Phase 1
N=12
Mesothelin-Targeted Immunotoxin LMB-100 in Combination With Tofacitinib in Persons With Previously Treated Pancreatic Adenocarcinoma, Cholangiocarcinoma and Other Mesothelin Expressing Solid Tumors
Neoplasms With Mesothelin Expression · Epithelioid Mesothelioma · Cholangiocarcinoma, Extrahepatic · Adenocarcinoma, Pancreatic
Bottom Line
View on ClinicalTrials.gov: NCT04034238 ↗Enrolled (actual)
12
Serious AEs
68.8%
Results posted
Feb 2022
Primary outcome: Primary: Maximum Tolerated Dose (MTD) of LMB-100 With Tofacitinib — 100 mcg/kg given days 4, 6, 8 every cycle
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- LMB-100 (Drug); Tofacitinib (Drug); Mesothelin Expression (Device)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Dec 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose (MTD) of LMB-100 With Tofacitinib |
100 | — |
| PRIMARY Percentage of Participants With Pancreatobiliary Cancer and LMB-100 Plasma Drug Levels Above Threshold 600ng/mL During Cycle 2 Who Received LMB-100 at Maximum Tolerated Dose |
33.3 | — |
| PRIMARY Number of Participants With Serious Adverse Events Possibly, Probably, and/or Definitely Related to LMB-100 Treated in the Dose Escalation Group |
1; 2 | — |
| SECONDARY Percentage of Participants With LMB-100 Plasma Drug Levels Above Threshold 600ng/mL During Cycle 2 in Dose Escalation |
75 | — |
| SECONDARY Maximum Observed (Peak) Plasma Concentration (Cmax) of LMB-100 |
1644.43; 2160.67; 1466.4 | — |
| SECONDARY Percentage of Participants Without Delayed Formation of Neutralizing Anti-LMB-100 Anti-drug Antibodies (ADAs) |
100; 0; 0 | — |
| SECONDARY Area Under the Plasma Concentration vs. Time Curve Extrapolated to Infinity (AUC(INF)) of LMB-100 |
2415.9; 2918.5; 2804.1 | — |
| SECONDARY Plasma Half-Life (T1/2) of LMB-100 |
1.0; 0.8; 1.2 | — |
| SECONDARY Number of Participants With Serious Adverse Events Possibly, Probably, and/or Definitely Related to LMB-100 Who Have Pancreatobiliary Cancer |
4 | — |
Summary
Background:
The protein mesothelin is found on many kinds of tumors. The drug LMB-100 targets cancer cells that make this protein. Researchers want to see if LMB-100 combined with another drug can help people with these tumors.
Objective:
To find a safe dose of LMB-100 plus tofacitinib in people with pancreatic cancer, bile-duct cancer, and other solid tumors that make mesothelin.
Eligibility:
People ages 18 and older with pancreatic cancer, bile-duct cancer, or any other solid tumor with mesothelin that worsened after treatment or they could not receive standard treatment
Design:
Participants will be screened with:
* Medical history
* Tumor tissue sample. If they do not have a sample, they will have a biopsy.
* Physical exam
* Blood and heart tests
* Scans and x-rays: They may have a dye injected for the scans.
Participants will take the drugs in up to three 21-day cycles. They will take tofacitinib by mouth twice a day on days 1-10 of each cycle. They will have LMB-100 injected into the blood on days 4, 6, and 8 of every cycle. Patients that do not have a medi-port may need to have a central vein access line placed.
Participants will take other drugs on the days they receive LMB-100.
Participants will repeat screening tests during the study. They may have a biopsy at the start of the first 2 cycles.
If participants must stop the study, they will have a safety visit 3-6 weeks after their last dose of the study drug. Some participants may then have visits every 6 weeks.
After treatment, participants will be contacted about once a year. They will be asked about their cancer.
Eligibility Criteria
- INCLUSION CRITERIA:
- Patients must have histologically confirmed solid tumor malignancy for which no curative therapy exists.
- Pancreatic adenocarcinoma, extrahepatic cholangiocarcinoma or epithelioid subtype of mesothelioma, as determined by National Cancer Institute (NCI) Laboratory of Pathology, OR for all other tumor types, at least 20% of tumor cells must express mesothelin. Determination can be made using archival tumor tissue or fresh biopsy if archival tumor tissue is not available.
- All patients must have evaluable disease (i.e., measurable per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. or by following carbohydrate antigen 19-9 (CA19-9) tumor marker). Patients in the expansion cohort must have measurable disease, per RECIST 1.1. evaluation of measurable disease.
- Patients must have received at least one prior standard systemic treatment regimen for advanced disease OR be ineligible to receive available standards due to co-morbidities, prior toxicity, lack of standard options for tumor type, or having received all standards available for prior treatment of early-stage disease OR have refused first-line standard systemic treatment but have received prior anti-cancer treatments.
- Patients with deficient Mismatch Repair (dMMR)/high levels of MicroSatellite Instability (MSI-H) disease must have received at least one prior anti-programmed cell death 1 (PD1) therapy, be ineligible to receive this treatment due to concurrent medical conditions or have refused this therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
- Age >=18 years. Because no dosing or adverse event data are currently available on the use of LMB-100 alone or in combination with tofacitinib in persons with = 1.5 x 10^3 cells/micro liters, platelet count of >= 85,000/micro liters, hemoglobin greater than or equal to 9 g/dL
- Serum albumin >= 2.5 mg/dL without intravenous supplementation
- Adequate liver function: Bilirubin = 50 mL/min. Measured clearance will be used if both numbers are available.
- Must have left ventricular ejection fraction >= 50%
- Must have an ambulatory oxygen saturation of > 88% on room air
- The expansion phase patients must meet all eligibility criteria above AND must have diagnosis of pancreatic adenocarcinoma or extrahepatic cholangiocarcinoma with pathology confirmed to be consistent with one of these diagnoses by NCI Laboratory of Pathology.
- The effects of LMB-100 alone or in combination with tofacitinib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry until 3 months the last dose of study therapy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- Ability of participant to understand and the willingness to sign a written informed consent document.
EXCLUSION CRITERIA
- Known or clinically suspected central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases as CNS penetration of LMB-100 is expected to be poor. CNS metastases are permitted if they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days.
- Evidence of significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results, including significant pulmonary disease other than that related to the primary cancer, uncontrolled diabetes mellitus, and/or significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, unstable angina, or clinically significant pericardial effusion).
- Any known diagnoses, metabolic dysfunction, physical examination findi
Data sourced from ClinicalTrials.gov (NCT04034238). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.