- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05753722
A First-in-human Study of PRTH-101 Monotherapy +/- Pembrolizumab in Subjects With Advanced Malignancies
An Open-Label Phase 1 Dose-Escalation and Expansion Study Investigating the Safety, Pharmacokinetics, Pharmacodynamics, and Activity of PRTH-101 Alone or in Combination With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors
Study Overview
Status
Conditions
Intervention / Treatment
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
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Jeff Janotka
- Phone Number: 617.206.6581
- Email: jeff.janotka@parthenontx.com
Study Contact Backup
- Name: Joseph Paul Eder, MD
- Phone Number: 857.777.6372
- Email: joseph.eder@parthenontx.com
Study Locations
-
-
Texas
-
San Antonio, Texas, United States, 78229
- Recruiting
- NEXT Oncology
-
Contact:
- Kayla Grossi
- Email: kgrossi@nextoncology.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Subject must be willing and able to read, understand, and sign an Informed Consent Form.
- Subject must be age ≥18 years.
- 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.
- 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.
- Subject must have an Eastern Cooperative Oncology Group performance status (PS) 0-1.
- Subject must have a predicted life expectancy of ≥3 months.
Subject must have the following laboratory values (obtained ≤14 days prior to enrollment):
- Calculated creatinine clearance must be ≥30 mL/min by Cockcroft-Gault formula calculation
- Total bilirubin ≤1.5 × ULN unless has known history of Gilbert's syndrome (in which case, total bilirubin must be ≤3 × ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤1.5 × ULN, or ≤3 x ULN in the presence of liver metastases
- Hemoglobin ≥9.0 g/dL
- Platelets ≥100 × 109 cells/L 9
- Absolute neutrophil count ≥1.5 ×10 cells/L (without the use of hematopoietic growth factors)
- Corrected QT interval (QTc) ≤470 milliseconds (as calculated by the Fridericia correction formula)
- Women of child-bearing potential (WOCBP) must have a negative pregnancy test within 3 days prior to first administration of PRTH-101.
- 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.
- Subject must be willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.
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.
- The subject is not enrolled in any other clinical trial and is not receiving other therapy directed at their malignancy.
- The subject is willing to undergo pre-and post-treatment skin biopsies.
Exclusion Criteria:
- 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.
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.
- Alopecia, and vitiligo
- Grade ≤2 neuropathy
- Well-controlled hypo/hyperthyroidism or other endocrinopathies that are well controlled with hormone replacement
- Subject has undergone a major surgery (excluding minor procedures e.g., placement of vascular access) <2 months prior to administration of PRTH-101.
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.
- Subject has undergone or is anticipated to undergo organ transplantation including allogeneic or autologous stem-cell transplantation, at any time.
- Subject has a diagnosis of immunodeficiency, either primary or acquired.
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.
- Subject has an active or prior history of autoimmune disease requiring immunosuppressive therapy. Exceptions can be made in discussion with the medical monitor.
- 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.
- 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.
- Subject has leptomeningeal carcinomatosis, regardless of treatment history.
- 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.
- Subject has active and clinically significant bacterial, fungal, or viral infection, including known Hepatitis A, B, or C or HIV (testing not required).
- 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).
- Women who are pregnant or breastfeeding.
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.
- Subject has any contraindications to the imaging assessments or other study procedures that subjects will be undergoing.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: PRTH-101
Mono-therapy
|
PRTH-101 is a humanized immunoglobulin gamma-1 (IgG1) monoclonal antibody
|
Experimental: PRTH-101 with Pembrolizumab
Combo therapy
|
PRTH-101 is a humanized immunoglobulin gamma-1 (IgG1) monoclonal antibody
PRTH-101 in combination with Pembrolizumab
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evaluate the Adverse Events (AEs), including Serious Adverse Events (SAEs), that occur in patients treated with PRTH-101
Time Frame: Up to 4 years
|
To evaluate the safety of PRTH-101 as assessed by Adverse Events (AEs), including Serious Adverse Events (SAEs) and Dose Limiting Toxicities (DLTs)
|
Up to 4 years
|
Maximum Tolerated Dose
Time Frame: Up to 4 years
|
Maximum dose level not requiring dose de-escalation under Bayesian design rules
|
Up to 4 years
|
Pharmacokinetic (PK) profile of PRTH-101 alone and in combination with pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1a and Phase 1b as well as Phase 1c will include the accumulation ratio.
|
Up to 4 years
|
Pharmacokinetic (PK) profile of PRTH-101 alone and in combination with pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1a and Phase 1b as well as Phase 1c will include PK maximum concentration (Cmax)
|
Up to 4 years
|
Pharmacokinetic (PK) profile of PRTH-101 alone and in combination with pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1a and Phase 1b as well as Phase 1c will include observed serum concentration (Tmax)
|
Up to 4 years
|
Pharmacokinetic (PK) profile of PRTH-101 alone and in combination with pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1a and Phase 1b as well as Phase 1c will include last measurable concentration (Clast),
|
Up to 4 years
|
Pharmacokinetic (PK) profile of PRTH-101 alone and in combination with pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1a and Phase 1b as well as Phase 1c will include time of last measurable concentration (Tlast,)
|
Up to 4 years
|
Pharmacokinetic (PK) profile of PRTH-101 alone and in combination with pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1a and Phase 1b as well as Phase 1c will include area under curve up to the last measurable concentration (AUClast)
|
Up to 4 years
|
Pharmacokinetic (PK) profile of PRTH-101 alone and in combination with pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1a and Phase 1b as well as Phase 1c will include,volume of distribution (Vd,)
|
Up to 4 years
|
Pharmacokinetic (PK) profile of PRTH-101 alone and in combination with pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1a and Phase 1b as well as Phase 1c will include drug clearance (CL,)
|
Up to 4 years
|
Pharmacokinetic (PK) profile of PRTH-101 alone and in combination with pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1a and Phase 1b as well as Phase 1c will include the time required for plasma concentration of a drug to decrease by 50% (t1⁄2.)
|
Up to 4 years
|
Anti-tumor activity of PRTH-101 alone and in combination with pembrolizumab
Time Frame: Up to 4 years
|
Best overall response as assessed by RECIST v1.1
|
Up to 4 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To evaluate the incidence and persistence of anti-PRTH-101 antibody formation and its impact on the PK profile of PRTH-101
Time Frame: Up to 4 years
|
Evaluate anti-drug antibody in serum over multiple timepoints and its impact on the PK profile of PRTH-101
|
Up to 4 years
|
To evaluate the incidence and persistence of anti- PRTH-101 antibody formation and its impact on the PK profile of PRTH-101 in combination with pembrolizumab antibody therapy
Time Frame: Up to 4 years
|
Evaluate anti-drug antibody in serum over multiple timepoints and its impact on the PK profile of PRTH-101 in combination with pembrolizumab antibody therapy
|
Up to 4 years
|
To evaluate the PK of pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1b as well as Phase 1c will include the accumulation ratio
|
Up to 4 years
|
To evaluate the PK of pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1b as well as Phase 1c will include PK maximum concentration (Cmax)
|
Up to 4 years
|
To evaluate the PK of pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1b as well as Phase 1c will include observed serum concentration (Tmax)
|
Up to 4 years
|
To evaluate the PK of pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1b as well as Phase 1c will include last measurable concentration (Clast)
|
Up to 4 years
|
To evaluate the PK of pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1b as well as Phase 1c will include time of last measurable concentration (Tlast)
|
Up to 4 years
|
To evaluate the PK of pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1b as well as Phase 1c will include area under curve up to the last measurable concentration (AUClast)
|
Up to 4 years
|
To evaluate the PK of pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1b as well as Phase 1c will include volume of distribution (Vd)
|
Up to 4 years
|
To evaluate the PK of pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1b as well as Phase 1c will include drug clearance (CL)
|
Up to 4 years
|
To evaluate the PK of pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1b as well as Phase 1c will include the time required for plasma concentration of a drug to decrease by 50% (t1⁄2.)
|
Up to 4 years
|
To define the PK profile of PRTH-101 together with pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1b as well as Phase 1c will include accumulation ratio
|
Up to 4 years
|
To define the PK profile of PRTH-101 together with pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1b as well as Phase 1c will include PK maximum concentration (Cmax)
|
Up to 4 years
|
To define the PK profile of PRTH-101 together with pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1b as well as Phase 1c will include observed serum concentration (Tmax)
|
Up to 4 years
|
To define the PK profile of PRTH-101 together with pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1b as well as Phase 1c will include last measurable concentration (Clast)
|
Up to 4 years
|
To define the PK profile of PRTH-101 together with pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1b as well as Phase 1c will include time of last measurable concentration (Tlast)
|
Up to 4 years
|
To define the PK profile of PRTH-101 together with pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1b as well as Phase 1c will include area under curve up to the last measurable concentration (AUClast)
|
Up to 4 years
|
To define the PK profile of PRTH-101 together with pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1b as well as Phase 1c will include volume of distribution (Vd)
|
Up to 4 years
|
To define the PK profile of PRTH-101 together with pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1b as well as Phase 1c will include drug clearance (CL)
|
Up to 4 years
|
To define the PK profile of PRTH-101 together with pembrolizumab
Time Frame: Up to 4 years
|
PK parameters for Phase 1b as well as Phase 1c will include the time required for plasma concentration of a drug to decrease by 50% (t1⁄2.)
|
Up to 4 years
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PRTH-101-0001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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