Trial Title:
Safety & PK of MBRC-101 in Advanced Refractory Solid Tumors
NCT ID:
NCT06014658
Condition:
Cancer
Conditions: Official terms:
Antibodies
Immunoconjugates
Study type:
Interventional
Study phase:
Phase 1
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:
Antibody-Drug Conjugate
Description:
MBRC-101: AN ANTI-EPHA5 MONOMETHYL AURISTATIN E (MMAE) ANTIBODY DRUG CONJUGATE
Arm group label:
Phase 1 Dose Escalation
Arm group label:
Phase 1b Expansion
Summary:
This is a first-in-human (FIH), open label Phase 1/1b study in patients with advanced
metastatic solid tumors refractory to standard treatment. Phase 1 will identify potential
optimal biologically relevant doses (OBRD) and the maximum tolerated dose (MTD) of
MBRC-101 at one 1 or more dosing regimens. Phase 1b will evaluate the safety and
preliminary clinical activity of MBRC-101 at potential OBRDs. Phase 1 and Phase 1b will
both characterize single and multiple-dose PK profiles and evaluate incidence and
persistence of anti-MBRC-101 Ab.
Detailed description:
Phase 1, dose escalation, will enroll approximately 30 patients with advanced or
metastatic solid tumors refractory to standard therapy. EphA5 expression will not be
required for enrollment into Phase 1 but will be assessed retrospectively.
Phase1b, the dose expansion phase will evaluate the safety and preliminary clinical
activity of MBRC-101 at potential OBRDs and dosing regimens in patients with advanced or
metastatic solid tumors refractory to standard therapy. Phase 1b will enroll 3 expansion
cohorts of ≈ 20 patients per cohort (n ≈ 60 total).
Safety will be monitored by the Safety Review Committee (SRC) at each dose escalation in
Phase 1 and at regular intervals throughout Phase 1b.
Overall Response Rate (ORR), Progression Free Survival (PFS), Response Rate (RR), Overall
Survival (OS), Disease Control Rate (DCR), and Complete and Partial response (CR and PR)
will be used to evaluate efficacy per RECIST v1.1 criteria based on the results of
positron emission tomography and computed tomography (PET-CT), computerized tomography
(CT), and magnetic resonance imaging (MRI) scans.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Provide written consent on an Informed Consent Form (ICF), approved by an
Institutional Review Board (IRB)/Independent Ethics Committee (IEC), prior to any
study-specific evaluation. Patients should have the ability to read and understand
the ICF, ask for any clarifications from the study staff, and be able to comply with
all planned study procedures.
2. 18 years of age or older at the time of informed consent.
3. Female patients must be at least 2 years postmenopausal (defined as 2 years without
menses), surgically sterile (at least 6 months prior to dosing; must be documented)
or practicing effective contraception (must agree to use 2 forms of contraception, 1
of which must be a barrier method) and willing to continue to use effective
contraception for the duration of study participation and for 6 months after the
final dose of study drug. Female patients must be nonlactating and have a negative
serum pregnancy test result at screening and baseline.
4. Male patients must agree to use effective contraception (must agree to use 2 forms
of contraception, 1 of which must be a barrier method) for the duration of study
participation and for 6 months after the final dose of study drug.
5. Have a histologic or cytologic diagnosis of malignant solid tumor for which there
are no standard of care treatment options known to confer a clinical benefit or for
which the patient is ineligible or declines.
A. For Phase 1 dose escalation: histologic or cytologic diagnosis of malignant solid
tumor of any type. The Sponsor may remove specific tumor indications based on
emerging, real-time study data.
B. For Phase 1b dose expansion:
i. Cohort A: Histologic or cytologic diagnosis of NSLC (adenocarcinoma and SCC).
ii. Cohort B: Histologic or cytologic diagnosis of TNBC or HR positive, HER2
negative breast cancer.
iii. Cohort C: Histologic or cytologic diagnosis of the following advanced
metastatic solid tumors refractory to standard treatment: pancreatic adenocarcinoma,
gastric adenocarcinoma, hepatocellular carcinoma, ovarian adenocarcinoma, and
squamous cell carcinoma including, but not limited to, primary malignancies of the
head and neck, esophagus, cervix, and skin. The Sponsor may add or remove specific
tumor indications based on emerging, real-time study results.
6. For Phase 1 and Phase 1b, availability of a tumor tissue sample (formalin-fixed
paraffin embedded [FFPE]) must be confirmed for analysis of EphA5 expression based
on IHC. Tumor biopsies are not required and should not be performed to assess
eligibility.
A. For Dose Escalation (Phase 1) and Dose Expansion (Phase 1b), tumor EphA5
expression will not be required for enrollment.
7. For Dose Escalation (Phase 1), patients may have evaluable disease or measurable
disease according to RECIST v1.1). For Dose Expansion (Phase 1b), patients must have
measurable disease according to RECIST v1.1.
8. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
9. Life expectancy ≥ 3 months as assessed by the investigator.
10. Hematologic function, as follows (no red blood cell [RBC] or platelet transfusions
are allowed within 14 days of the first dose of MBRC-101):
A. Absolute neutrophil count (ANC) ≥ 1.0 × 109/L B. Platelet count ≥ 100 × 109/L C.
Hemoglobin ≥ 9 g/dL
11. eGFR ≥ 30 mL/min by the CKD-EPI or similar equation or as measured by 24 hour urine
collection.
12. Total bilirubin ≤ 1.5 × upper limit normal (ULN).
13. AST ≤ 3.0 × ULN.
14. ALT ≤ 3.0 × ULN.
15. International normalised ratio (INR) < 1.5 (or ≤ 3.0 if on therapeutic
anticoagulation).
16. Treatment with other agents for cancer, if received, must have been discontinued ≥ 2
weeks prior to first dose of study drug.
Prior ADC therapy is allowed. Prior agents conjugated to MMAE are allowed for Phase 1 but
not Phase 1b.
Exclusion Criteria:
1. Preexisting sensory neuropathy Grade ≥ 2.
2. Preexisting motor neuropathy Grade ≥ 2.
3. Uncontrolled central nervous system metastases
4. Use of any investigational drug within 14 days prior to the first dose of study
drug.
5. Any anticancer therapy within 14 days prior to the first dose of study drug,
including: small molecules, immunotherapy, chemotherapy, monoclonal antibody
therapy, radiotherapy, or any other agents to treat cancer (anti-hormonal therapy
given for advanced prostate cancer or as adjuvant therapy for early stage, hormone
receptor (HR) positive breast cancer is not considered cancer therapy for the
purpose of this protocol).
6. Patients with immunotherapy related AEs requiring high doses of steroids (≥ 40
mg/day of prednisone) are not eligible.
7. Strong CYP3A or inducers within 14 days prior to the first dose of study drug.
8. Thromboembolic events and/or bleeding disorders ≤ 14 days (e.g., venous
thromboembolism [VTE] or pulmonary embolism [or PE]) prior to the first dose of
study drug.
9. Documented history of a cerebral vascular event (stroke or transient ischemic
attack), unstable angina, myocardial infarction, or cardiac symptoms (including
congestive heart failure) consistent with New York Heart Association Class 3-4
within 6 months prior to the first dose of MBRC-101.
10. A baseline QT (time from the beginning of the Q wave to the end of the T wave)
interval as corrected by Fridericia's formula (QTcF) > 470 msec.
11. Human immunodeficiency virus (HIV) infection with 1 or more of the following:
A. Acquired immunodeficiency syndrome (AIDs)-defining opportunistic infection within
6 months of the start of screening; B. A change in antiretroviral therapy within 3
months of the start of screening and viral load > 500 copies/mL; C. Receiving
antiretroviral therapy that may interfere with study drug; D. CD4 count < 350 at
screening.
12. Active or symptomatic viral hepatitis. Patients who have been properly treated for
hepatitis C infection can be included if they do not have active hepatitis C.
13. Known sensitivity to any of the ingredients of the investigational product MBRC-101.
14. Major surgery within 28 days prior to first dose of study drug.
15. History of another malignancy within 3 years before the first dose of study drug, or
any evidence of residual disease from a previously diagnosed malignancy. Allowed
exceptions are patients with:
A. Non-melanoma skin cancer considered completely cured; B. Localized prostate
cancer treated with curative intent with no evidence of progression; C. Low-risk or
very low-risk (per standard clinical guidelines) localized prostate cancer under
active surveillance without immediate intent to treat; D. Malignancy that is
otherwise considered cured with minimal risk of recurrence.
16. Currently receiving systemic antimicrobial treatment for active infection
(bacterial, viral, or fungal) at the time of first dose of MBRC-101. Routine
antimicrobial prophylaxis is permitted.
17. For Phase 1b dose expansion, prior ADC therapy is not allowed if the agent is
conjugated to MMAE. Prior agents conjugated to MMAE are allowed for Phase 1.
18. Condition or situation which, in the investigator's opinion, may put the patient at
significant risk, may confound the study results, or may interfere significantly
with patient's participation in the study.
19. Any medical, psychiatric, addictive, or other kind of disorder which compromises the
ability of the patient to give written informed consent and/or to comply with
procedures.
20. Active ocular surface disease at baseline or any components of the ophthalmologic
history which, in the investigator's opinion, may place the patient at significant
risk.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
UCSF Helen Diller Family Comprehensive Cancer Center
Address:
City:
San Francisco
Zip:
94158
Country:
United States
Status:
Recruiting
Contact:
Last name:
Phu Lam
Email:
Phu.Lam@ucsf.edu
Investigator:
Last name:
Pam Munster, MD
Email:
Principal Investigator
Facility:
Name:
Horizon Oncology Research
Address:
City:
Lafayette
Zip:
47905
Country:
United States
Status:
Completed
Facility:
Name:
Rutgers Cancer Institute of New Jersey
Address:
City:
New Brunswick
Zip:
08903
Country:
United States
Status:
Recruiting
Contact:
Last name:
Sanjay Goel, MD
Investigator:
Last name:
Sanjay Goel, MD
Email:
Principal Investigator
Facility:
Name:
Carolina BioOncology Institute
Address:
City:
Huntersville
Zip:
28078
Country:
United States
Status:
Recruiting
Contact:
Last name:
John D Powderly, MD
Facility:
Name:
PRISMA Health, Institute for Translational Oncology
Address:
City:
Greenville
Zip:
29605
Country:
United States
Status:
Recruiting
Contact:
Last name:
William J Edenfield, MD
Facility:
Name:
NEXT Oncology
Address:
City:
Austin
Zip:
78758
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andrae Vandross, MD
Facility:
Name:
NEXT Oncology
Address:
City:
Irving
Zip:
75039
Country:
United States
Status:
Recruiting
Contact:
Last name:
Shiraj Sen, MD
Facility:
Name:
NEXT Oncology
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Status:
Recruiting
Contact:
Last name:
Adham Salkeni, MD
Start date:
November 7, 2023
Completion date:
November 2025
Lead sponsor:
Agency:
MBrace Therapeutics
Agency class:
Industry
Source:
MBrace Therapeutics
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06014658
