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

Sponsor
Xilio Development, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04896697
Collaborator
Merck Sharp & Dohme LLC (Industry)
144
10
4
54.5
14.4
0.3

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

Study Type:
Interventional
Anticipated Enrollment :
144 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A First-in-Human, Multicenter, Phase 1/2, Open-Label Study of XTX101 Monotherapy and XTX101 and Pembrolizumab Combination Therapy in Patients With Advanced Solid Tumors
Actual Study Start Date :
Sep 13, 2021
Anticipated Primary Completion Date :
Mar 30, 2026
Anticipated Study Completion Date :
Mar 30, 2026

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

  1. 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)]

  2. Incidence of treatment-emergent adverse events and changes in clinical laboratory abnormalities (Part 1A, 1B & 1C only) [Up to 24 months]

  3. Incidence changes in clinical laboratory (Part 1A, 1B & 1C only) [Up to 24 months]

  4. Investigator-assessed objective response rate (ORR) per iRECIST (Part 2 only) [Up to 24 months]

Secondary Outcome Measures

  1. Investigator-assessed objective response rate (ORR) per iRECIST (Part 1A, 1B & 1C only) [Up to 24 months]

  2. Antidrug antibody (ADA) occurrence and titer in serum (Part 1A, 1B & 1C only) [Up to 24 months]

  3. Plasma concentrations of XTX101 (total and intact) [Up to Cycle 7 (21 days per cycle)]

  4. Maximum observed plasma concentration (Cmax) [Up to Cycle 7 (21 days per cycle)]

  5. Time of maximum observed concentration (Tmax) [Up to Cycle 7 (21 days per cycle)]

  6. Trough concentrations (Ctrough) [Up to Cycle 7 (21 days per cycle)]

  7. Area under the curve (AUC) [Up to Cycle 7 (21 days per cycle)]

  8. Half-life (T1/2) [Up to Cycle 7 (21 days per cycle)]

  9. Systemic clearance (CL) [Up to Cycle 7 (21 days per cycle)]

  10. Volume of distribution (Vd) [Up to Cycle 7 (21 days per cycle)]

  11. Duration of response (Part 2 only) [Up to 24 months]

    Time from first documented confirmed response to first documented disease progression

  12. 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

  13. Progression-free survival (Part 2 only) [Up to 24 months]

    Time from first dose to first documented disease progression or death

  14. Overall survival (Part 2 only) [Up to 24 months]

    Time from first dose to death due to any cause

  15. Incidence of treatment-emergent adverse events and changes in clinical laboratory abnormalities (Part 2 only) [Up to 24 months]

  16. Incidence changes in clinical laboratory (Part 2 only) [Up to 24 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Responsible Party:
Xilio Development, Inc.
ClinicalTrials.gov Identifier:
NCT04896697
Other Study ID Numbers:
  • XTX101-01/02-001
First Posted:
May 21, 2021
Last Update Posted:
Jul 1, 2022
Last Verified:
Jun 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 1, 2022