PTX-35 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: PTX-35


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In order to participate in this study, a patient must: Be willing and have the capacity to sign the written informed consent form. Be male or female of at least 18 years of age at the time of signing informed consent. 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. Have an acceptable organ function, as defined below: Albumin ≥ 2.5 g/dL Total bilirubin < 3.0 × upper limit of normal (ULN), unless patient has Gilbert's syndrome Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 3.0 × ULN, or 5 × ULN in the case of liver metastases Calculated or measured creatinine clearance > 35 mL/minute per the Cockcroft-Gault formula Absolute neutrophil count ≥ 1,500/mm3 Hemoglobin ≥ 9 g/dL Platelet count ≥ 100,000/mm3 Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Have life expectancy of at least three months. 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: 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). Have clinically significant cardiac disease, including: Onset of unstable angina within 6 months of signing the Informed Consent Form (ICF). Acute myocardial infarction within 6 months of the signing the ICF. 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%. Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥ 100 mmHg, despite optimal medical management. 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. Have a history of ≥ Grade 3 allergic reactions, or suspected allergy or intolerance to monoclonal antibody therapies. Have a history of suspected cytokine release syndrome (CRS). Have any known immunodeficiency disorders (testing not required). Have received prior allogeneic stem cell transplant. 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. Have any other condition requiring concurrent systemic immunosuppressive therapy (other than allowable exceptions which do not exceed 10mg/day of prednisone/corticosteroid use). Have clinically significant active viral, bacterial or fungal infection requiring: Intravenous treatment with antimicrobial therapy completed less than two weeks prior to first dose, or 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. Have had major surgery (requiring general anesthesia or inpatient hospitalization) within four weeks before first administration of PTX-35. Have had a known tetanus/diphtheria vaccine within the past 10 years. 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. 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. Have any other ongoing significant, uncontrolled medical condition in the opinion of the Investigator. 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. 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. Be a female patient who is pregnant or breast feeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PTX-35 Dose Level 1<br>Dose Level 1: PTX-35 0.01 mg/kg | Drug: PTX-35<br>* Monoclonal antibody PTX-35<br>|
| Experimental: PTX-35 Dose Level 2<br>Dose Level 2: PTX-35 0.03 mg/kg | Drug: PTX-35<br>* Monoclonal antibody PTX-35<br>|
| Experimental: PTX-35 Dose Level 3<br>Dose Level 3: PTX-35 0.10 mg/kg | Drug: PTX-35<br>* Monoclonal antibody PTX-35<br>|
| Experimental: PTX-35 Dose Level 4<br>Dose Level 4: PTX-35 0.30 mg/kg | Drug: PTX-35<br>* Monoclonal antibody PTX-35<br>|
| Experimental: PTX-35 Dose Level 5<br>Dose Level 5: PTX-35 1.0 mg/kg | Drug: PTX-35<br>* Monoclonal antibody PTX-35<br>|
| Experimental: PTX-35 Dose Level 6<br>Dose Level 6: PTX-35 3.0 mg/kg | Drug: PTX-35<br>* Monoclonal antibody PTX-35<br>|
| Experimental: PTX-35 Dose Level 7<br>Dose Level 7: PTX-35 10.0 mg/kg | Drug: PTX-35<br>* Monoclonal antibody PTX-35<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of dose-limiting toxicities (DLTs) per NCI CTCAE v5.0 during the trial | Number of dose-limiting toxicities (DLTs) per NCI CTCAE v5.0 during the trial | Up to 12 months | 
| Frequency of treatment-emergent adverse events (TEAEs) related to PTX-35 during the trial | Frequency of treatment-emergent adverse events (TEAEs) related to PTX-35 during the trial | Up to 12 months | 
| Frequency of serious adverse events (SAEs) related to PTX-35 during the trial | Frequency of serious adverse events (SAEs) related to PTX-35 during the trial | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the optimal immunological dose (OID) of PTX-35. | Optimal Immunological Dose (OID; dose where T-reg plateau is observed) | Up to 12 months | 
| Determine the maximum tolerated dose (MTD) of PTX-35. | 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). | Up to 12 months | 
| Determine PK maximum concentration (Cmax) | Determine PK maximum concentration (Cmax) | Up to 12 months | 
| Determine PK area under curve up to the last measurable concentration (AUClast) | Determine PK area under curve up to the last measurable concentration (AUClast) | Up to 12 months | 
| Determine PK trough observed serum concentration (Ctrough) | Determine PK trough observed serum concentration (Ctrough) | Up to 12 months | 
| Determine PK terminal elimination half-life (T1/2λz) | Determine PK terminal elimination half-life (T1/2λz) | Up to 12 months |