Mesothelin-Targeted Immunotoxin LMB-100 in Combination With Tofacitinib in Persons With Previously Treated Pancreatic Adenocarcinoma, Cholangiocarcinoma and Other Mesothelin Expressing Solid Tumors

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Active, not recruiting
CT.gov ID
NCT04034238
Collaborator
(none)
19
1
2
46.1
0.4

Study Details

Study Description

Brief 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.

Detailed Description

Background:
  • Pancreatic cancer is the fourth most common cause of cancer death in the United States, claiming more than 40,000 lives each year.

  • Incidence nearly equals mortality with just 6% of participants living five years beyond their diagnosis. Most patients are diagnosed at an advanced stage, but even patients with early-stage disease have a long-term survival of less than 20%.

  • Cholangiocarcinoma is a rare disease and just 3,000 patients are diagnosed with the extrahepatic form yearly. The median overall survival of patients with advanced disease receiving standard of care treatment is less than 1 year.

  • Expression of mesothelin (MSLN) in pancreatic ductal adenocarcinoma (PDA) has been examined in several published studies and ranges from 86 to 100%. Similar incidence of expression has been observed in extrahepatic cholangiocarcinoma.

  • In addition to pancreatobiliary tumors, many other solid tumor types also express MSLN such as mesothelioma, colorectal, lung adenocarcinomas, epithelial ovarian, gastric and triple negative breast cancers, as well as some tumors of squamous cell origin.

  • LMB-100 and a closely related immunotoxin also targeting MSLN have been studied in previous Phase 1 clinical studies for mesothelioma and pancreatic cancer.

  • Results from these studies showed that almost all patients formed anti-drug-antibodies (ADAs) that neutralized subsequent injection of the product making it ineffective.

  • Tofacitinib is an oral Janus Kinase-1 and -3 (JAK) inhibitor approved by the FDA for the treatment of rheumatoid arthritis and ulcerative colitis.

  • Pre-clinical studies have shown that tofacitinib can prevent the formation of ADAs against an immunotoxin closely related to LMB-100

  • Co-administration of tofacitinib with immunotoxin increased immunotoxin serum half- life in mice and enhanced anti-tumor efficacy

  • This clinical trial will investigate whether co-administration of tofacitinib with LMB- 100 can prevent or delay the formation of ADAs and thus allow patients to receive additional effective cycles of LMB-100.

Objectives:
  • The primary objective of the dose escalation phase of this study is to assess the safety and tolerability of LMB-100 given in combination with tofacitinib to patients with pancreatic adenocarcinoma, extrahepatic cholangiocarcinoma and other mesothelin-positive solid tumors

  • The primary objective of the expansion phase of this study is to determine whether co-administration of tofacitinib delays formation of neutralizing anti-LMB-100 ADAs through cycle 2 of treatment (as measured by LMB-100 serum drug levels) in patients with pancreatobiliary cancers.

Eligibility:
  • Age >= 18 years

  • Histologically confirmed solid tumor malignancy for which no curative therapy exists

  • Participants must have received at least one prior systemic treatment regimen for their disease OR be ineligible to receive available standard treatments for their disease OR refused first-line standard systemic treatments but have been treated with other anti-cancer agents.

Design:
  • This is a Phase I study which will accrue up to 45 subjects total, accounting for screen failure.

  • Participants will be co-treated for 3 cycles with tofacitinib given orally for the first 10 days of each 21-day cycle, and LMB-100 given on days 4, 6 and 8.

  • A 3+3 dose escalation schema will be used. Two dose levels are planned. One minus dose level could be utilized if dose de-escalation is necessary.

  • Following identification of an optimal dose and schedule, an expansion phase of 15 participants will be initiated at the optimal dose for patients with pancreatic adenocarcinoma and extrahepatic cholangiocarcinoma. At least 8 participants in the expansion phase must have pancreatic adenocarcinoma.

  • Participants on the Dose Escalation and Dose Expansion Arms who appear to be obtaining clinical benefit from LMB-100/tofacitinib after 3 cycles of treatment may elect to receive additional cycles of therapy at the discretion of the principal investigator (PI).

Study Design

Study Type:
Interventional
Actual Enrollment :
19 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Study of Mesothelin-Targeted Immunotoxin LMB-100 in Combination With Tofacitinib in Persons With Previously Treated Pancreatic Adenocarcinoma, Cholangiocarcinoma and Other Mesothelin Expressing Solid Tumors
Actual Study Start Date :
Aug 29, 2019
Actual Primary Completion Date :
Dec 1, 2021
Anticipated Study Completion Date :
Jul 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: 1. Dose escalation

LMB-100 at escalating doses plus tofacitinib

Drug: LMB-100
Arms 1 and 2: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study.

Drug: Tofacitinib
Arms 1 and 2: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study.
Other Names:
  • Xeljanz
  • Device: Mesothelin Expression
    Test for mesothelin expression in tumor tissues for study eligibility

    Experimental: 2. Dose expansion

    LMB-100 at optimal dose plus tofacitinib

    Drug: LMB-100
    Arms 1 and 2: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study.

    Drug: Tofacitinib
    Arms 1 and 2: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study.
    Other Names:
  • Xeljanz
  • Outcome Measures

    Primary Outcome Measures

    1. Maximum Tolerated Dose (MTD) of LMB-100 With Tofacitinib [First cycle of treatment (21 days)]

      MTD is defined as the maximum dose at which less than 33% of participants experience a dose-limiting toxicity (defined as any events occurring within the first cycle of treatment (21 days) such as any death not clearly due to the underlying disease or extraneous causes).

    2. 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 [Plasma LMB-100 levels during Cycle 2 treatment (each cycle = 21 days)]

      This measure assessed how many participants have LMB-100 plasma drug levels higher than threshold (600 ng/mL) during Cycle 2 pharmacokinetics (PK) measurements, a sign of effective prevention of anti-LMB-100 antibodies. The validated enzyme-linked immunosorbent assay (ELISA) test was used to measure plasma LMB-100 concentration. Below 600ng/mL is considered a bad outcome and above 600ng/mL is considered a good outcome.

    3. Number of Participants With Serious Adverse Events Possibly, Probably, and/or Definitely Related to LMB-100 Treated in the Dose Escalation Group [Throughout study treatment until 30 days post-completion, approximately 13 weeks]

      Grade 1-5 adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 observed in participants with pancreatic cancer. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe or medically significant. Grade 4 is life-threatening consequences. Grade 5 is death related to adverse events.

    Secondary Outcome Measures

    1. Percentage of Participants With LMB-100 Plasma Drug Levels Above Threshold 600ng/mL During Cycle 2 in Dose Escalation [Plasma LMB-100 levels during Cycle 2 of treatment (each cycle = 21 days)]

      This measure assessed how many participants in the dose escalation have LMB-100 plasma drug levels higher than threshold (600 ng/mL) during Cycle 2 pharmacokinetics (PK) measurements, a sign of effective prevention of anti-LMB-100 antibodies. The validated enzyme-linked immunosorbent assay (ELISA) test was used to measure plasma LMB-100 concentration. Below 600ng/mL is considered a bad outcome and above 600ng/mL is considered a good outcome.

    2. Maximum Observed (Peak) Plasma Concentration (Cmax) of LMB-100 [Pre-administration, end-of-infusion, then 1, 2, 4, 8-10, 12-16 hours post- LMB-100 during cycle 1 (each cycle = 21 days)]

      The maximum observed analyte concentration in plasma was reported.

    3. Percentage of Participants Without Delayed Formation of Neutralizing Anti-LMB-100 Anti-drug Antibodies (ADAs) [Plasma LMB-100 levels during Cycle 3 treatment (each cycle = 21 days)]

      This measure assessed how many participants have no LMB-100 plasma drug levels higher than threshold (600 ng/mL) during Cycle 3 pharmacokinetics (PK) measurements, a sign of effective prevention of anti-LMB-100 antibodies. The validated enzyme-linked immunosorbent assay (ELISA) test was used to measure plasma LMB-100 concentration. Below 600ng/mL is considered a bad outcome and above 600ng/mL is considered a good outcome.

    4. Area Under the Plasma Concentration vs. Time Curve Extrapolated to Infinity (AUC(INF)) of LMB-100 [Pre-administration, end-of-infusion, then 1, 2, 4, 8-10, 12-16 hours post- LMB-100 during cycle 1 (each cycle = 21 days)]

      AUC is a measure of the serum concentration of LMB-100 over time. It is used to characterize drug absorption.

    5. Plasma Half-Life (T1/2) of LMB-100 [Pre-administration, end-of-infusion, then 1, 2, 4, 8-10, 12-16 hours post- LMB-100 during cycle 1 (each cycle = 21 days)]

      Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.

    6. Number of Participants With Serious Adverse Events Possibly, Probably, and/or Definitely Related to LMB-100 Who Have Pancreatobiliary Cancer [Throughout study treatment until 30 days post-completion, approximately 13 weeks.]

      Grade 1-4 adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 observed in participants with pancreatic cancer. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe or medically significant. Grade 4 is life-threatening consequences. Grade 5 is death related to adverse event.

    Other Outcome Measures

    1. Number of Participants With Serious and/or Non-serious Adverse Events Regardless of Attribution Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). [Throughout study treatment until 30 days post-completion, approximately 13 weeks.]

      Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

    2. Number of Participants With a Dose-Limiting Toxicity (DLT) [First cycle (21 days)]

      A dose limiting toxicity is defined as any events occurring within the first cycle of treatment (21 days) such as any death not clearly due to the underlying disease or extraneous causes, transaminitis that meets criteria for Hy's Law: grade ≥2 elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) with simultaneous elevation of total bilirubin to ≥ 2x ULN while alkaline phosphatase remains < 2x upper limit of normal (ULN). Some hematological toxicities, and Grade ≥3 non-hematological toxicities; and any other drug related toxicity considered significant enough to be qualifies as a DLT in the opinion of the principal investigator. Inability to start cycle 2 within 2 weeks after completing cycle 1 due to drug-related adverse events.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    • 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 <18 years of age, children are excluded from this study.

    • Patients must be more than 14 days removed from most recent minor surgical procedure (such as biliary stenting), 28 days from most recent major surgical procedure and 14 days from radiation therapy, systemic treatments (such as chemotherapy), or experimental drug treatment. All acute toxicities from prior treatment must have resolved to grade 1 or less except alopecia, anemia, peripheral neuropathy, or endocrinopathies corrected by replacement therapy.

    • Adequate hematological function: neutrophil count of >= 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 <2.5 x upper limit of normal (ULN) for all, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x ULN except for patients with significant tumor burden in their liver where AST and ALT < 5x ULN is acceptable in the absence of other etiologies for transaminitis

    • Adequate renal function: creatinine clearance [Estimating glomerular filtration rate (EGFR) method or measured] >= 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 finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition (other than mesothelin [+] cancer diagnosis) that would contraindicate the use of an investigational drug, interfere with tumor measurement or lead to a life expectancy of less than 6 months as judged by the investigator.

    • Contraindication to receiving prophylactic doses of low-molecular weight heparin (LMWH) or direct oral anticoagulants (DOAC) such as current active bleeding (except for grade 1 hematuria or epistaxis), recent history of significant bleeding without subsequent effective medical or surgical intervention, known history of gastric varices, uncontrolled malignant hypertension, history of coagulopathy that confers increased risk of bleeding. Patients on concurrent treatment with anti-platelet agents such as aspirin or clopidogrel are eligible if deemed to have acceptable risk of bleeding in consultation with Hematologist. Patients already receiving prophylactic or therapeutic doses of anticoagulant (heparin-based, or DOAC) for at least 4 weeks with no indication of significant bleeding while on therapy are considered NOT to have a contraindication to this therapy.

    • Inability to administer or unwillingness to comply with recommended venous thromboembolism (VTE) prophylaxis for the duration of study treatment.

    • Prior diagnosis of hematologic malignancy

    • Active or uncontrolled infections (including tuberculosis, human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) or reasonable clinical suspicion of an active infection (such as cholangitis) as tofacitinib suppresses lymphocyte signaling and will impair host response to infection

    • Latent tuberculosis (TB) infection as identified by interferon-gamma release assay (IGRA). If IGRA is indeterminate, tuberculin skin test (TST) may be used to determine status.

    • Live attenuated vaccinations within 14 days prior to treatment.

    • Use of a strong inhibitor or inducer of cytochrome P450 3A4 (CYP3A4) within 14 days prior to enrollment or similarly updated source for a list of such agents)

    • Inability to take or digest oral medication.

    • Dementia or altered mental status that would prohibit informed consent.

    • Pregnant women are excluded from this study because the effects of LMB-100 and/or tofacitinib on the developing fetus are unknown and may have the potential to cause teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with LMB-100 and/or tofacitinib, breastfeeding should be discontinued if the mother is treated with either of these agents.

    • Baseline corrected QT interval by Fredericia (QTcF) interval of > 470 ms, participants with baseline resting bradycardia < 45 beats per minute, or baseline resting tachycardia >100 beats per minute.

    • Participants with contra-indication and/or history of severe hypersensitivity reactions to any components related to LMB-100 and tofacitinib.

    • Patients who have previously received LMB-100 (and therefore have high-levels of preexisting anti-drug antibodies (ADAs) to drug)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 National Institutes of Health Clinical Center Bethesda Maryland United States 20892

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Christine C Alewine, M.D., National Cancer Institute (NCI)

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Christine Alewine, M.D., Principla Investigator, National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT04034238
    Other Study ID Numbers:
    • 190128
    • 19-C-0128
    First Posted:
    Jul 26, 2019
    Last Update Posted:
    Feb 8, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    Yes
    Keywords provided by Christine Alewine, M.D., Principla Investigator, National Cancer Institute (NCI)
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 3/19 subjects were enrolled but not treated (2 in Dose Escalation phase, and 1 in Dose Expansion phase). No data were collected for these participants.
    Arm/Group Title Dose Escalation- Dose Level 1 LMB-100 100 mcg/kg Dose Escalation- Dose Level 2 - LMB -100 140 mcg/kg Dose Expansion LMB-100 100 mcg/kg Enrolled But Not Treated
    Arm/Group Description LMB-100 at escalating doses plus tofacitinib LMB-100: Arms 1: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 1: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study. Mesothelin Expression: Test for mesothelin expression in tumor tissues for study eligibility LMB-100 at escalating doses plus tofacitinib LMB-100: Arms 2: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 2: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study. Mesothelin Expression: Test for mesothelin expression in tumor tissues for study eligibility LMB-100 at optimal dose plus tofacitinib LMB-100: Arms 1: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 1: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study. Participants were enrolled but not treated.
    Period Title: Dose Escalation Phase
    STARTED 7 3 0 2
    COMPLETED 6 3 0 0
    NOT COMPLETED 1 0 0 2
    Period Title: Dose Escalation Phase
    STARTED 0 0 6 1
    COMPLETED 0 0 5 0
    NOT COMPLETED 0 0 1 1

    Baseline Characteristics

    Arm/Group Title Dose Escalation Dose Level 1 LMB-100 100 mcg/kg Dose Escalation Dose Level 2 LMB-100 140 mcg/kg Dose Expansion LMB-100, 100 mcg/kg Total
    Arm/Group Description LMB-100 at escalating doses plus tofacitinib LMB-100: Arms 1: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 1: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study. Mesothelin Expression: Test for mesothelin expression in tumor tissues for study eligibility LMB-100 at escalating doses plus tofacitinib LMB-100: Arms 2: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 2: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study. Mesothelin Expression: Test for mesothelin expression in tumor tissues for study eligibility LMB-100 at optimal dose plus tofacitinib LMB-100: Arms 1: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 1: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study. Total of all reporting groups
    Overall Participants 7 3 6 16
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    5
    71.4%
    2
    66.7%
    2
    33.3%
    9
    56.3%
    >=65 years
    2
    28.6%
    1
    33.3%
    4
    66.7%
    7
    43.8%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    61.79
    (15.99)
    54.53
    (16.26)
    70.68
    (11.36)
    63.76
    (14.79)
    Sex: Female, Male (Count of Participants)
    Female
    4
    57.1%
    1
    33.3%
    0
    0%
    5
    31.3%
    Male
    3
    42.9%
    2
    66.7%
    6
    100%
    11
    68.8%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    14.3%
    0
    0%
    0
    0%
    1
    6.3%
    Not Hispanic or Latino
    3
    42.9%
    2
    66.7%
    2
    33.3%
    7
    43.8%
    Unknown or Not Reported
    3
    42.9%
    1
    33.3%
    4
    66.7%
    8
    50%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    1
    16.7%
    1
    6.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    14.3%
    0
    0%
    1
    16.7%
    2
    12.5%
    White
    6
    85.7%
    3
    100%
    4
    66.7%
    13
    81.3%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    7
    100%
    3
    100%
    6
    100%
    16
    100%

    Outcome Measures

    1. Primary Outcome
    Title Maximum Tolerated Dose (MTD) of LMB-100 With Tofacitinib
    Description MTD is defined as the maximum dose at which less than 33% of participants experience a dose-limiting toxicity (defined as any events occurring within the first cycle of treatment (21 days) such as any death not clearly due to the underlying disease or extraneous causes).
    Time Frame First cycle of treatment (21 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title All Participants in Dose Escalation Dose Level 1, and Dose Level 2
    Arm/Group Description All Participants in Dose Escalation Dose Level 1, and Dose Level 2 administered LMB-100: Both Arms intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 and Tofacitinib orally twice daily on days 1-10 of each cycle, and LMB-100.
    Measure Participants 10
    Number [mcg/kg given days 4, 6, 8 every cycle]
    100
    2. Primary Outcome
    Title 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
    Description This measure assessed how many participants have LMB-100 plasma drug levels higher than threshold (600 ng/mL) during Cycle 2 pharmacokinetics (PK) measurements, a sign of effective prevention of anti-LMB-100 antibodies. The validated enzyme-linked immunosorbent assay (ELISA) test was used to measure plasma LMB-100 concentration. Below 600ng/mL is considered a bad outcome and above 600ng/mL is considered a good outcome.
    Time Frame Plasma LMB-100 levels during Cycle 2 treatment (each cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    Per protocol, this measure includes all participants who meet eligibility criteria for the dose expansion (pancreatobiliary diagnosis) and received LMB-100 at the Maximum Tolerated Dose (Dose Escalation-Dose Level 1 (DL1) and Dose expansion, n =11). Only participants who have pharmacokinetics results during Cycle 2 are evaluable. Five more participants were not evaluable due to not receiving Cycle 2 treatment or not having pharmacokinetics results.
    Arm/Group Title Dose Expansion LMB-100, 100 mcg/kg
    Arm/Group Description LMB-100 at optimal dose plus tofacitinib - 100 mcg/kg LMB-100: Arms 1: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 1: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study.
    Measure Participants 6
    Number [Percentage of participants]
    33.3
    475.7%
    3. Primary Outcome
    Title Number of Participants With Serious Adverse Events Possibly, Probably, and/or Definitely Related to LMB-100 Treated in the Dose Escalation Group
    Description Grade 1-5 adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 observed in participants with pancreatic cancer. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe or medically significant. Grade 4 is life-threatening consequences. Grade 5 is death related to adverse events.
    Time Frame Throughout study treatment until 30 days post-completion, approximately 13 weeks

    Outcome Measure Data

    Analysis Population Description
    Per protocol, this outcome measure was only assessed in the dose escalation dose level 1 and dose escalation dose level 2 groups.
    Arm/Group Title Dose Escalation Dose Level 1 LMB-100 100 mcg/kg Dose Escalation Dose Level 2 LMB-100 140 mcg/kg
    Arm/Group Description LMB-100 100 mcg/kg LMB-100: Arms 1: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 1: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study. LMB-100 140 mcg/kg LMB-100: Arms 2: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 2: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study.
    Measure Participants 7 3
    Count of Participants [Participants]
    1
    14.3%
    2
    66.7%
    4. Secondary Outcome
    Title Percentage of Participants With LMB-100 Plasma Drug Levels Above Threshold 600ng/mL During Cycle 2 in Dose Escalation
    Description This measure assessed how many participants in the dose escalation have LMB-100 plasma drug levels higher than threshold (600 ng/mL) during Cycle 2 pharmacokinetics (PK) measurements, a sign of effective prevention of anti-LMB-100 antibodies. The validated enzyme-linked immunosorbent assay (ELISA) test was used to measure plasma LMB-100 concentration. Below 600ng/mL is considered a bad outcome and above 600ng/mL is considered a good outcome.
    Time Frame Plasma LMB-100 levels during Cycle 2 of treatment (each cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    6/10 participants were not evaluable for this endpoint because they did not receive the second cycle of treatment.
    Arm/Group Title Dose Escalation Dose Level 1 LMB-100 100 mcg/kg Dose Escalation Dose Level 2 LMB-100 140 mcg/kg
    Arm/Group Description LMB-100 100 mcg/kg LMB-100: Arms 1: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 1: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study. LMB-100 140 mcg/kg LMB-100: Arms 2: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 2: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study.
    Measure Participants 4 0
    Number [Percentage of participants]
    75
    1071.4%
    5. Secondary Outcome
    Title Maximum Observed (Peak) Plasma Concentration (Cmax) of LMB-100
    Description The maximum observed analyte concentration in plasma was reported.
    Time Frame Pre-administration, end-of-infusion, then 1, 2, 4, 8-10, 12-16 hours post- LMB-100 during cycle 1 (each cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    1/6 participants from the expansion cohort were not evaluable because they discontinued treatment before receiving LMB-100 during their 1st cycle.
    Arm/Group Title Dose Escalation Dose Level 1 LMB-100 100 mcg/kg Dose Escalation Dose Level 2 LMB-100 140 mcg/kg Dose Expansion LMB-100, 100 mcg/kg
    Arm/Group Description LMB-100 100 mcg/kg LMB-100: Arms 1: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 1: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study. LMB-100 140 mcg/kg LMB-100: Arms 2: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 2: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study. LMB-100 at optimal dose plus tofacitinib - 100 mcg/kg LMB-100: Arms 1: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 1: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study.
    Measure Participants 7 3 5
    Mean (Standard Deviation) [ng/mL]
    1644.43
    (343.08)
    2160.67
    (797.9)
    1466.4
    (257.25)
    6. Secondary Outcome
    Title Percentage of Participants Without Delayed Formation of Neutralizing Anti-LMB-100 Anti-drug Antibodies (ADAs)
    Description This measure assessed how many participants have no LMB-100 plasma drug levels higher than threshold (600 ng/mL) during Cycle 3 pharmacokinetics (PK) measurements, a sign of effective prevention of anti-LMB-100 antibodies. The validated enzyme-linked immunosorbent assay (ELISA) test was used to measure plasma LMB-100 concentration. Below 600ng/mL is considered a bad outcome and above 600ng/mL is considered a good outcome.
    Time Frame Plasma LMB-100 levels during Cycle 3 treatment (each cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    12/16 participants were not evaluable because they did not receive a 3rd cycle of treatment.
    Arm/Group Title Dose Escalation Dose Level 1 LMB-100 100 mcg/kg Dose Escalation Dose Level 2 LMB-100 140 mcg/kg Dose Expansion LMB-100, 100 mcg/kg
    Arm/Group Description LMB-100 100 mcg/kg LMB-100: Arms 1: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 1: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study. LMB-100 140 mcg/kg LMB-100: Arms 2: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 2: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study. LMB-100 at optimal dose plus tofacitinib - 100 mcg/kg LMB-100: Arms 1: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 1: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study.
    Measure Participants 2 1 1
    Number [Percentage of participants]
    100
    1428.6%
    0
    0%
    0
    0%
    7. Secondary Outcome
    Title Area Under the Plasma Concentration vs. Time Curve Extrapolated to Infinity (AUC(INF)) of LMB-100
    Description AUC is a measure of the serum concentration of LMB-100 over time. It is used to characterize drug absorption.
    Time Frame Pre-administration, end-of-infusion, then 1, 2, 4, 8-10, 12-16 hours post- LMB-100 during cycle 1 (each cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    3/16 participants from both cohorts were not analyzed they did not have AUC(INF) of LMB-100 measured during the 1st cycle (i.e., Not evaluable)
    Arm/Group Title Dose Escalation Dose Level 1 LMB-100 100 mcg/kg Dose Escalation Dose Level 2 LMB-100 140 mcg/kg Dose Expansion LMB-100, 100 mcg/kg
    Arm/Group Description LMB-100 100 mcg/kg LMB-100: Arms 1: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 1: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study. LMB-100 140 mcg/kg LMB-100: Arms 2: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 2: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study. LMB-100 at optimal dose plus tofacitinib - 100 mcg/kg LMB-100: Arms 1: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 1: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study.
    Measure Participants 6 2 5
    Mean (Standard Deviation) [h*ng/mL]
    2415.9
    (1041.2)
    2918.5
    (2434.6)
    2804.1
    (190.14)
    8. Secondary Outcome
    Title Plasma Half-Life (T1/2) of LMB-100
    Description Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.
    Time Frame Pre-administration, end-of-infusion, then 1, 2, 4, 8-10, 12-16 hours post- LMB-100 during cycle 1 (each cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    3/16 participants were not analyzed because they did not have Plasma Half-life (T1/2) of LMB-100 measured during the 1st cycle (i.e., Not evaluable).
    Arm/Group Title Dose Escalation Dose Level 1 LMB-100 100 mcg/kg Dose Escalation Dose Level 2 LMB-100 140 mcg/kg Dose Expansion LMB-100, 100 mcg/kg
    Arm/Group Description LMB-100 100 mcg/kg LMB-100: Arms 1: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 1: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study. LMB-100 140 mcg/kg LMB-100: Arms 2: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 2: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study. LMB-100 at optimal dose plus tofacitinib - 100 mcg/kg LMB-100: Arms 1: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 1: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study.
    Measure Participants 6 2 5
    Mean (Standard Deviation) [hour (h)]
    1.0
    (0.39)
    0.8
    (0.22)
    1.2
    (0.25)
    9. Secondary Outcome
    Title Number of Participants With Serious Adverse Events Possibly, Probably, and/or Definitely Related to LMB-100 Who Have Pancreatobiliary Cancer
    Description Grade 1-4 adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 observed in participants with pancreatic cancer. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe or medically significant. Grade 4 is life-threatening consequences. Grade 5 is death related to adverse event.
    Time Frame Throughout study treatment until 30 days post-completion, approximately 13 weeks.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dose Expansion LMB-100, 100 mcg/kg
    Arm/Group Description LMB-100 at optimal dose plus tofacitinib - 100 mcg/kg LMB-100: Arms 1: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 1: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study.
    Measure Participants 6
    Count of Participants [Participants]
    4
    57.1%
    10. Other Pre-specified Outcome
    Title Number of Participants With Serious and/or Non-serious Adverse Events Regardless of Attribution Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).
    Description Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
    Time Frame Throughout study treatment until 30 days post-completion, approximately 13 weeks.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dose Escalation- Dose Level 1 LMB-100 100 mcg/kg Dose Escalation Dose Level 2 LMB-100 140 mcg/kg Dose Expansion LMB-100, 100 mcg/kg
    Arm/Group Description LMB-100 100 mcg/kg LMB-100: Arms 1: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 1: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study. LMB-100 140 mcg/kg LMB-100: Arms 2: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 2: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study. LMB-100 at optimal dose plus tofacitinib - 100 mcg/kg LMB-100: Arms 1: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 1: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study.
    Measure Participants 7 3 6
    Count of Participants [Participants]
    7
    100%
    3
    100%
    6
    100%
    11. Other Pre-specified Outcome
    Title Number of Participants With a Dose-Limiting Toxicity (DLT)
    Description A dose limiting toxicity is defined as any events occurring within the first cycle of treatment (21 days) such as any death not clearly due to the underlying disease or extraneous causes, transaminitis that meets criteria for Hy's Law: grade ≥2 elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) with simultaneous elevation of total bilirubin to ≥ 2x ULN while alkaline phosphatase remains < 2x upper limit of normal (ULN). Some hematological toxicities, and Grade ≥3 non-hematological toxicities; and any other drug related toxicity considered significant enough to be qualifies as a DLT in the opinion of the principal investigator. Inability to start cycle 2 within 2 weeks after completing cycle 1 due to drug-related adverse events.
    Time Frame First cycle (21 days)

    Outcome Measure Data

    Analysis Population Description
    1 of 7 participants in Dose Escalation-Dose Level 1 is not evaluable due to withdrawal from the study with loss of follow-up before the conclusion of the DLT period.
    Arm/Group Title Dose Escalation Dose Level 1 LMB-100 100 mcg/kg Dose Escalation Dose Level 2 LMB-100 140 mcg/kg
    Arm/Group Description LMB-100 100 mcg/kg LMB-100: Arms 1: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 1: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study. LMB-100 140 mcg/kg LMB-100: Arms 2: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 2: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study.
    Measure Participants 6 3
    Count of Participants [Participants]
    0
    0%
    2
    66.7%

    Adverse Events

    Time Frame Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
    Adverse Event Reporting Description
    Arm/Group Title Dose Escalation Dose Level 1 LMB-100 100 mcg/kg Dose Escalation Dose Level 2 LMB-100 140 mcg/kg Dose Expansion LMB-100, 100 mcg/kg
    Arm/Group Description LMB-100 100 mcg/kg LMB-100: Arms 1: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 1: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study. LMB-100 140 mcg/kg LMB-100: Arms 2: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 2: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study. LMB-100 at optimal dose plus tofacitinib - 100 mcg/kg LMB-100 at optimal dose plus tofacitinib LMB-100: Arms 1: Administered intravenous (IV) as an approximate 30-minute infusion of each 21-day cycle on days 4, 6 and 8 until disease progression, intolerance or withdrawal from study. Tofacitinib: Arms 1: Administered orally twice daily on days 1-10 of each cycle until disease progression, intolerance or withdrawal from study.
    All Cause Mortality
    Dose Escalation Dose Level 1 LMB-100 100 mcg/kg Dose Escalation Dose Level 2 LMB-100 140 mcg/kg Dose Expansion LMB-100, 100 mcg/kg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/7 (85.7%) 2/3 (66.7%) 4/6 (66.7%)
    Serious Adverse Events
    Dose Escalation Dose Level 1 LMB-100 100 mcg/kg Dose Escalation Dose Level 2 LMB-100 140 mcg/kg Dose Expansion LMB-100, 100 mcg/kg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/7 (57.1%) 3/3 (100%) 4/6 (66.7%)
    Cardiac disorders
    Atrial fibrillation 0/7 (0%) 0 1/3 (33.3%) 1 1/6 (16.7%) 1
    Myocarditis 0/7 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Pericardial effusion 0/7 (0%) 0 2/3 (66.7%) 2 1/6 (16.7%) 1
    Pericardial tamponade 0/7 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Pericarditis 0/7 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Gastrointestinal disorders
    Nausea 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Small intestinal obstruction 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Vomiting 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    General disorders
    Fever 1/7 (14.3%) 1 0/3 (0%) 0 2/6 (33.3%) 2
    Pain 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Injury, poisoning and procedural complications
    Infusion related reaction 0/7 (0%) 0 0/3 (0%) 0 2/6 (33.3%) 2
    Investigations
    Blood bilirubin increased 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Metabolism and nutrition disorders
    Dehydration 0/7 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Hyponatremia 1/7 (14.3%) 1 1/3 (33.3%) 1 0/6 (0%) 0
    Nervous system disorders
    Encephalopathy 0/7 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Psychiatric disorders
    Confusion 0/7 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Pleural effusion 1/7 (14.3%) 1 0/3 (0%) 0 1/6 (16.7%) 1
    Pulmonary hypertension 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Surgical and medical procedures
    Surgical and medical procedures - Other, Intraoperative complication 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Vascular disorders
    Capillary leak syndrome 0/7 (0%) 0 2/3 (66.7%) 2 0/6 (0%) 0
    Hypotension 0/7 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Other (Not Including Serious) Adverse Events
    Dose Escalation Dose Level 1 LMB-100 100 mcg/kg Dose Escalation Dose Level 2 LMB-100 140 mcg/kg Dose Expansion LMB-100, 100 mcg/kg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/7 (100%) 3/3 (100%) 6/6 (100%)
    Blood and lymphatic system disorders
    Anemia 3/7 (42.9%) 12 2/3 (66.7%) 2 3/6 (50%) 3
    Leukocytosis 1/7 (14.3%) 1 0/3 (0%) 0 1/6 (16.7%) 1
    Cardiac disorders
    Chest pain - cardiac 0/7 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Electrocardiogram QT corrected interval prolonged 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Myocarditis 0/7 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Pericarditis 0/7 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Sinus bradycardia 0/7 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Sinus tachycardia 2/7 (28.6%) 3 2/3 (66.7%) 3 1/6 (16.7%) 1
    Ear and labyrinth disorders
    Tinnitus 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Eye disorders
    Watering eyes 0/7 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Gastrointestinal disorders
    Abdominal distension 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Abdominal pain 2/7 (28.6%) 3 1/3 (33.3%) 1 0/6 (0%) 0
    Ascites 0/7 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 2
    Bloating 1/7 (14.3%) 2 0/3 (0%) 0 0/6 (0%) 0
    Constipation 3/7 (42.9%) 5 0/3 (0%) 0 3/6 (50%) 3
    Diarrhea 1/7 (14.3%) 1 0/3 (0%) 0 1/6 (16.7%) 1
    Dry mouth 0/7 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Gastroesophageal reflux disease 1/7 (14.3%) 2 0/3 (0%) 0 0/6 (0%) 0
    Nausea 3/7 (42.9%) 4 0/3 (0%) 0 1/6 (16.7%) 1
    Vomiting 3/7 (42.9%) 6 1/3 (33.3%) 1 2/6 (33.3%) 2
    General disorders
    Chills 0/7 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Edema limbs 0/7 (0%) 0 0/3 (0%) 0 2/6 (33.3%) 2
    Fatigue 6/7 (85.7%) 6 1/3 (33.3%) 1 4/6 (66.7%) 4
    Fever 1/7 (14.3%) 4 2/3 (66.7%) 2 2/6 (33.3%) 2
    Localized edema 4/7 (57.1%) 4 0/3 (0%) 0 2/6 (33.3%) 4
    Pain 2/7 (28.6%) 4 1/3 (33.3%) 1 2/6 (33.3%) 2
    Immune system disorders
    Immune system disorders - Other, Inflammatory Synovitis 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Infections and infestations
    Biliary tract infection 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Herpes simplex reactivation 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Urinary tract infection 0/7 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Injury, poisoning and procedural complications
    Injury, poisoning and procedural complications - Other, specify 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Investigations
    Activated partial thromboplastin time prolonged 2/7 (28.6%) 2 2/3 (66.7%) 4 1/6 (16.7%) 3
    Alanine aminotransferase increased 5/7 (71.4%) 5 1/3 (33.3%) 1 2/6 (33.3%) 2
    Alkaline phosphatase increased 2/7 (28.6%) 2 0/3 (0%) 0 0/6 (0%) 0
    Aspartate aminotransferase increased 5/7 (71.4%) 10 1/3 (33.3%) 1 2/6 (33.3%) 2
    Blood bilirubin increased 2/7 (28.6%) 9 1/3 (33.3%) 1 1/6 (16.7%) 1
    Blood lactate dehydrogenase increased 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Cardiac troponin I increased 0/7 (0%) 0 1/3 (33.3%) 1 1/6 (16.7%) 1
    Creatinine increased 2/7 (28.6%) 2 0/3 (0%) 0 3/6 (50%) 5
    Ejection fraction decreased 0/7 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Lymphocyte count decreased 4/7 (57.1%) 10 3/3 (100%) 8 3/6 (50%) 4
    Neutrophil count decreased 0/7 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Platelet count decreased 1/7 (14.3%) 1 0/3 (0%) 0 1/6 (16.7%) 1
    Weight gain 1/7 (14.3%) 1 1/3 (33.3%) 4 1/6 (16.7%) 1
    White blood cell decreased 1/7 (14.3%) 2 1/3 (33.3%) 2 0/6 (0%) 0
    Metabolism and nutrition disorders
    Anorexia 0/7 (0%) 0 0/3 (0%) 0 3/6 (50%) 3
    Hypermagnesemia 2/7 (28.6%) 2 0/3 (0%) 0 1/6 (16.7%) 1
    Hyperphosphatemia 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Hypoalbuminemia 5/7 (71.4%) 12 3/3 (100%) 3 4/6 (66.7%) 8
    Hypocalcemia 1/7 (14.3%) 1 1/3 (33.3%) 2 1/6 (16.7%) 1
    Hypokalemia 2/7 (28.6%) 3 0/3 (0%) 0 1/6 (16.7%) 1
    Hyponatremia 4/7 (57.1%) 9 1/3 (33.3%) 3 4/6 (66.7%) 9
    Musculoskeletal and connective tissue disorders
    Back pain 2/7 (28.6%) 2 0/3 (0%) 0 0/6 (0%) 0
    Myalgia 1/7 (14.3%) 1 1/3 (33.3%) 2 1/6 (16.7%) 1
    Pain in extremity 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumor pain 3/7 (42.9%) 3 0/3 (0%) 0 0/6 (0%) 0
    Nervous system disorders
    Dizziness 1/7 (14.3%) 1 0/3 (0%) 0 1/6 (16.7%) 2
    Headache 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Somnolence 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Renal and urinary disorders
    Dysuria 0/7 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Reproductive system and breast disorders
    Pelvic pain 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 2/7 (28.6%) 2 0/3 (0%) 0 2/6 (33.3%) 3
    Nasal congestion 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Pleural effusion 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0
    Skin and subcutaneous tissue disorders
    Skin and subcutaneous tissue disorders - Other, verruca lesion" 0/7 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Vascular disorders
    Capillary leak syndrome 0/7 (0%) 0 2/3 (66.7%) 2 2/6 (33.3%) 2
    Hypotension 1/7 (14.3%) 1 0/3 (0%) 0 3/6 (50%) 4
    Thromboembolic event 1/7 (14.3%) 1 0/3 (0%) 0 0/6 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Christine C. Alewine
    Organization National cancer Institute
    Phone 240-760-6146
    Email christine.alewine@nih.gov
    Responsible Party:
    Christine Alewine, M.D., Principla Investigator, National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT04034238
    Other Study ID Numbers:
    • 190128
    • 19-C-0128
    First Posted:
    Jul 26, 2019
    Last Update Posted:
    Feb 8, 2022
    Last Verified:
    Jan 1, 2022