Phase 1
N=21
Mesothelin-Targeted Immunotoxin LMB-100 in People With Malignant Mesothelioma
Mesothelioma
Bottom Line
View on ClinicalTrials.gov: NCT02798536 ↗Enrolled (actual)
21
Serious AEs
23.8%
Results posted
Aug 2022
Primary outcome: Primary: Recommended Phase 2 Dose (RP2D) of LMB100 + Nab-paclitaxel — 140; 100 mcg
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- LMB-100 (Drug); nab-paclitaxel (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Jul 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Recommended Phase 2 Dose (RP2D) of LMB100 + Nab-paclitaxel |
140; 100 | — |
| SECONDARY Number of Participants at Recommended Phase 2 Dose (RP2D) With Partial or Complete Response by the Response Evaluation Criteria in Solid Tumors (RECIST) |
0; 0; 0; 0 | — |
| SECONDARY Median Progression Free Survival (PFS) |
2.7; 2.7; 2.7 | — |
| SECONDARY Median Overall Survival (OS) |
33.5; 16.9; 10.1 | — |
| SECONDARY Number of Participants With LMB-100 Maximum Observed Serum Concentration (Cmax) of >100ng/mL |
3; 7; 10; 2; 4; 3 | — |
| SECONDARY Number of Participants With Anti-drug Antibodies (ADAs) Formation to LMB-100 |
0; 2; 3; 3; 5; 5 | — |
| SECONDARY Number of Grade 3-5 Adverse Events Possibly, Probably, and/or Definitely Related to the LMB-100 +/- Nab-Paclitaxel |
0; 0; 1; 0; 0; 1 | — |
| SECONDARY Duration of Response (DOR) |
NA; NA; NA | — |
Summary
Background:
LMB-100 is a man-made protein. It is attracted to the mesothelin protein. This is found in many tumors, including mesothelioma. But it is found in only a very small number of normal tissues. After binding to mesothelin on tumors, LMB-100 attacks and kills cancer cells. Researchers want to test LMB-100 in people with advanced mesothelioma.
Objective:
To find a safe dose and anti-tumor activity of LMB-100 for people with advanced mesothelioma.
Eligibility:
Adults ages 18 and older with:
Advanced pleural or peritoneal mesothelioma that has not responded to platinum-based
therapy
Adequate organ function
Design:
Participants will be screened with:
Samples of tumor tissue or tumor fluid. These can be new or from a previous procedure.
Medical history
Physical exam
Blood, urine, and heart tests
Chest x-rays
Computed tomography (CT) or magnetic resonance imaging (MRI) scans
Fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans
Participants will get LMB-100 on days 1, 3, and 5 of each 21-day cycle. It will be given through an intravenous (IV) catheter, a tube inserted in an arm vein. They will get standard medicines before each infusion to help prevent side effects. Each infusion lasts about 30 minutes. They will be monitored for up to 2 hours after.
During each cycle, participants will repeat the screening tests.
Participants will get the study drug for up to 4 cycles or until their disease worsens or they have intolerable side effects.
About 4-6 weeks after their last infusion, participants will have a follow-up visit. They will repeat the study tests.
Participants will have follow-up scans every 6 weeks until their disease gets worse.
Participants will be called about once a year to see how they are doing.
Eligibility Criteria
- INCLUSION CRITERIA (All Cohorts):
- Histologically confirmed epithelial or biphasic mesothelioma not amenable to potentially curative surgical resection. However, patients with biphasic tumors that have a more than or equal to 50% sarcomatoid component will be excluded. The diagnosis will be confirmed by the Laboratory of Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI).
- Archival sample or fresh biopsy or tumor effusion must be available for confirmation of diagnosis.
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to10 mm with spiral computed tomography (CT) scan.
- Patients must have had at least one prior chemotherapy regimen that includes pemetrexed and cisplatin or carboplatin. There is no limit to the number of prior chemotherapy regimens received.
- The last dose of previous therapy must have occurred at least 3 weeks prior to the start of study therapy. Palliative radiotherapy is allowed up to 2 weeks before the first LMB-100 infusion.
- Patients for whom no standard curable therapy exists
- Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of LMB-100 in patients 2.5 mg/dL without intravenous supplementation
- Must have left ventricular ejection fraction > 50%
- Must have an ambulatory oxygen saturation of > 90% on room air
- Women of child-bearing potential (defined as a sexually mature woman who (1) has not undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or; (2) has not been naturally postmenopausal for at least 24 consecutive months [i.e., has had menses at any time during the preceding 24 consecutive months]) must:
- Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis), or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting study therapy (including dose interruptions), while on study medication and for 3 months after the last dose of study therapy; and
- Have a negative serum pregnancy test ( 20 mg of dexamethasone a day (or equivalent) for > 7 consecutive days.
EXCLUSION CRITERIA (Cohort B only)
- Subjects must not have received paclitaxel nor nab-paclitaxel within 4 months prior to initiation of study therapy.
- Participants with contra-indication and/or history of sever hypersensitivity reactions to nab-paclitaxel.
Data sourced from ClinicalTrials.gov (NCT02798536). 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.