Trial Title:
A First-in-human Study of PRTH-101 Monotherapy +/- Pembrolizumab in Subjects With Advanced Malignancies
NCT ID:
NCT05753722
Condition:
Advanced or Metastatic Solid Tumors
Conditions: Official terms:
Pembrolizumab
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:
Biological
Intervention name:
PRTH-101
Description:
PRTH-101 is a humanized immunoglobulin gamma-1 (IgG1) monoclonal antibody
Arm group label:
PRTH-101
Arm group label:
PRTH-101 with Pembrolizumab
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
PRTH-101 in combination with Pembrolizumab
Arm group label:
PRTH-101 with Pembrolizumab
Summary:
The goal of this Open-Label Study is to evaluate the safety and tolerability of PRTH-101
alone or in combination with pembrolizumab in adults with advance or metastatic solid
tumors.
Detailed description:
The goal of this Open-Label Study is to evaluate the safety and tolerability of PRTH-101
alone or in combination with pembrolizumab in adults with advance or metastatic solid
tumors.
PRTH-101 is a therapeutic antibody that specifically binds to and blocks DDR1, a protein
expressed on tumor cells that binds collagen to make a minimally permeable physical
barrier that blocks immune cells from interacting with and attacking tumor cells. These
"immune cell-excluded" solid tumors are resistant to attack by the immune system (as well
as other existing therapies). By disabling DDR1, the collagen fibers lose alignment and
loosen, creating gaps in the tumor barrier, thus allowing T-cells to enter and naturally
attack the tumor.
The main question[s] it aims to answer are:
- to evaluate the safety and tolerability of PRTH-101 as mono therapy and in
combination with pembrolizumab,
- to determine the recommended Phase 2 dose as mono therapy and in combination with
pembrolizumab,
- to evaluate anti-tumor activity of PRTH-101 as mono therapy and in combination with
pembrolizumab in selected indications
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Subject must be willing and able to read, understand, and sign an Informed Consent
Form.
2. Subject must be age ≥18 years.
3. Subject has metastatic or advanced, unresectable malignancy and measurable disease
per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed at
Screening, excluding hepatocellular carcinoma, sarcomas, and gliomas.
4. Subject has a pathologically documented advanced/unresectable or metastatic cancer
that is refractory to or intolerable to or the subject is unwilling or ineligible to
receive standard treatment known to confer benefit or for which no standard
treatment is available.
5. Subject must have an Eastern Cooperative Oncology Group performance status (PS) 0-1.
6. Subject must have a predicted life expectancy of ≥3 months.
7. Subject must have the following laboratory values (obtained ≤14 days prior to
enrollment):
1. Calculated creatinine clearance must be ≥30 mL/min by Cockcroft-Gault formula
calculation
2. Total bilirubin ≤1.5 × ULN unless has known history of Gilbert's syndrome (in
which case, total bilirubin must be ≤3 × ULN)
3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤1.5 × ULN,
or ≤3 x ULN in the presence of liver metastases
4. Hemoglobin ≥9.0 g/dL
5. Platelets ≥100 × 109 cells/L 9
6. Absolute neutrophil count ≥1.5 ×10 cells/L (without the use of hematopoietic
growth factors)
7. Corrected QT interval (QTc) ≤470 milliseconds (as calculated by the Fridericia
correction formula)
8. Women of child-bearing potential (WOCBP) must have a negative pregnancy test within
3 days prior to first administration of PRTH-101.
9. WOCBP and males with female partners of child-bearing potential must agree to use
adequate birth control throughout their participation and for 90 days following the
last dose of PRTH-101.
10. Subject must be willing to adhere to the study visit schedule and the prohibitions
and restrictions specified in this protocol.
11. Subject must have a site of disease amenable to biopsy and be a candidate for tumor
biopsy according to the treating institution's guidelines or have archived tissue
available (Section 12.3) at enrollment.
a. Subjects with sites of disease not amenable to biopsy may be considered after
discussion with the Sponsor.
12. The subject is not enrolled in any other clinical trial and is not receiving other
therapy directed at their malignancy.
13. The subject is willing to undergo pre-and post-treatment skin biopsies.
Exclusion Criteria:
1. Subject has received prior treatment with systemic agents, including, but not
limited to, radio-immunoconjugates, antibody-drug conjugates, immune/cytokines, and
monoclonal antibodies (e.g., checkpoint inhibitors) within 28 days or five
half-lives of the drug, whichever is shorter.
2. Subject has ongoing toxicity from prior therapy >Grade 1 according to the CTCAE,
with the following exceptions. Such exceptions must be assessed by the Investigator
(and approved by the Sponsor) as not placing the subject at undue safety risk from
participating in this study.
1. Alopecia, and vitiligo
2. Grade ≤2 neuropathy
3. Well-controlled hypo/hyperthyroidism or other endocrinopathies that are well
controlled with hormone replacement
3. Subject has undergone a major surgery (excluding minor procedures e.g., placement of
vascular access) <2 months prior to administration of PRTH-101.
4. Subject has received radiation therapy <28 days prior to administration of PRTH-101.
a. Exception: limited (e.g., pain palliation) radiation therapy is allowed prior to
and during study treatment as long as there are no acute toxicities, and the subject
has measurable disease outside the radiation field.
5. Subject has undergone or is anticipated to undergo organ transplantation including
allogeneic or autologous stem-cell transplantation, at any time.
6. Subject has a diagnosis of immunodeficiency, either primary or acquired.
7. Subject has received treatment with systemic steroids or any other form of
immunosuppressive therapy within 14 days prior to administration of PRTH-101.
a. Exception: inhaled or topical (to include mouthwash) steroids and adrenal
replacement doses are permitted in the absence of active autoimmune disease.
8. Subject has an active or prior history of autoimmune disease requiring
immunosuppressive therapy. Exceptions can be made in discussion with the medical
monitor.
9. Subject has a known severe intolerance to or hypersensitivity reactions to
monoclonal antibodies, Fc-bearing proteins (e.g., soluble receptors or other Fc
fusion proteins), or IV immunoglobulin preparations; prior history of human
antihuman antibody response; known allergy to any of the study medications, their
analogues, or excipients in the various formulations of any agent.
10. Subject has Central Nervous System (CNS) tumor involvement not definitively treated
with surgery or radiation that is active (including evidence of cerebral edema by
MRI, or progression from prior imaging study, or has had any requirement for
steroids, or clinical symptoms of/from CNS metastases within 28 days prior to study
treatment.
11. Subject has leptomeningeal carcinomatosis, regardless of treatment history.
12. Subject has current second malignancy at other sites (exceptions: nonmelanomatous
skin cancer, adequately treated in situ carcinoma [e.g., cervical], or indolent
prostate cancer under observation). A history of other malignancies is allowed as
long as subject has been free of recurrence for ≥2 years, or if the subject has been
treated with curative intent within the past 2 years and, in the opinion of the
Investigator, is unlikely to have a recurrence.
13. Subject has active and clinically significant bacterial, fungal, or viral infection,
including known Hepatitis A, B, or C or HIV (testing not required).
14. Subject has received live vaccines within the past 30 days (inactivated vaccines are
allowed; seasonal vaccines should be up to date >30 days prior to administration of
PRTH-101).
15. Women who are pregnant or breastfeeding.
16. History of any of the following ≤6 months before first dose:
a. Congestive heart failure New York Heart Association Grade III or IV b. Unstable
angina c. Myocardial infarction d. Unstable symptomatic ischemic heart disease e.
Uncontrolled hypertension despite appropriate medical therapy f. Ongoing symptomatic
cardiac arrhythmias of > Grade 2 g. Symptomatic cerebrovascular events, or any other
serious cardiac condition (e.g., pericardial effusion or restrictive
cardiomyopathy); chronic atrial fibrillation on stable anticoagulant therapy is
allowed.
17. Subject has any contraindications to the imaging assessments or other study
procedures that subjects will be undergoing.
18. Subject has any medical or social condition that, in the opinion of the
Investigator, might place a subject at increased risk, affect compliance, or
confound safety or other clinical study data interpretation.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Yale Cancer Center
Address:
City:
New Haven
Zip:
06511
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ingrid Palma
Investigator:
Last name:
Patricia LoRusso, DO
Email:
Principal Investigator
Facility:
Name:
Mass General Cancer Center
Address:
City:
Boston
Zip:
02114
Country:
United States
Status:
Recruiting
Contact:
Last name:
Alicia Piotrowski
Investigator:
Last name:
Aparna Parikh, MD
Email:
Principal Investigator
Facility:
Name:
Providence Cancer Institute Franz Clinic
Address:
City:
Portland
Zip:
97213
Country:
United States
Status:
Recruiting
Contact:
Last name:
Patrick Rethwisch
Investigator:
Last name:
Rachel Sanborn, MD
Email:
Principal Investigator
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
Investigator:
Last name:
Priyanka Chablani, MD
Email:
Principal Investigator
Facility:
Name:
Vanderbilt-Ingram Cancer Center
Address:
City:
Nashville
Zip:
27232
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rebekah Caza
Investigator:
Last name:
Jordan Berlin, MD
Email:
Principal Investigator
Facility:
Name:
The University of Texas MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Anjali Raina
Investigator:
Last name:
Funda Meric-Bernstam, MD
Email:
Principal Investigator
Facility:
Name:
Next Oncology
Address:
City:
Irving
Zip:
75039
Country:
United States
Status:
Recruiting
Contact:
Last name:
Selena Morales
Investigator:
Last name:
Shiraj Sen, MD, PhD
Email:
Principal Investigator
Facility:
Name:
NEXT Oncology
Address:
City:
San Antonio
Zip:
78229
Country:
United States
Status:
Recruiting
Contact:
Last name:
Brianna Flores
Investigator:
Last name:
David Sommerhalder, MD
Email:
Principal Investigator
Facility:
Name:
Next Oncology
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Status:
Recruiting
Contact:
Last name:
Blake Patterson
Investigator:
Last name:
Alex Spira, MD,PhD,FACP
Email:
Principal Investigator
Start date:
March 3, 2023
Completion date:
September 30, 2027
Lead sponsor:
Agency:
Incendia Therapeutics
Agency class:
Industry
Source:
Incendia Therapeutics
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05753722
