About this trial
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 patients' overall response.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Voluntarily signed informed consent form (ICF).
Ability and willingness to adhere to all study procedures.
Male or female patients ≥ 18 years of age at the time of signing the ICF.
Locally advanced unresectable or metastatic solid tumor confirmed by histology or cytology
Disqualifiers
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.
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.
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.
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.).
Trial design
Sequential
Treatments tested in this trial
PTT-936
DrugEligible patients will receive single-agent PTT-936 administered per orally (PO).
Combination of PTT-936 and anti-PD-1/L1 therapy
DrugEligible patients will receive combination treatment consisting of PTT-936 administered PO in combination with a Standard of Care (SOC) regimen of an anti-PD-1/L1 agent administered intravenously (IV).
Treatment groups
6
Treatment groupsSee each treatment group below.
Trial outcomes
Primary outcomes
Incidence of TEAEs and TRAEs (with severity determined using NCI CTCAE v5.0), Grade >3 TEAEs, Grade >3 TRAEs, SAEs, and AESIs
Overall Response Rate (ORR): defined as the percentage of patients who achieved Complete Response (CR) or Partial Response (PR) according to RECIST v1.1 and iRECIST during the study
Sponsors and contacts
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