RECRUITING

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

Conditions

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

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.

Official Title

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

Quick Facts

Study Start:2023-03-03

Study Completion:2027-09-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05753722

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. 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.	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. 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. 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: 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.

Inclusion Criteria

Exclusion 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.
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.

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.
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.
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:
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.

Contacts and Locations

Study Contact

Jeff Janotka

CONTACT

617.206.6581

jeff.janotka@incendiatx.com

Joseph Paul Eder, MD

CONTACT

857.777.6372

joseph.eder@incendiatx.com

Principal Investigator

Joseph Paul Eder, MD

STUDY_CHAIR

Incendia Therapeutics

Study Locations (Sites)

Yale Cancer Center

New Haven, Connecticut, 06511

United States

Mass General Cancer Center

Boston, Massachusetts, 02114

United States

Providence Cancer Institute Franz Clinic

Portland, Oregon, 97213

United States

University of Pittsburgh Medical Center Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232

United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 27232

United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

United States

Next Oncology

Irving, Texas, 75039

United States

NEXT Oncology

San Antonio, Texas, 78229

United States

Next Oncology

Fairfax, Virginia, 22031

United States

Collaborators and Investigators

Sponsor: Incendia Therapeutics

Joseph Paul Eder, MD, STUDY_CHAIR, Incendia Therapeutics

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-03-03

Study Completion Date2027-09-30

Study Record Updates

Study Start Date2023-03-03

Study Completion Date2027-09-30

Terms related to this study

Additional Relevant MeSH Terms

Advanced or Metastatic Solid Tumors