The study is a Phase 1 Open-label Two-stage, Safety and Tolerability Study with Cancer Type-specific Cohorts, Evaluating Subcutaneous Administration of Andes-1537 for Injection in Patients with Advanced Solid Tumors that are Refractory to Standard Therapy or For Which No Standard Therapy Is Available. Patients with unresectable solid tumors that are refractory or have failed standard therapy and are deemed non-eligible or intolerant to further therapy or for which no standard therapy is available will be included in 5 cancer type-specific parallel cohorts. The following tumor types will be evaluated for potential inclusion in each cancer type-specific cohort: gallbladder \& biliary tract carcinoma; cervical carcinoma; gastric carcinoma; pancreatic carcinoma, and colorectal carcinoma.
After screening, 9 patients in each cancer type-specific cohort (gallbladder \& biliary tract carcinoma; cervical carcinoma; gastric carcinoma; pancreatic carcinoma, and colorectal carcinoma) will enter stage 1. These patients will receive a dose of 400 mg of Andes-1537 five times per week for continuous cycles of 4 weeks that will be repeated until the patients presents drug toxicity requiring treatment discontinuation or disease progression with no noted clinical benefit as assessed by the investigator. The safety and tolerability evaluation will be continuous during the study. The efficacy evaluation will be done by analysis of the clinical objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria after patients complete the first two cycles (8 weeks). Thereafter, clinical ORR will be assessed every 8 weeks. Additionally, tumor-cell activity assessment will be performed in biopsy samples after the patients complete the first 2 cycles (8 weeks). Tumor markers assessment according to the type of tumor will be evaluated every 2 cycles and at the end of study (EOS) visit. Analysis of the tumor metabolic activity through the PET-CT scan and quality of life of patients through questionnaire will be evaluated every 2 cycles. As predefined and according with the decision of the Study Safety and Steering Committee (SSC), in those cohorts where minimal clinical response criteria were met or according to the decision of the SSC based on the risk / benefit analysis, considering toxicity criteria and observed biological responses, 15 additional patients will be recruited (total of 24 patients per cohort) for stage 2 of the study. Patients included in stage 2 will receive the same treatment regimen described for stage 1 and will be followed until the patients present disease progression or drug toxicity requiring treatment discontinuation. Patients included in stage 2 will receive the same follow-up as patients in stage 1.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
67
Andes-1537 administered subcutaneously five days per week.
Fundacion Arturo Lopez Perez
Santiago, Santiago Metropolitan, Chile
Centro de Cancer de Nuestra Senora de la Esperanza, Red de Salud UC CHRISTUS
Santiago, Santiago Metropolitan, Chile
Instituto Nacional del Cáncer (INCANCER)
Santiago, Santiago Metropolitan, Chile
Centro de Investigaciones Clinicas Vina del Mar
Viña del Mar, V Region de Valparaiso, Chile
Incidence of treatment-emergent adverse events (TEAEs) through stages 1 and 2 of the study
Assessment of safety and tolerability through the incidence and severity of TEAEs from change in baseline for reported adverse events, safety labs, vital signs, electrocardiograms, and injection site reactions
Time frame: Screening and during cycle treatment (each cycle 4 weeks) until study completion (approximately 24 weeks or earlier if patient discontinues from study)
Objective response rate (ORR) according to RECIST
Computed tomography (CT) or magnetic resonance imaging (MRI) scan of tumors located in chest, abdomen, and pelvis every 8 weeks for change in tumor size from baseline measurements
Time frame: Assessment performed every 8 weeks following completion of 2 treatment cycles (each cycle 4 weeks) from screening to study completion until confirmed disease progression or Andes-1537 toxicity (approximately 24 weeks or earlier if patient discontinues)
Duration of response and duration of stable disease according to RECIST
CT or MRI of tumor every 8 weeks and compared to previous RECIST assessment
Time frame: Assessment performed every 8 weeks following completion of 2 treatment cycles (each cycle 4 weeks) from screening to study completion until confirmed disease progression or Andes-1537 toxicity (approximately 24 weeks or earlier if patient discontinues)
Progression free survival time according to RECIST
CT or MRI of tumor every 8 weeks and compared to previous RECIST assessment
Time frame: Assessment performed every 8 weeks following completion of 2 treatment cycles (each cycle 4 weeks) from screening to study completion until confirmed disease progression or Andes-1537 toxicity (approximately 24 weeks or earlier if patient discontinues)
Andes-1537 tumor-cell biomarker activity in biopsy tissue
Biopsies will be performed at screening prior to treatment and at the end of the second cycle of treatment in tumor tissue that is accessible by procedures such as colonoscopy, endoscopy, endocervical biopsy, etc. Tumor biopsy samples will be assessed for biomarkers of Andes-1537 activity through histology assays.
Time frame: Screening to end of cycle 2 (each cycle 4 weeks) treatment (approximately 8 weeks)
Plasma concentration of Andes-1537 after subcutaneous administration for pharmacokinetic (PK) parameter area under the plasma concentration versus time (AUC)
Plasma samples will be collected in each treatment cycle for evaluation of AUC
Time frame: Screening and during cycle treatment (each cycle 4 weeks) until study completion (approximately 24 weeks or earlier if patient discontinues from study)
Plasma concentration of Andes-1537 after subcutaneous administration for PK parameter maximum plasma concentration (Cmax)
Plasma samples will be collected in each treatment cycle for evaluation of Cmax
Time frame: Screening and during cycle treatment (each cycle 4 weeks) until study completion (approximately 24 weeks or earlier if patient discontinues from study)
Plasma concentration of Andes-1537 after subcutaneous administration for PK parameter time to maximum concentration (Tmax)
Plasma samples will be collected in each treatment cycle for evaluation of Tmax
Time frame: Screening and during cycle treatment (each cycle 4 weeks) until study completion (approximately 24 weeks or earlier if patient discontinues from study)
Plasma concentration of Andes-1537 after subcutaneous administration for PK parameter half-life (t1/2)
Plasma samples will be collected in each treatment cycle for evaluation of t1/2
Time frame: Screening and during cycle treatment (each cycle 4 weeks) until study completion (approximately 24 weeks or earlier if patient discontinues from study)
Incidence of Andes-1537 anti-drug antibodies (ADAs) in the plasma
Assessment of immunogenicity of Andes-1537 following subcutaneous administration by determining the presence of Andes-1537 ADAs in all patients receiving at least 2 treatment cycles. Blood samples will be collected and stored for future analysis of ADAs prior to the first injection of cycle 1 and then every 8 weeks following completion of a treatment cycle, prior to beginning the next cycle, and end-of-study visit.
Time frame: Screening and during cycle treatment (each cycle 4 weeks) until study completion (approximately 24 weeks or earlier if patient discontinues from study)
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