Trial Title:
Efficacy and Safety Study of OMTX705, Monotherapy and Pembrolizumab-combined, in Subjects With Advanced Solid Tumors.
NCT ID:
NCT05547321
Condition:
Advanced Solid Tumor
Conditions: Official terms:
Neoplasms
Pembrolizumab
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Other
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
OMTX705
Description:
The investigational product is OMTX705 administered as monotherapy.
Arm group label:
Combination (OMTX705 + pembrolizumab)
Arm group label:
Monotherapy (OMTX705)
Other name:
NA at this moment
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
The investigational product is OMTX705 administered in combination with pembrolizumab.
Arm group label:
Combination (OMTX705 + pembrolizumab)
Other name:
Keytruda (trademark)
Summary:
Open-label, two parallel arm, multicenter, Phase 1 dose-escalation study to evaluate the
safety and tolerability of OMTX705, both as monotherapy or in combination with
pembrolizumab in the treatment of patients with advanced or metastatic cancer in whom
there is no available standard therapeutic option.
Detailed description:
The study consists of 2 parts:
- Part 1: Phase 1 dose-escalation with 2 parallel staggered escalation cohorts: one
cohort of patients treated with OMTX705 as monotherapy and one cohort of patients
receiving escalating doses of OMTX705 in combination with standard pembrolizumab.
The combination arm will start once OMTX705 monotherapy safety has been evaluated.
- Part 2: Up to 4 cohort expansions to confirm the safety of OMTX705 as monotherapy
and in combination with pembrolizumab and will provide additional efficacy
information.
The classical 3+3 design will be followed to establish the maximum tolerated dose (MTD)
or the provisional recommended dose for the expansion phase. Three to six patients per
treatment cohort will be assigned to receive sequentially higher doses of OMTX705 on Days
1 and 8 in cycles of 21 days. The OMTX705 starting dose is 1.0 mg/kg
Dose escalation will be based on a review of all parameters critical to subject safety
from C1D1 to the start of C2D1. A safety report will be reviewed by the safty review
committee (SRC) to determine if progression to the next planned dose level should occur
or if additional subjects or lower dose levels are needed.
Expansion phase (Part 2): Once MTD is identified, or if another dose is identified
because observed efficacy, non-DLT safety, or because a dose is supported by the PK/PD
model under development, a provisional recommended Phase 2 dose (RP2D) will be selected
by the sponsor and SRC for cohort expansion. Up to 4 cohort expansions of up to 15
patients each will proceed to confirm the safety and for initial assessment of anti-tumor
activity. Each expansion cohort can be enriched with patients with advanced/metastatic
cancer with no therapeutic standard alternative indications in which antitumor activity
has been observed during the escalation phase. The final decision on the expansion cohort
enrichment will be made by the sponsor with the support of the SRC.
After treatment discontinuation, patients will have the EoT visit 30 (±2) days after the
last dose of any component of the treatment for the evaluation of new AEs or recovery
from previous ones. EoT visit can be anticipated for patients scheduled to receive the
next line of systemic treatment to the day of the start of the new therapy if this
happens less than 30 days after the last dose of study treatment.
Subjects who discontinue study treatment for reasons other than progressive disease (PD)
will continue to attend PFS Follow-up (FU) Visits every 12 (±1) weeks from the EoT Visit
until the occurrence of PD, loss to follow up, consent withdrawal, death, the start of
subsequent systemic antineoplastic therapy, or study termination, whichever occurs first.
Only patients enrolled in Part 2 will be followed for survival. To assess survival
status, subjects will be contacted (which may be by phone or hospital visit, whichever is
preferable) every 3 months from the first dose of OMTX705.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male and female patient aged 18 years and older.
2. Part 1 and 2, monotherapy and combination: Patients with histologically confirmed
advanced (locoregionally recurrent, not amenable to curative therapy) or metastatic
solid tumors that have no standard therapeutic option with a proven clinical
benefit, or are intolerant to these therapies with the following selected tumor
histologies: pancreatic ductal adenocarcinoma (PDAC), gastric cancer (including
gastroesophageal junction tumors), head and neck squamous-cell carcinoma (HNSCC),
esophageal cancer, non-small cell lung cancer (NSCLC), high grade serious ovarian
cancer (HGSOC), breast cancer (BC), colorectal cancer (CRC), and leiomyosarcoma.
3. Subjects with tumors with actionable mutations should have progress to all approved
targeted therapies or have them contraindicated.
4. Measurable disease by RECIST 1.1 on CT, PET/CT or MRI scan.
5. ECOG performance status 0-1
6. Serum albumin ≥3.0 g/dL
7. Adequate bone marrow, hepatic and renal function:
1. Total bilirubin ≤1.5 times upper limit of normal (ULN).
2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times
ULN, (if liver metastases are present, then ≤5 times ULN is allowed).
3. For Dose escalation Phase: Estimated creatinine clearance (CrCL) using the
Cockcroft-Gault formula ≥60 mL/minute. Patients with calculated CrCL <60 mL/min
can be enrolled if measured CrCL is ≥60 mL/min.
4. In the expansion phase CrCL should be ≥30 mL/min.
5. Hemoglobin ≥9 g/dL (whole or partial blood transfusions not allowed in the 2
previous weeks).
6. Absolute neutrophil count (ANC) ≥1.5 x 109/L (growth factors like G-CSF are not
allowed in the 2 previous weeks).
7. Platelet count ≥75 x 109/L (platelet in the 2 previous weeks transfusions not
allowed)
8. Women of childbearing potential (WOCBP) and men with sexual partners who are WOCBP
must be willing to adhere to contraceptive requirements as detailed in the protocol
from at least 1 month prior to study entry to at least 4 months after the last dose
of study treatment.
9. Suitable venous access for safe drug administration and the study-required drug
concentration and pharmacodynamic sampling.
Exclusion Criteria:
1. Treatment with systemic anticancer treatments, investigational products, or major
surgery within 4 weeks before the first dose of study drug or 5 half-lives,
whichever is shorter. Subjects should have recovered from previous treatment
toxicity to grade 1, baseline (except alopecia and peripheral neuropathy). Patients
with endocrinopathies should have the replacement treatment in stable dosing.
2. History of uncontrolled brain metastasis. For asymptomatic subjects, screening brain
imaging is not required.
3. Subject has received extended field radiotherapy ≤4 weeks before the start of
treatment (≤1 weeks for limited field radiation for palliation), and who has not
recovered to grade 1 or better from related side effects of such therapy (except for
alopecia).
4. Active infection requiring parenteral or oral antibiotics.
5. Evidence of serious uncontrolled medical disorder that, in the opinion of the
investigator or medical monitor, makes it unwise for the subject to participate in
the study or that might jeopardize compliance with the protocol.
6. Drainage of ascitic or pleural fluid 2 or more times in the 4 weeks prior to the
first dose of study drug or permanent drain in place for ascites or pleural effusion
symptom management.
7. Psychiatric illness/social circumstances that would limit compliance with study
requirements and substantially increase the risk of AEs or has compromised ability
to provide written informed consent.
8. Clinical evidence of an active second invasive malignancy with the exception of
stable prostate cancer on watchful waiting, in situ cervical cancer, breast ductal
carcinoma in situ or localized non-melanoma skin cancers.
9. Uncontrolled or significant cardiovascular disease defined as NYHA classification
III or IV.
10. Baseline QTc (using the Fridericia correction calculation) > 470 msec.
11. Combination with pembrolizumab only: history of autoimmune disease requiring
systemic immunosuppressive therapy (daily prednisone equivalent doses >10 mg/day).
12. Combination with pembrolizumab only: Subjects who, according to the currently
approved Keytruda® (pembrolizumab) USPI/SmPC, had, with a previous checkpoint
inhibitor (approved or investigational) treatment, an immune-related adverse event
(irAE) for which permanent discontinuation is mandated (any grade 4 event and grade
3 events of pneumonitis, hepatitis, and nephritis). Also, subjects without formal
contraindication due to previous irAE are not eligible if the AE has not resolved to
grade 1 or better and/or still requires steroids (>10 mg of prednisone equivalent
per day) for ongoing management.
13. Combination with pembrolizumab only: patients with a history of
pneumonitis/interstitial lung disease, patients who received live vaccines within 30
days of enrollment, and patients who discontinued prior immune checkpoint inhibitors
due to Grade 2 myocarditis are excluded from enrollment into
pembrolizumab-containing cohorts.
14. Known hepatitis B virus surface antigen seropositive or detectable hepatitis C
infection viral load.
15. Patients positive for human immunodeficiency virus (HIV) are NOT excluded from this
study, but HIV-positive patients must meet the following criteria:
1. have CD4+ T-cell (CD4+) counts ≥350 cells/µL.
2. have not had an opportunistic infection within the past 12 months. Patients on
prophylactic antimicrobials can be included in the trial.
3. should be on established antiretroviral therapy for at least 4 weeks.
4. have an HIV viral load less than 400 copies/mL prior to enrollment.
5. known history of any other relevant congenital or acquired immunodeficiency
other than HIV infection.
16. Known or suspected allergy to study treatment or related products, and specifically
patients with a prior history of life-threatening reaction to polysorbate 20.
17. Women who are pregnant or breastfeeding or trying to become pregnant.
18. Male patients wishing fathering children, planning for future sperm banking, or
expressing concerns about sterility.
19. Patients requiring the concomitant administration of medications that are strong
inhibitors or inducers of CYP3A4, 2D6, 1A2, 2C9, 2B6, and 2C19. In case they are
taking any of these drugs, they should be stopped at least 14 days prior to first
dose.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Beth Israel Deaconess Medical Center
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Bruno Bockorny, MD
Facility:
Name:
ICO L'Hospitalet
Address:
City:
L'Hospitalet de Llobregat
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Marta Gil Martín, MD
Facility:
Name:
Hospital Universitario de Donostia
Address:
City:
San Sebastián
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Ane Areizaga, MD
Facility:
Name:
Clínica Universitaria de Navarra
Address:
City:
Pamplona
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Mariano Ponz, MD
Facility:
Name:
Hospital Universitari Vall d'Hebron
Address:
City:
Barcelona
Country:
Spain
Status:
Not yet recruiting
Contact:
Last name:
María Vieito, MD
Facility:
Name:
Hospital 12 Octubre
Address:
City:
Madrid
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Luis Paz-Ares, MD
Facility:
Name:
Hospital MD Anderson
Address:
City:
Madrid
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Ricardo Cubedo, MD
Facility:
Name:
Onkologikoa
Address:
City:
San Sebastián
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Ander Urriticoechea, MD
Start date:
October 20, 2022
Completion date:
October 2024
Lead sponsor:
Agency:
Oncomatryx Biopharma S.L.
Agency class:
Industry
Source:
Oncomatryx Biopharma S.L.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05547321
