XTX101 Monotherapy and XTX101 and Atezolizumab Combination Therapy in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a first-in-human, Phase 1/2, multicenter, open-label study designed to evaluate the safety and tolerability of XTX101 as monotherapy and XTX101 and atezolizumab combination therapy in patients with advanced solid tumors.

Detailed Description
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This is a first-in-human, Phase 1/2, multicenter, open-label study designed to evaluate the safety and tolerability of XTX101, a tumor-selective anti-CTLA-4 antibody, as monotherapy and XTX101 and atezolizumab combination therapy in patients with advanced solid tumors. Part 1A will examine XTX101 monotherapy in an accelerated and standard 3+3 dose escalation design. Based on the results of Part 1A, patients with select advanced solid tumors will be enrolled in Part 1B, which will evaluate XTX101 monotherapy in relation to specific PD biomarkers. Part 1C will examine XTX101 in combination with atezolizumab in a standard 3+3 dose escalation/dose de-escalation design.

Official Title
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A First-in-Human, Multicenter, Phase 1/2, Open-Label Study of XTX101 Monotherapy and XTX101 and Atezolizumab Combination Therapy in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: XTX101
* Drug: Atezolizumab
* Drug: XTX101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Disease Criteria - Part 1A and 1C: 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; Part 1B: Any histologically or cytologically confirmed solid tumor malignancy for which anti-PD-1 or anti-PD-L1 treatment is approved and has progressed on or after prior anti-PD-1 or anti-PD-L1 therapy. Patients with metastatic castrate-resistant prostate cancer if they have progressed on at least 2 lines of systemic therapy Patients with extensive stage small cell lung cancer (SCLC) after at least 1 line of prior therapy Patients with microsatellite stable colorectal cancer after at least 2 lines of prior therapy ECOG performance status of 0 or 1 Adequate organ function Part 1B and Part 1C only: measurable disease per iRECIST Exclusion Criteria: Received prior treatment with anti-CTLA-4 therapy Received prior immune-checkpoint therapy and experienced Grade 3 or greater toxicity lasting greater than 6 weeks Received prior systemic anticancer therapy within 4 weeks prior to study treatment Received prior radiotherapy within 2 weeks prior to study treatment Has a diagnosis of immunodeficiency Has known malignancy (other than disease under study) that is progressing or has required active treatment within the past 3 years 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 intravenous therapy within 4 weeks prior to study treatment, or oral therapy within 2 weeks prior to study treatment Has a history of severe hypersensitivity reaction (≥ Grade 3) to any study intervention and/or any of its excipients Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study

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: Part 1A - XTX101 Monotherapy Dose Escalation<br>Part 1A Dose Escalation of XTX101 administered in ascending doses to patients with advanced or metastatic solid tumors to find the recommended phase 2 dose (RP2D). | Drug: XTX101<br>* XTX101 monotherapy<br>|
| Experimental: Part 1B - Pharmacodynamic (PD) Dose Expansion<br>Part 1B XTX101 at the RP2D will be administered to further examine XTX101 as monotherapy in patients with select advanced solid tumors. | Drug: XTX101<br>* XTX101 monotherapy<br>|
| Experimental: Part 1C - XTX101 Dose Escalation in Combination with Atezolizumab<br>Part 1C will receive a labeled dose of atezolizumab in combination with XTX101. | Drug: Atezolizumab<br>* 1200 mg administered every 3 weeks in combination with XTX101<br>Drug: XTX101<br>* In combination with Atezolizumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 at Cycle 2 day 1 (approximately 3 weeks) | 
| Incidence of Dose Limiting Toxicities (DLTs) in Part 1C |  | Cycle 1 Day 1 up to Cycle 3 Day 1 (approximately 6 weeks) | 
| Incidence of treatment-emergent adverse events |  | Up to 24 months | 
| Incidence of changes in clinical laboratory abnormalities |  | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-assessed objective response rate (ORR) per iRECIST |  | Up to 24 months | 
| Antidrug antibody (ADA) occurrence and titer in serum |  | Up to 24 months | 
| Plasma concentrations of XTX101 (total and intact) |  | Up to Cycle 8 (21 days per cycle) | 
| Maximum observed plasma concentration (Cmax) |  | Up to Cycle 8 (21 days per cycle) | 
| Time of maximum observed concentration (Tmax) |  | Up to Cycle 8 (21 days per cycle) | 
| Trough concentrations (Ctrough) |  | Up to Cycle 8 (21 days per cycle) | 
| Area under the curve (AUC) |  | Up to Cycle 8 (21 days per cycle) | 
| Half-life (T1/2) |  | Up to Cycle 8 (21 days per cycle) | 
| Systemic clearance (CL) |  | Up to Cycle 8 (21 days per cycle) | 
| Volume of distribution (Vd) |  | Up to Cycle 8 (21 days per cycle) |