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Active Not RecruitingNCT03816358

Testing the Combination of Anetumab Ravtansine With Either Nivolumab, Nivolumab and Ipilimumab, or Gemcitabine and Nivolumab in Advanced Pancreatic Cancer

A Phase I Study of Anetumab Ravtansine in Combination With Either Anti-PD-1 Antibody, or Anti-CTLA4 and Anti-PD-1 Antibodies or Anti-PD-1 Antibody and Gemcitabine in Mesothelin-Positive Advanced Pancreatic Adenocarcinoma

Status
Active Not Recruiting
Phase
Phase 1
Study type
Interventional
Enrollment
74 (estimated)
Sponsor
National Cancer Institute (NCI) · NIH
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

Summary

This phase I trial studies the side effects and best dose of anetumab ravtansine when given together with nivolumab, ipilimumab and gemcitabine hydrochloride in treating patients with mesothelin positive pancreatic cancer that has spread to other places in the body (advanced). Anetumab ravtansine is a monoclonal antibody, called anetumab ravtansine, linked to a chemotherapy drug called DM4. Anetumab attaches to mesothelin positive cancer cells in a targeted way and delivers DM4 to kill them. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving anetumab ravtansine together with nivolumab, ipilimumab, and gemcitabine hydrochloride may work better in treating patients with pancreatic cancer.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the safety and tolerability of anetumab ravtansine with the following combinations in patients with mesothelin positive pancreatic adenocarcinoma. SECONDARY OBJECTIVES: I. To assess the preliminary anti-tumor activity of anetumab ravtansine (anetumab) in combination with nivolumab, nivolumab and ipilimumab, nivolumab and gemcitabine hydrochloride (gemcitabine) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 overall response rate (ORR). II. To characterize the pharmacokinetics (PK) profile of anetumab (apparent diffusion coefficient \[ADC\]), total antibody (ADC and cleaved free antibody), DM4 and DM4-Me (S-Methyl metabolite of DM4). III. To evaluate the tumor microenvironment and immune changes in tumor and peripheral blood over the course of treatment to identify predictors of response or resistance to treatment. IV. To measure the progressive disease (PD) effects of this combination including molecular and immune biomarkers in tumor biopsies and peripheral blood. EXPLORATORY OBJECTIVES: I. To characterize mesothelin, PD-L1, CD3, CD4, CD8 expressions at baseline and after treatment in mesothelin positive pancreatic cancer patients. II. To evaluate level of soluble mesothelin and megakaryocyte potentiation factor (MPF) over the course of treatment and to correlate these biomarkers with clinical outcome. III. To perform whole exome sequencing (WES) +/- ribonucleic acid sequencing (RNAseq) in the tumor biopsy specimens and correlation genomic (e.g. mutational burden) and transcriptomic biomarkers with clinical outcome. IV. To evaluate mononuclear phagocyte system (MPS) function, Fc-gamma receptors (FcgammaRs) and hormone and chemokine mediators as methods to evaluate factors affecting the PK and PD of these agents. V. To evaluate anti-drug antibody (ADA) titres changes pre and post treatment and correlate them with PK, toxicity and responses. OUTLINE: This is a dose-escalation study of anetumab ravtansine. Patients are assigned to 1 of 3 arms. ARM I: Patients receive anetumab ravtansine intravenously (IV) over 1 hour on day 1 and nivolumab IV over 30 minutes on day 8 of cycle 1 and on day 1 of subsequent cycles. Treatment repeats every 21 or 28 days (cycle 1) for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a biopsy and collection of blood on study. ARM II: Patients receive anetumab ravtansine IV over 1 hour on day 1 and nivolumab IV over 30 minutes on day 8 of cycle 1 and on day 1 of subsequent cycles. Patients also receive ipilimumab IV over 30 minutes on day 8 of cycle 1 and on day 1 of cycles 2-4. Treatment repeats every 21 or 28 days (cycle 1) for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a biopsy and collection of blood on study. ARM III: Patients receive anetumab ravtansine IV over 1 hour on day 1 and nivolumab IV over 30 minutes on day 8 of cycle 1 and on day 1 of subsequent cycles. Patients also receive gemcitabine hydrochloride over 30-40 minutes on days 1 and 8. Treatment repeats every 21 or 28 days (cycle 1) for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a biopsy and collection of blood on study. After completion of study treatment, patients are followed up every 8 weeks for up to 100 days, then every 12 weeks thereafter.

Conditions

Interventions

TypeNameDescription
BIOLOGICALAnetumab RavtansineGiven IV
PROCEDUREBiopsy ProcedureUndergo biopsy
PROCEDUREBiospecimen CollectionUndergo collection of blood
DRUGGemcitabine HydrochlorideGiven IV
BIOLOGICALIpilimumabGiven IV
BIOLOGICALNivolumabGiven IV

Timeline

Start date
2019-12-09
Primary completion
2027-01-31
Completion
2027-01-31
First posted
2019-01-25
Last updated
2026-04-13

Locations

45 sites across 2 countries: United States, Canada

Regulatory

Source: ClinicalTrials.gov record NCT03816358. Inclusion in this directory is not an endorsement.