A Phase I/IIa Study to Evaluate the Safety, Pharmacokinetics and Efficacy of PTT-936, an Alpha Kinase 1 (ALPK1) Activator, Alone or in Combination With Anti-PD-1/L1 in Patients With Locally Advanced or Metastatic Solid Tumors

Study Identifier:
PTT-936-101
CT.gov Identifier:
NCT06244992
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
N/A
Study Contact Information:
(210) 593-5651 or [email protected]
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Study Summary

This Phase 1/2a study will explore the safety and efficacy of PTT-936, an Alpha Kinase 1 (ALPK1) activator, used alone or in combination with anti-PD-1/L1 therapy in patients with locally advanced or metastatic solid tumors. The study is divided into two parts: Phase 1 (Part A) focuses on determining the pharmaceutically active dosage range and evaluating the safety profile of PTT-936 when administered as a monotherapy. Phase 2a (Part B) will assess the safety and efficacy of PTT-936 combined with anti-PD-1/L1 therapy in patients suitable for anti- PD-1/L1 monotherapy. The study aims to understand how PTT-936, alone or in combination, impacts tumor progression and patients9; overall response.

To evaluate the safety and tolerability of PTT-936 monotherapy in patients with advanced unresectable or metastatic solid tumors who have progressed on SOC or who do not have SOC within the pharmacologically active dose (PAD) range, which may include determining the MTD

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Solid Tumor
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I/II
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: PTT-936 Dose Level 1
    • Read More
  • Drug: Experimental: PTT-936 Dose Level 2
  • Drug: Experimental: PTT-936 Dose Level 3
  • Drug: Experimental: PTT-936 Dose Level 4
  • Drug: Experimental: PTT-936 Dose Level 5
  • Drug: Experimental: PTT-936 and anti-PD-1/L1 combination therapy
  • Drug: Experimental Drugs
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    Inclusion criteria
    • 1. Voluntarily signed informed consent form (ICF).
    • 2. Ability and willingness to adhere to all study procedures.
    • 3. Male or female patients ≥ 18 years of age at the time of signing the ICF.
    • 4. Locally advanced unresectable or metastatic solid tumor confirmed by histology or
    • cytology
    • 5. For Part A: On tumor imaging, as assessed by RECIST v1.1 and iRECIST, with measurable
    • or unmeasurable disease. For Part B: On tumor imaging, as assessed by RECIST v1.1 and
    • iRECIST, with at least one measurable disease.
    • 6. Life expectancy ≥ 3 months.
    • 7. Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0-1 for Part A and
    • Part B.
    • 8. Adequate end-organ and hematopoietic function, defined based on the following
    • laboratory results obtained within 7 days prior to the first dose of study treatment
    • [Day 1]):
    • 1. Absolute neutrophil count (ANC) ≥ 1.5×109/L (1500/μL), without granulocyte
    • colony-stimulating factor (G-CSF) support. Note that G-CSF may be administered
    • until 14 days prior to Cycle 1 Day 1 (C1D1).
    • 2. Platelet count ≥ 90×109/L (90,000/μL) without transfusion within 14 days prior to
    • C1D1.
    • 3. Hemoglobin ≥ 90 g/L (9 g/dL). Note that patients may be transfused or receive
    • erythropoietic treatment to meet this criterion until 14 days prior to C1D1.
    • 4. Creatinine clearance ≥ 60 mL/min.
    • 5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x the
    • upper limit of normal (ULN) with or without primary or metastatic liver tumor
    • lesions.
    • 6. Total bilirubin (TBIL) ≤ 1.5 x ULN.
    • 7. For patients not receiving therapeutic anticoagulation: International Normalized
    • Ratio (INR), activated partial thromboplastin time (aPTT) and prothrombin time
    • (PT) ≤ 1.5 x ULN.
    • 8. For patients receiving warfarin: INR ≤ 3.0 x ULN and no bleeding within 14 days
    • prior to Day 1. Patients receiving therapeutic anticoagulation must be on a
    • stable dose for a minimum of 14 days prior to Day 1. Patients on low molecular
    • weight heparin will be allowed.
    • 1 Voluntary signing of the Informed Consent Form (ICF)
    • 2 Able and willing to comply with all study procedures
    • 3 Male or female patients aged ≥ 18 years at the time of signing the ICF
    • 4 BMI ≥ 18 kg/m2
    • 5 Patients with locally advanced unresectable or metastatic solid tumors confirmed by histology or cytology, and a. For Part A: Prior SOC therapy has failed or is intolerant. ? Please note that prior therapy may include ICIs such as anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4) therapy
    • 6 For Part A: Presence of measurable or non-measurable disease based on tumor imaging as assessed by RECIST v1.1 and iRECIST
    • 7 Expected survival time ≥ 3 months
    • 8 (ECOG) performance status (PS): 0-1
    • 9 Have adequate end-organ and hematopoietic function
    • 10 For women of childbearing potential (WOCBP, Appendix 6): must agree to maintain complete abstinence or use at least 1 acceptable method of contraception from screening to 3 months after the last dose of study drug. Acceptable methods of contraception are those that have a low failure rate (i.e., <1% per year) when used alone or in combination with consistent and correct use, such as intrauterine devices, hormonal contraception, barrier methods (e.g., condoms plus spermicidal foam/gel/film/suppositories). Female subjects must refrain from donating eggs
    • 11 For sexually active men (whose female partners are of childbearing potential): Must agree to maintain complete abstinence or use barrier contraception (e.g., condoms plus spermicidal foam/gel/film/suppository) from screening to 3 months after the last dose of study drug. Male subjects must not donate sperm during this period. This criterion can be waived for male patients who have undergone vasectomy > 6 months before the first dose
    Exclusion criteria
    • 1. Patients with leptomeningeal (LMD) metastases or patients with new and/or progressive
    • brain metastases at the time of study entry. Patients with treated brain metastases
    • are eligible if there is no evidence of progression for at least 4 weeks after central
    • nervous system (CNS)-directed treatment (radiotherapy and/or surgery), as ascertained
    • by clinical examination and brain imaging (MRI or CT) during the screening period.
    • 2. History of primary malignancy other than the diseases under study, not in remission
    • greater than three (3) years prior to Day 1. Exceptions that do not require a 3-year
    • remission include: adequately treated non-melanoma skin cancer, cervical carcinoma in
    • situ on biopsy or squamous intraepithelial lesion on Papanicolaou (PAP) smear, in situ
    • prostate cancer (with no evidence of active disease for two [2] years prior to Day 1),
    • or resected melanoma in situ and radically resected papillary thyroid carcinoma.
    • 3. Persistence of Adverse Events (AEs) from prior anti-cancer therapy that have not
    • resolved to Grade 1 (except for alopecia and hypothyroidism), or any history of Grade
    • ≥ 3 immune-related adverse events (irAEs), Grade ≥ 2 pneumonitis, hypophysitis or
    • encephalitis related to immunotherapy, or other Grade ≥ 3 drug-related CNS toxicity.
    • 4. Active systemic autoimmune disease or a history of autoimmune disorder that may
    • relapse (e.g., systemic lupus erythematosus [SLE], rheumatoid arthritis, inflammatory
    • bowel disease [IBD], autoimmune thyroid disorder*, multiple sclerosis, vasculitis,
    • glomerulitis, eczema, psoriasis, etc.).
    • *Note that primary or secondary hypothyroidism, well controlled with hormone
    • replacement therapy is permitted.
    • 5. Major trauma or major surgery within 4 weeks prior to Day 1 or anticipated major
    • surgery during study participation.
    • 6. Serious unhealing wound, ulcer, or bone fracture.
    • 7. History of and/or presence of any of the following cardiovascular and cerebrovascular
    • events or conditions:
    • 1. History of myocardial infarction, unstable or severe angina, or arterial
    • thrombotic event (such as cerebrovascular attack [CVA] or transient ischemic
    • attack [TIA]) within 12 months prior to Day 1.
    • 2. Significant abnormalities on the screening of ECG, including corrected QT
    • interval (QTc interval) > 470 msec (average of triplicate measurements,
    • corrected for heart rate using Fridericia's formula), second degree (Mobitz type
    • II) or third degree atrioventricular (AV) block, or other clinically significant
    • (in the Investigator's opinion) arrhythmia.
    • 3. Current New York Heart Association (NYHA) stage II-IV congestive heart failure
    • (CHF).
    • 4. Left ventricular ejection fraction (LVEF) < 50%.
    • • Note that LVEF assessment by echocardiogram (ECHO) scan performed as part of
    • the patient's regular care within 4 weeks prior to the screening visit may be
    • used for confirmation of eligibility.
    • 5. Other clinically significant (in the Investigator's opinion) cardiac diseases
    • (e.g., valvular disease, cardiomegaly, ventricular hypertrophy, cardiomyopathy,
    • myocarditis, etc.).
    • 6. Uncontrolled hypertension (defined as a systolic blood pressure [SBP] ≥ 150 mmHg
    • and/or diastolic blood pressure (DBP) ≥ 100 mmHg at screening), despite
    • appropriate antihypertensive therapy, or poor compliance with an antihypertensive
    • regimen.
    • 8. Active or recent (past 6 months) bleeding disorder, including gastrointestinal (GI)
    • bleeding, as evidenced by hematemesis, significant hemoptysis, or melena within 6
    • months prior to Day 1.
    • 9. Uncontrolled diabetes.
    • 10. Chronic severe liver disease or Child-Pugh B or C liver cirrhosis.
    • 11. History of alcoholism or drug abuse within the past year.
    • 1 Patients with leptomeningeal (LMD) metastases or new and/or progressive brain metastases at study entry were included.
    • 2 Prior to the first dose of the study, there was a history of other primary malignancies other than the disease being studied that had not been in remission for more than 3 years.
    • 3 AEs caused by previous anticancer treatment persist and have not subsided to grade 1 (except alopecia and hypothyroidism), or any history of grade ≥3 immune-related adverse events (irAEs), grade ≥2 non-infectious pneumonia, hypophysitis or encephalitis related to immunotherapy, or other grade ≥3 drug-related CNS toxicity
    • 4 Active systemic autoimmune disease or history of autoimmune disease with the potential for recurrence
    • 5 Major trauma or major surgery within 4 weeks before the first dose, or major surgery expected during the study
    • 6 Have severe, unhealed wounds, ulcers, or broken bones
    • 7 Previous and/or current presence of any of the following cardiovascular and cerebrovascular events or diseases: a. Myocardial infarction, unstable or severe angina, or arterial thrombotic events (e.g., cerebrovascular attack [CVA] or transient ischemic attack [TIA]) within 12 months prior to first dose. b. Significant abnormalities on ECG at screening, including QTc interval >470 msec (average of three measurements, corrected for heart rate using Fridericia's formula), second-degree (Mobitz type II) or third-degree atrioventricular (AV) block, or other clinically significant arrhythmias (in the opinion of the investigator). c. Current New York Heart Association (NYHA) class II-IV congestive heart failure (CHF). d. Left ventricular ejection fraction (LVEF) <50%. ? Please note that LVEF assessment by echocardiogram (ECHO) scan may be used to confirm eligibility as part of the patient's routine medical care within 4 weeks prior to the screening visit. e. Other (in the opinion of the investigator) clinically significant heart diseases (e.g., valvular disease, cardiomegaly, ventricular hypertrophy, cardiomyopathy, myocarditis, etc.) f. Hypertension that is poorly controlled despite appropriate antihypertensive treatment (defined as systolic blood pressure [SBP] ≥ 150 mmHg and/or diastolic blood pressure (DBP) ≥ 100 mmHg at screening), or poor compliance with antihypertensive treatment regimen
    • 8 Currently have an active lung infection that requires treatment
    • 9 The following tests are positive at screening: a. Human immunodeficiency virus (HIV). b. Hepatitis B surface antigen (HBsAg). For patients with primary hepatocellular carcinoma, HBsAg positivity is allowed, but the patient must be taking anti-hepatitis B medication and HBV-DNA is below the detection limit. c. Hepatitis B core antibody (HBcAb), unless the subsequent hepatitis B virus (HBV) DNA test result is below the detection limit. d. Hepatitis C virus (HCV) antibody test, unless the subsequent HCV ribonucleic acid (RNA) test shows that the HCV viral load is <15 IU/mL
    • 10 Known allergy to study drug or any component of study drug

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START San Antonio
    San Antonio, TX, United States, 78229
    Investigator
    Amita Patnaik
    Status
    Recruiting
    Condition(s) Treated at Site
    Solid Tumor