XTX101 Monotherapy and XTX101 and Pembrolizumab Combination Therapy in Patients With Advanced Solid Tumors
Study Details
Study Description
Brief Summary
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 pembrolizumab combination therapy in patients with advanced solid tumors.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1/Phase 2 |
Detailed Description
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 pembrolizumab 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 pembrolizumab in a standard 3+3 dose escalation design, examining up to 2 dose levels of XTX101 in combination with the labeled dose of pembrolizumab. After completion of Part 1C, the study will initiate Part 2, examining the RP2D of XTX101 and pembrolizumab combination therapy in patients with unresectable or metastatic melanoma.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Part 1A - XTX101 Monotherapy Dose Escalation 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
XTX101 monotherapy
|
Experimental: Part 1B - Pharmacodynamic (PD) Dose Expansion Part 1B XTX101 at the RP2D will be administered to further examine XTX101 as monotherapy in patients with select advanced solid tumors. |
Drug: XTX101
XTX101 monotherapy
|
Experimental: Part 1C - XTX101 Dose Escalation in Combination with Pembrolizumab Part 1C Standard labeled dose of pembrolizumab followed by administration of escalating doses of XTX101 to patients with advanced or metastatic solid tumors to find the recommended phase 2 dose (RP2D). |
Drug: Pembrolizumab
200 mg administered every 3 weeks in combination with XTX101
Drug: XTX101
In combination with Pembrolizumab
|
Experimental: Part 2- XTX101 and Pembrolizumab Combination Therapy Part 2 will examine XTX101 and pembrolizumab combination therapy at the RP2D in patients with unresectable or metastatic melanoma |
Drug: Pembrolizumab
200 mg administered every 3 weeks in combination with XTX101
Drug: XTX101
In combination with Pembrolizumab
|
Outcome Measures
Primary Outcome Measures
- Incidence of Dose Limiting Toxicities (DLTs) (Part 1A and Part 1C only) [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 treatment-emergent adverse events and changes in clinical laboratory abnormalities (Part 1A, 1B & 1C only) [Up to 24 months]
- Incidence changes in clinical laboratory (Part 1A, 1B & 1C only) [Up to 24 months]
- Investigator-assessed objective response rate (ORR) per iRECIST (Part 2 only) [Up to 24 months]
Secondary Outcome Measures
- Investigator-assessed objective response rate (ORR) per iRECIST (Part 1A, 1B & 1C only) [Up to 24 months]
- Antidrug antibody (ADA) occurrence and titer in serum (Part 1A, 1B & 1C only) [Up to 24 months]
- Plasma concentrations of XTX101 (total and intact) [Up to Cycle 7 (21 days per cycle)]
- Maximum observed plasma concentration (Cmax) [Up to Cycle 7 (21 days per cycle)]
- Time of maximum observed concentration (Tmax) [Up to Cycle 7 (21 days per cycle)]
- Trough concentrations (Ctrough) [Up to Cycle 7 (21 days per cycle)]
- Area under the curve (AUC) [Up to Cycle 7 (21 days per cycle)]
- Half-life (T1/2) [Up to Cycle 7 (21 days per cycle)]
- Systemic clearance (CL) [Up to Cycle 7 (21 days per cycle)]
- Volume of distribution (Vd) [Up to Cycle 7 (21 days per cycle)]
- Duration of response (Part 2 only) [Up to 24 months]
Time from first documented confirmed response to first documented disease progression
- Disease control rate (Part 2 only) [Up to 18 weeks]
Percent of patients who achieve iCR, partial response per iRECIST (iPR), or stable disease per iRECIST (iSD) at 18 weeks
- Progression-free survival (Part 2 only) [Up to 24 months]
Time from first dose to first documented disease progression or death
- Overall survival (Part 2 only) [Up to 24 months]
Time from first dose to death due to any cause
- Incidence of treatment-emergent adverse events and changes in clinical laboratory abnormalities (Part 2 only) [Up to 24 months]
- Incidence changes in clinical laboratory (Part 2 only) [Up to 24 months]
Eligibility Criteria
Criteria
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. Part 2- histologically or cytologically confirmed unresectable or metastatic melanoma that has not been treated with prior anti-PD-1 or anti-PD-L1 therapy
-
ECOG performance status of 0 or 1
-
Adequate organ function
-
Part 2 only: measurable disease per iRECIST
Exclusion Criteria:
-
Received prior treatment with anti-CTL-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 therapy within 4 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
-
Part 2 only: has ocular melanoma
-
Part 2 only: has received prior anti-PD-1/L-1 therapy
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | California Cancer Associates for Research and Excellence, cCARE | Encinitas | California | United States | 92024 |
2 | California Cancer Associates for Research and Excellence, cCARE | San Marcos | California | United States | 92069 |
3 | Sarah Cannon Research Institute at Florida Cancer Specialists | Orlando | Florida | United States | 32827 |
4 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
5 | Carolina BioOncology Institute | Huntersville | North Carolina | United States | 28078 |
6 | University of Pittsburgh Medical Center- Hillman Cancer Center | Pittsburgh | Pennsylvania | United States | 15232 |
7 | Next Oncology | Austin | Texas | United States | 78758 |
8 | Mary Crowley Cancer Research | Dallas | Texas | United States | 75230 |
9 | Tranquil Clinical Research | Webster | Texas | United States | 77598 |
10 | NEXT Virginia | Fairfax | Virginia | United States | 22031 |
Sponsors and Collaborators
- Xilio Development, Inc.
- Merck Sharp & Dohme LLC
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- XTX101-01/02-001