Trial Title:
XTX301 in Patients with Advanced Solid Tumors
NCT ID:
NCT05684965
Condition:
Advanced Solid Tumor
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
XTX301
Description:
XTX301 monotherapy
Arm group label:
Phase 1 - XTX301 Monotherapy Dose Escalation and Pharmacodynamics Expansion
Arm group label:
Phase 2 - XTX301 Monotherapy Dose Expansion in Disease-Specific Cohorts
Summary:
This is a first-in-human, multicenter, Phase 1/2, open-label study designed to evaluate
the safety and tolerability of XTX301 as monotherapy in patients with advanced solid
tumors.
Detailed description:
This is a first-in-human, multicenter, Phase 1/2, open-label study designed to evaluate
the safety, tolerability, PK, PD, immunogenicity, and antitumor activity/efficacy of
XTX301, a tumor-activated interleukin-12, as monotherapy in patients with advanced solid
tumors.
Phase 1. Part 1A will examine XTX301 monotherapy in a 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 XTX301 monotherapy in relation to specific PD
biomarkers.
Phase 2 will further evaluate the safety and antitumor activity/efficacy of XTX301
monotherapy in disease-specific expansion cohorts of patients with select tumors, namely:
head and neck squamous cell carcinoma (HNSCC), melanoma, non-small cell lung cancer
(NSCLC), ovarian cancer, castrate-resistant prostate cancer (CRPC), triple-negative
breast cancer (TNBC)
Criteria for eligibility:
Criteria:
Inclusion Criteria:
• Disease Criteria: Part 1A - Any histologically or cytologically confirmed solid tumor
malignancy that is locally advanced or metastatic and has failed standard therapy,
standard therapy does not confer survival benefit, or standard therapy is not available.
Part 1B- Any histologically or cytologically confirmed solid tumor malignancy among the
tumor types outlined below, that is locally advanced or metastatic and has failed
standard therapy, standard therapy does not confer survival benefit, or standard therapy
is not available. Patients with the following tumor types are eligible for Part 1B:
melanoma, NSCLC, HNSCC, TNBC, cervical cancer, microsatellite instability high/mismatch
repair deficient (MSI-H/dMMR) colorectal cancer, or MSI-H/dMMR endometrial cancer. Note:
Based on evolving internal and external data, the Sponsor may decide to open a "backfill
cohort" in Part 1B for patients with any of the following solid tumors: prostate cancer,
ovarian cancer, pancreatic cancer, microsatellite stable colorectal cancer, T-cell
lymphoma.
Phase 2 - All patients must have measurable disease at baseline per RECIST 1.1.
Additional disease-specific criteria per cohort are as follows:
i. Cohort 2A: head and neck squamous cell carcinoma (HNSCC). Must have histologically or
cytologically confirmed locally recurrent or metastatic HNSCC previously treated with 1
to 2 lines of therapy. Unless contraindicated, prior therapy must have included
PD-1/PD-L1 inhibitor and/or platinum-based chemotherapy per local and institutional
standard of care.
ii. Cohort 2B: melanoma. Must have unresectable or metastatic melanoma previously treated
with 1 to 2 lines of therapy in the recurrent or metastatic setting. Unless
contraindicated, prior therapy must have included a PD-1/PD-L1 inhibitor alone or in
combination. Patients with known BRAF V600-activating mutation must have previously
received targeted therapy per local and institutional standard of care.
iii. Cohort 2C: non-small cell lung cancer (NSCLC). Must have histologically confirmed
locally advanced or metastatic NSCLC previously treated with 1 to 2 lines of therapy.
Unless contraindicated, prior therapy must have included a PD1/PD-L1 inhibitor and a
platinum-based regimen, given either concurrently or separately per local and
institutional standard of care. Patients with known genomic alteration for which a
targeted therapy is approved (e.g. ROS1 fusion, NTRK fusion, BRAF V600E mutation, EGFR
mutation, or ALK fusion) must have been previously treated with relevant targeted therapy
per local and institutional standard of care.
iv. Cohort 2D: ovarian cancer. Must have histologically confirmed epithelial ovarian
cancer, fallopian tube cancer, or primary peritoneal cancer with current
platinum-resistant disease per investigator's assessment (e.g. patient is not eligible
for further platinum-containing treatment). Patients must have previously experienced a
response lasting at least 180 days to first-line platinum-based therapy. Patients who
have been unable to tolerate platinum therapy are also eligible. Unless contraindicated,
patients with known BRCA mutation must have received a poly(ADP-ribose) polymerase (PARP)
inhibitor.
v. Cohort 2E: castrate-resistant prostate cancer (CRPC). Must have metastatic CRPC
previously treated with an androgen receptor pathway inhibitor (e.g. abiraterone,
enzalutamide, darolutamide, or apalutamide) and/or chemotherapy per local and
institutional standard of care. Baseline testosterone must be ≤ 50 ng/dL (≤ 2.0 nM), and
surgical or ongoing medical castration must be maintained throughout the duration of the
study.
vi. Cohort 2F: triple-negative breast cancer (TNBC). Must have metastatic TNBC with
disease relapse after 2 to 4 previous lines of therapy per local and institutional
standard of care. Neoadjuvant and/or adjuvant chemotherapy will count as 1 prior line of
therapy. Unless contraindicated, patients with known actionable mutations (e.g. BRCA1 or
BRCA2) must have received prior therapy with the corresponding targeted agent per local
and institutional standard of care
- ECOG performance status of 0-2
- Adequate organ function
- Tumor tissue samples: Part 1B: patients must have lesions amenable to biopsy and be
willing and able to provide fresh tumor biopsies before and after initiation of
treatment
- Patients with recent major surgery must have adequately recovered with no ongoing
complications from the surgery before receiving study drug
Exclusion Criteria:
- Prior treatment with IL-12 therapy (any form, e.g. recombinant human, prodrug,
intratumoral, etc.)
- Known liver metastasis based on imaging
- Possible area of ongoing necrosis (non-disease-related), such as active ulcer,
nonhealing wound, or intercurrent bone fracture
- Active primary central nervous system (CNS) malignancy, CNS metastases, and/or
carcinomatous meningitis
- Active autoimmune disease
- History of Grade ≥ 3 immune-related adverse events associated with prior
immunotherapy unless these were adequately resolved with therapy within 14 days
- A diagnosis of immunodeficiency; receiving chronic systemic therapy exceeding
prednisone 10 mg daily or equivalent or any other form of immunosuppressive therapy
within 7 days before the first dose of study drug
- Active hepatitis B or active hepatitis C infection
- Prior treatment with gene therapy, organ transplant, or hematopoietic stem-cell
transplant
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of California, Davis Comprehensive Cancer Center
Address:
City:
Sacramento
Zip:
95817
Country:
United States
Status:
Recruiting
Contact:
Last name:
Frances Lara
Phone:
916-734-8134
Email:
fnlara@ucdavis.edu
Facility:
Name:
Yale Cancer Center
Address:
City:
New Haven
Zip:
06510
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jialing Zhang, PhD
Phone:
475-234-9684
Email:
jialing.zhang@yale.edu
Facility:
Name:
HealthPartners Frauenshuh Cancer center
Address:
City:
St. Louis Park
Zip:
55426
Country:
United States
Status:
Recruiting
Contact:
Last name:
Alissa Gavenda
Phone:
952-993-6705
Email:
alissa.gavenda@parknicollet.com
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jessica Ley
Phone:
314-747-8092
Email:
jcley@wustl.edu
Facility:
Name:
Hackensack University Medical Center
Address:
City:
Hackensack
Zip:
07601
Country:
United States
Status:
Recruiting
Contact:
Last name:
Min Zhu
Phone:
551-996-3953
Email:
Min.Zhu@hmhn.org
Facility:
Name:
The Gabrail Pharmacology Phase 1 Research Center
Address:
City:
Canton
Zip:
44718
Country:
United States
Status:
Recruiting
Contact:
Last name:
Carrie Smith, RN
Phone:
330-417-8231
Email:
csmith@gabrailcancercenter.com
Facility:
Name:
University Hospital Cleveland Medical Center
Address:
City:
Cleveland
Zip:
44106
Country:
United States
Status:
Recruiting
Contact:
Last name:
Amit Mahipal, MD
Email:
amit.mahipal@uhhospitals.org
Facility:
Name:
The Ohio State University Wexner Medical Center
Address:
City:
Columbus
Zip:
43221
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jacob Nelson
Email:
Jacob.nelson@osumc.edu
Facility:
Name:
University of Pittsburgh Medical Center-Hillman Cancer Center
Address:
City:
Pittsburgh
Zip:
15232
Country:
United States
Status:
Recruiting
Contact:
Last name:
Julie Urban
Phone:
412-623-7396
Email:
urbanj2@upmc.edu
Facility:
Name:
Tranquil Clinical Research
Address:
City:
Webster
Zip:
77598
Country:
United States
Status:
Recruiting
Contact:
Last name:
Amber Christian
Phone:
713-907-6054
Email:
amberc@tranquilityresearch.com
Facility:
Name:
Medical College of Wisconsin
Address:
City:
Milwaukee
Zip:
53226
Country:
United States
Status:
Recruiting
Contact:
Last name:
Medical College of Wisconsin CCCTO
Phone:
414-805-8900
Email:
cccto@mcw.edu
Start date:
May 11, 2023
Completion date:
February 2027
Lead sponsor:
Agency:
Xilio Development, Inc.
Agency class:
Industry
Source:
Xilio Development, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05684965
