumors.

Official Title
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A Phase Ia/Ib, Open-Label, Multicenter, Global, Dose-Escalation Study to Evaluate the Safety and Pharmacokinetics of XmAb24306 as a Single Agent and in Combination With Atezolizumab in Patients With Locally Advanced or Metastatic Solid Tumors

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: XmAb24306
* Drug: Atezolizumab
* Drug: XmAb24306


Participation Criteria
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Eligibility Criteria
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Key General Inclusion Criteria Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Life expectancy >/= 12 weeks Adequate hematologic and end-organ function For participants receiving therapeutic anticoagulation: stable anticoagulant regimen Negative serum pregnancy test for women of childbearing potential Histologically confirmed locally advanced, recurrent, or metastatic incurable solid tumor malignancy Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Availability of representative tumor specimens Key General Exclusion Criteria Pregnant or breastfeeding, or intending to become pregnant during the study Significant cardiovascular disease Current treatment with medications that prolong the QT interval Known clinically significant liver disease Poorly controlled Type 2 diabetes mellitus Symptomatic, untreated, or actively progressing CNS metastases History of leptomeningeal disease History of malignancy other than disease under study within 3 years prior to screening Active or history of autoimmune disease or immune deficiency Active tuberculosis, hepatitis B, hepatitis C, or known/suspected Epstein Barr virus infection Positive for HIV infection Prior allogeneic stem cell or solid organ transplantation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1a Dose Escalation<br>Participants will receive XmAb24306 until study treatment discontinuation or study termination. | Drug: XmAb24306<br>* Participants will receive intravenous (IV) XmAb24306.<br>* Other names: RO7310729;|
| Experimental: Phase 1a Dose Expansion<br>Participants will receive XmAb24306 until study treatment discontinuation or study termination. | Drug: XmAb24306<br>* Participants will receive intravenous (IV) XmAb24306.<br>* Other names: RO7310729;|
| Experimental: Phase 1b Dose Escalation<br>Participants will receive XmAb24306 and atezolizumab until study treatment discontinuation or study termination. | Drug: Atezolizumab<br>* Participants will receive IV XmAb24306 followed by IV atezolizumab<br>* Other names: RO5541267;Drug: XmAb24306<br>* Participants will receive IV XmAb24306 followed by IV atezolizumab.<br>* Other names: RO7310729;|
| Experimental: Phase 1b Dose Expansion<br>Participants will receive XmAb24306 and atezolizumab until study treatment discontinuation or study termination. | Drug: Atezolizumab<br>* Participants will receive IV XmAb24306 followed by IV atezolizumab<br>* Other names: RO5541267;Drug: XmAb24306<br>* Participants will receive IV XmAb24306 followed by IV atezolizumab.<br>* Other names: RO7310729;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Adverse Events |  | Up to approximately 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Concentration of XmAb24306 |  | Baseline, then at pre-defined intervals for the first year of treatment or until participant discontinues study treatment | 
| Objective Response Rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |  | Up to approximately 4 years | 
| Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1 |  | Up to approximately 4 years | 
| Progression-Free Survival (PFS) as Determined by the Investigator According to RECIST v1.1 |  | Up to approximately 4 years | 
| ORR as Based on Radiographic Assessment by the Investigator Using Modified RECIST v1.1 for Immune-Based Therapeutics (iRECIST) |  | Up to approximately 4 years | 
| DOR as Based on Radiographic Assessment by the Investigator Using iRECIST |  | Up to approximately 4 years | 
| PFS as Based on Radiographic Assessment by the Investigator Using iRECIST |  | Up to approximately 4 years | 
| Overall Survival (OS) |  | Up to approximately 4 years |