A First-in-human Study of PRTH-101 Monotherapy +/- Pembrolizumab in Subjects With Advanced Malignancies

NCT05753722 | Recruiting Phase 1 FDA Drug

• 1 other identifier: PRTH-101-0001
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

Advanced or Metastatic Solid Tumors; Non Small Cell Lung Cancer; NSCLC

Keywords

Non Small Cell Lung Cancer; NSCLC

Outcome Measures

Primary Outcomes (12)

• Evaluate the Adverse Events (AEs), including Serious Adverse Events (SAEs), that occur in patients treated with PRTH-101

  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

  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

  PK parameters for Phase 1a and Phase 1b will include the accumulation ratio.

  Up to 4 years

• Pharmacokinetic (PK) profile of PRTH-101 alone and in combination with pembrolizumab

  PK parameters for Phase 1a and Phase 1b will include PK maximum concentration (Cmax)

  Up to 4 years

• Pharmacokinetic (PK) profile of PRTH-101 alone and in combination with pembrolizumab

  PK parameters for Phase 1a and Phase 1b will include observed serum concentration (Tmax)

  Up to 4 years

• Pharmacokinetic (PK) profile of PRTH-101 alone and in combination with pembrolizumab

  PK parameters for Phase 1a and Phase 1b will include last measurable concentration (Clast),

  Up to 4 years

• Pharmacokinetic (PK) profile of PRTH-101 alone and in combination with pembrolizumab

  PK parameters for Phase 1a and Phase 1b will include time of last measurable concentration (Tlast,)

  Up to 4 years

• Pharmacokinetic (PK) profile of PRTH-101 alone and in combination with pembrolizumab

  PK parameters for Phase 1a and Phase 1b 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

  PK parameters for Phase 1a and Phase 1b will include, volume of distribution (Vd,)

  Up to 4 years

• Pharmacokinetic (PK) profile of PRTH-101 alone and in combination with pembrolizumab

  PK parameters for Phase 1a and Phase 1b will include drug clearance (CL,)

  Up to 4 years

• Pharmacokinetic (PK) profile of PRTH-101 alone and in combination with pembrolizumab

  PK parameters for Phase 1a and Phase 1b 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

  Best overall response as assessed by iRECIST in 1c

  Up to 4 years

Secondary Outcomes (20)

• To evaluate the incidence and persistence of anti-PRTH-101 antibody formation 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

  Up to 4 years

• To evaluate the PK of pembrolizumab

  Up to 4 years

• To evaluate the PK of pembrolizumab

  Up to 4 years

• To evaluate the PK of pembrolizumab

  Up to 4 years

Study Arms (2)

PRTH-101

EXPERIMENTAL

Mono-therapy

Biological: PRTH-101

PRTH-101 with Pembrolizumab

EXPERIMENTAL

Combo therapy

Biological: PRTH-101; Biological: Pembrolizumab

Interventions

PRTH-101 BIOLOGICAL

PRTH-101 is a humanized immunoglobulin gamma-1 (IgG1) monoclonal antibody

PRTH-101; PRTH-101 with Pembrolizumab

Pembrolizumab BIOLOGICAL

PRTH-101 in combination with Pembrolizumab

PRTH-101 with Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incendia Therapeutics: lead

Study Sites (11)

Honor Health Research Institute

Scottsdale, Arizona, 85258, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06511, United States

RECRUITING

Mass General Cancer Center

Boston, Massachusetts, 02114, United States

RECRUITING

Providence Cancer Institute Franz Clinic

Portland, Oregon, 97213, United States

RECRUITING

University of Pittsburgh Medical Center Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

COMPLETED

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 27232, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

NEXT Houston

Houston, Texas, 77054, United States

RECRUITING

Next Oncology

Irving, Texas, 75039, United States

RECRUITING

NEXT Oncology

San Antonio, Texas, 78229, United States

RECRUITING

Next Oncology

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Joseph Paul Eder, MD

  Incendia Therapeutics

  STUDY CHAIR

Central Study Contacts

James Corkery

CONTACT

508-851-7690; james.corkery@incendiatx.com

Joseph Paul Eder, MD

CONTACT

857.777.6372; joseph.eder@incendiatx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2023
• First Posted: March 3, 2023
• Study Start: March 3, 2023
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: February 23, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)