Study to Evaluate the Safety and Efficacy of Treatment With NLM-001 and Standard Chemotherapy Plus Zalifrelimab in Patients With Advanced Pancreatic Cancer

NCT04827953 | Active Not Recruiting Phase 1

• 2 other identifiers: NLM-2020-01 / NUMANTIA2020-004932-52
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 6

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.

Conditions

Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Treatment efficacy according to response

  Objective Response Rate (ORR): Complete Response (CR) + Partial Response (PR) according to RECIST 1.1 criteria

  17 months

Secondary Outcomes (12)

• Frequency of occurrence of adverse events

  8 months

• Treatment efficacy according to disease control rate

  8 months

• Treatment efficacy according to progression free survival (PFS)

  8 months

• Treatment efficacy according to Duration of Response (DoR)

  8 months

• Treatment efficacy according to Overall Survival (OS)

  8 months

Study Arms (1)

Investigational treatment

EXPERIMENTAL

Conventional Chemotherapy (Gemcitabine + nab-paclitaxel) plus NLM-001 plus Zalifrelimab

Drug: Gemcitabine; Drug: Nab paclitaxel; Drug: NLM-001; Drug: Zalifrelimab

Interventions

Gemcitabine DRUG

Gemcitabine 1000 mg/m2 IV on days 1, 8 and 15 (conventional chemotherapy).

Investigational treatment

Nab paclitaxel DRUG

Nab-Paclitaxel 125 mg/m2 IV on days 1, 8 and 15 (conventional chemotherapy).

Investigational treatment

NLM-001 DRUG

NLM-001 will be administered three cycles consecutively followed by two rest cycles.

Investigational treatment

Zalifrelimab DRUG

Zalifrelimab administration each 6 weeks.

Investigational treatment

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Bilirubin ≤ 1.5 x ULN (upper limit of normal)
• AST and / or ALT ≤2.5 x ULN or ≤5 for patients with liver disease
• Serum creatinine ≤ 1.5 x ULN
• Tumor lesion amenable for safe repeated biopsy
• Women of child-bearing age and men who wish to participate in the study must agree to use appropriate contraceptive methods from the signing of informed consent until 3 months after discontinuation of the study drug

You may not qualify if:

• 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
• Subjects with a history or presence of a known clotting disorder or difficulty achieving haemostasis will be excluded
• Primary or secondary immunodeficiency, including immunosuppressive disease or autoimmune disease (including autoimmune endocrinopathies).
• Note: Subjects with diabetes type 1, vitiligo, psoriasis, hypo-, or hyperthyroid disease not requiring immunosuppressive treatment are eligible. Subjects with Type 2 diabetes mellitus are allowed
• Subjects with a known history of human immunodeficiency virus 1 and 2, human T lymphotropic virus 1.
• Administration of anticancer medications or investigational drugs within the following intervals before the first administration of study drug:

Sponsors & Collaborators

• Nelum Corp: lead
• Apices Soluciones S.L.: collaborator
• Agenus Inc.: collaborator

Study Sites (6)

Hospital Clínico Universitario de Santiago

Santiago de Compostela, A Coruña, 15706, Spain

Location

Hospital Universitario Virgen De La Victoria

Málaga, Andalusia, 29010, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Aragon, 50009, Spain

Location

Hospital Universitario Donostia

Donostia / San Sebastian, Basque Country, 20014, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Catalonia, 08035, Spain

Location

Hospital Universitario Marqués del Valdecilla

Santander, 39008, Spain

Location

MeSH Terms

Interventions

Gemcitabine; Taxes

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Economics; Health Care Economics and Organizations

Study Officials

• Teresa Macarulla, MD

  Hospital Vall d'Hebron

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2021
• First Posted: April 1, 2021
• Study Start: September 1, 2021
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2025
• Last Updated: December 30, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (6)