Phase Ib/IIa Study to Evaluate Safety and Efficacy of Treatment With the Hedgehog Inhibitor NLM-001 and Chemotherapy (Gemcitabine and Nab-Paclitaxel) Plus Zalifrelimab as First Line Treatment in Patients With Advanced Pancreatic Cancer
Overview
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- Nelum Corp
- Enrollment
- 28
- Locations
- 6
- Primary Endpoint
- Treatment efficacy according to response
Overview
Brief Summary
In order to improve the survival rates and decrease progression of pancreatic advanced cancer, this study aims to evaluate the first line treatment approved for this disease (gemcitabine plus nab-paclitaxel) in combination with two experimental drugs, an inhibitor of the signaling pathway of Hedgehog and an immunotherapy drug able of blocking the CTLA-4 receptor.
Detailed Description
Pancreatic cancer is one of the leading neoplasms in the world in terms of mortality, with very low survival rates mainly due to its rapid progression and diagnosis in advanced stages, which makes its treatment extremely difficult.
Gemcitabine plus nab-paclitaxel is currently considered the first-line standard treatment for advanced pancreatic cancer due to this superiority against other treatments.
In order to find an alternative to improve survival of advanced pancreatic cancer, this study aims to evaluate the efficacy with first-line treatment in combination of two experimental drugs, a Hedgehog pathway inhibitor (NLM-001) and a CTLA-4 blocker (zalifrelimab) in previously untreated patients with advanced pancreatic cancer.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 90 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Investigators must ensure that patients are able to understand the requirements of the study and provide informed consent
- •Age ≥18 years
- •Histological or cytological diagnosis of pancreatic adenocarcinoma
- •Stage IV disease
- •No prior treatment for advanced disease. Patients who have received chemotherapy for localize disease are eligible if at least six months have elapsed from the last chemotherapy treatment
- •Measurable disease per RECIST 1.1 as determined by the investigator
- •ECOG (Eastern Cooperative Oncology Group) PS 0-1
- •Sufficient hematopoietic, renal and liver function as defined as:
- •Neutrophil count ≥ 1.5 x 10\*9 / L
- •Platelet count ≥ 100 x 10\*9 / L
Exclusion Criteria
- •Active or uncontrolled infection, disease or serious medical condition that may interfere with the patient's eligibility or treatment
- •History of psychiatric condition that would compromise the patient's ability to understand or comply with the requirements of the protocol, or the ability to provide informed consent
- •Concurrent antineoplastic therapy
- •Pregnant or lactating women
- •History of allergic reactions attributed to compounds of similar chemical structure or similar biological study drug composition
- •History of life-threatening serious adverse events to Gemcitabine or Nab-Paclitaxel
- •Prior chemotherapy or chemo-radiation therapy for advanced pancreatic cancer
- •Patients requiring or being treated with potent CYP3A4 inhibitors and inducers
- •Other malignancies treated within the last 5 years, except in situ cervix carcinoma or nonmelanoma skin cancer
- •History of interstitial lung disease
Arms & Interventions
Investigational treatment
Conventional Chemotherapy (Gemcitabine + nab-paclitaxel) plus NLM-001 plus Zalifrelimab
Intervention: Zalifrelimab (Drug)
Investigational treatment
Conventional Chemotherapy (Gemcitabine + nab-paclitaxel) plus NLM-001 plus Zalifrelimab
Intervention: Gemcitabine (Drug)
Investigational treatment
Conventional Chemotherapy (Gemcitabine + nab-paclitaxel) plus NLM-001 plus Zalifrelimab
Intervention: Nab paclitaxel (Drug)
Investigational treatment
Conventional Chemotherapy (Gemcitabine + nab-paclitaxel) plus NLM-001 plus Zalifrelimab
Intervention: NLM-001 (Drug)
Outcomes
Primary Outcomes
Treatment efficacy according to response
Time Frame: 17 months
Objective Response Rate (ORR): Complete Response (CR) + Partial Response (PR) according to RECIST 1.1 criteria
Secondary Outcomes
- Frequency of occurrence of adverse events(8 months)
- CA 19.9(8 months)
- Collagen structure and PFS(1 month)
- Treatment efficacy according to disease control rate(8 months)
- Treatment efficacy according to Overall Survival (OS)(8 months)
- Gli mRNA and SMA + CAF expression and ORR(1 month)
- Gli mRNA and SMA + CAF expression and PFS(1 month)
- Lymphocyte infiltration and PFS(1 month)
- Treatment efficacy according to Duration of Response (DoR)(8 months)
- Collagen structure and ORR(1 month)
- Treatment efficacy according to progression free survival (PFS)(8 months)
- Lymphocyte infiltration and ORR(1 month)