Clinical Trials /

PTX-35 in Patients With Advanced Solid Tumors

NCT04430348

Description:

A Phase I, First-in-Human, Dose-Escalation Study to Evaluate the Safety of the Monoclonal Antibody PTX-35 in Patients with Advanced Solid Tumors Refractory to Standard of Care

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: PTX-35 in Patients With Advanced Solid Tumors
  • Official Title: PTX35-001 A Phase I, First-in-Human, Dose-Escalation Study to Evaluate the Safety of the Monoclonal Antibody PTX-35 in Patients With Advanced Solid Tumors Refractory to Standard of Care

Clinical Trial IDs

  • ORG STUDY ID: PTX35-001
  • NCT ID: NCT04430348

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
PTX-35PTX-35 Dose Level 1

Purpose

A Phase I, First-in-Human, Dose-Escalation Study to Evaluate the Safety of the Monoclonal Antibody PTX-35 in Patients with Advanced Solid Tumors Refractory to Standard of Care

Detailed Description

      This is an open-label, single arm, first-in-human, Phase I study of intravenous
      administration of PTX-35 to patients with advanced solid tumors refractory to, or ineligible
      for, or who refuse available SOC. Five escalating dose levels of PTX-35 will be explored
      using a traditional 3+3 design based on dose-limiting toxicities (DLTs) until optimal
      immunological dose (OID) or maximum tolerated dose (MTD) is established.
    

Trial Arms

NameTypeDescriptionInterventions
PTX-35 Dose Level 1ExperimentalDose Level 1: PTX-35 0.01 mg/kg
  • PTX-35
PTX-35 Dose Level 2ExperimentalDose Level 2: PTX-35 0.03 mg/kg
  • PTX-35
PTX-35 Dose Level 3ExperimentalDose Level 3: PTX-35 0.10 mg/kg
  • PTX-35
PTX-35 Dose Level 4ExperimentalDose Level 4: PTX-35 0.30 mg/kg
  • PTX-35
PTX-35 Dose Level 5ExperimentalDose Level 5: PTX-35 1.0 mg/kg
  • PTX-35

Eligibility Criteria

        Inclusion Criteria:

        In order to participate in this study, a patient must:

          1. Be willing and have the capacity to sign the written informed consent form.

          2. Be male or female of at least 18 years of age at the time of signing informed consent.

          3. Have a documented diagnosis of metastatic or advanced, unresectable solid tumor
             disease. Patient must have progressed or recurred following standard of care (SOC)
             therapies, or are ineligible for, or who refuse other safe and effective SOC
             therapies, and whom the Investigator believes may benefit from experimental treatment
             with PTX-35.

          4. Have an acceptable organ function, as defined below:

               1. Albumin ≥ 2.5 g/dL

               2. Total bilirubin < 3.0 × upper limit of normal (ULN), unless patient has Gilbert's
                  syndrome

               3. Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 3.0 × ULN, or

                    -  5 × ULN in the case of liver metastases

               4. Calculated or measured creatinine clearance > 35 mL/minute per the
                  Cockcroft-Gault formula

               5. Absolute neutrophil count ≥ 1,500/mm3

               6. Hemoglobin ≥ 9 g/dL

               7. Platelet count ≥ 100,000/mm3

          5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

          6. Have life expectancy of at least three months.

          7. Patients, both females and males, of childbearing/reproductive potential must agree to
             use adequate contraception while included in the trial and for six months after the
             last treatment with PTX-35.

        Exclusion Criteria:

        In order to participate in this study, a patient must not:

          1. Have received any systemic anticancer therapy including small molecules, chemotherapy,
             radiation therapy, monoclonal antibodies or any other experimental drug within 4 weeks
             of first dose of PTX-35. Adjuvant anti hormonal treatment(s) for prior breast cancer
             or prostate cancer are allowed. (Note: washout for palliative radiation therapy is 2
             weeks).

          2. Have clinically significant cardiac disease, including:

               1. Onset of unstable angina within 6 months of signing the Informed Consent Form
                  (ICF).

               2. Acute myocardial infarction within 6 months of the signing the ICF.

               3. Known congestive heart failure (Grade III or IV as classified by the New York
                  Heart Association); and/ or a known decreased cardiac ejection fraction (LVEF) of
                  < 45%.

               4. Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or
                  diastolic blood pressure ≥ 100 mmHg, despite optimal medical management.

          3. Have known or clinically suspected leptomeningeal disease. Stable, previously treated
             metastases in the brain or spinal cord, are allowed as long as these are considered
             stable (by CT or MRI), and not requiring systemic corticosteroids.

          4. Have a history of ≥ Grade 3 allergic reactions, or suspected allergy or intolerance to
             monoclonal antibody therapies.

          5. Have a history of suspected cytokine release syndrome (CRS).

          6. Have any known immunodeficiency disorders (testing not required).

          7. Have received prior allogeneic stem cell transplant.

          8. Have ongoing or current autoimmune disease. Permanent but stable and manageable immune
             related adverse events (irAE) from prior therapies are permissible, if prednisone
             equivalent corticosteroid use does not exceed 10 mg/day.

          9. Have any other condition requiring concurrent systemic immunosuppressive therapy
             (other than allowable exceptions which do not exceed 10mg/day of
             prednisone/corticosteroid use).

         10. Have clinically significant active viral, bacterial or fungal infection requiring:

               1. Intravenous treatment with antimicrobial therapy completed less than two weeks
                  prior to first dose, or

               2. Oral treatment with antimicrobial therapy completed less than one week prior to
                  first dose. Prophylactic treatment with antibiotics (e.g. for dental extractions)
                  is allowed.

         11. Have had major surgery (requiring general anesthesia or inpatient hospitalization)
             within four weeks before first administration of PTX-35.

         12. Have had a known tetanus/diphtheria vaccine within the past 10 years.

         13. Have known additional malignancy that is active and/or progressive requiring
             treatment; exceptions include basal cell or squamous cell skin cancer, in situ
             cervical cancer, or other cancer for which the patient has been disease-free for at
             least two years.

         14. Have known previously untreated or symptomatic metastases in the brain or spinal cord
             requiring steroids. Patients with treated and stable CNS metastases may be enrolled
             after approval of the sponsor and/or Medical Monitor.

         15. Have any other ongoing significant, uncontrolled medical condition in the opinion of
             the Investigator.

         16. Have known positive serology for human immunodeficiency virus (HIV), hepatitis B, or
             hepatitis C (except in cases of immunity after cured infection). Testing not required.

         17. Have a history of substance abuse, medical, psychological or social conditions that
             may interfere with the patient's participation in the trial or evaluation of the trial
             result.

         18. Be a female patient who is pregnant or breast feeding.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of dose-limiting toxicities (DLTs) per NCI CTCAE v5.0 during the trial
Time Frame:Up to 12 months
Safety Issue:
Description:Number of dose-limiting toxicities (DLTs) per NCI CTCAE v5.0 during the trial

Secondary Outcome Measures

Measure:Determine the optimal immunological dose (OID) of PTX-35.
Time Frame:Up to 12 months
Safety Issue:
Description:Optimal Immunological Dose (OID; dose where T-reg plateau is observed)
Measure:Determine the maximum tolerated dose (MTD) of PTX-35.
Time Frame:Up to 12 months
Safety Issue:
Description:Maximum tolerated dose (MTD; highest dose level at which ≤ 1 patient of at least 6 patients experienced a DLT during the first two treatment cycles).
Measure:Determine PK maximum concentration (Cmax)
Time Frame:Up to 12 months
Safety Issue:
Description:Determine PK maximum concentration (Cmax)
Measure:Determine PK area under curve up to the last measurable concentration (AUClast)
Time Frame:Up to 12 months
Safety Issue:
Description:Determine PK area under curve up to the last measurable concentration (AUClast)
Measure:Determine PK trough observed serum concentration (Ctrough)
Time Frame:Up to 12 months
Safety Issue:
Description:Determine PK trough observed serum concentration (Ctrough)
Measure:Determine PK terminal elimination half-life (T1/2λz)
Time Frame:Up to 12 months
Safety Issue:
Description:Determine PK terminal elimination half-life (T1/2λz)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Heat Biologics

Last Updated

June 10, 2020