Trial Outcomes & Findings for Mesothelin-Targeted Immunotoxin LMB-100 in Combination With Tofacitinib in Persons With Previously Treated Pancreatic Adenocarcinoma, Cholangiocarcinoma and Other Mesothelin Expressing Solid Tumors (NCT NCT04034238)

Last Updated: 2023-08-01

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

19 participants

Primary outcome timeframe

First cycle of treatment (21 days)

Results posted on

2023-08-01

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Dose Escalation- Dose Level 1 LMB-100 100 mcg/kg 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	Dose Escalation- Dose Level 2 - LMB -100 140 mcg/kg 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	Dose Expansion LMB-100 100 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.	Enrolled But Not Treated Participants were enrolled but not treated.
Dose Escalation Phase STARTED	7	3	0	2
Dose Escalation Phase COMPLETED	6	3	0	0
Dose Escalation Phase NOT COMPLETED	1	0	0	2
Dose Expansion Phase STARTED	0	0	6	1
Dose Expansion Phase COMPLETED	0	0	5	0
Dose Expansion Phase NOT COMPLETED	0	0	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose Escalation- Dose Level 1 LMB-100 100 mcg/kg 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	Dose Expansion LMB-100 100 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.	Enrolled But Not Treated Participants were enrolled but not treated.
Dose Escalation Phase Withdrawal by Subject	1	0	0
Dose Escalation Phase Screen failures	0	0	2
Dose Expansion Phase Not treated due to study hold.	0	0	1
Dose Expansion Phase Discontinued treatment before received LMB-100 during first cycle	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Escalation Dose Level 1 LMB-100 100 mcg/kg n=7 Participants 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	Dose Escalation Dose Level 2 LMB-100 140 mcg/kg n=3 Participants 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	Dose Expansion LMB-100, 100 mcg/kg n=6 Participants 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 n=16 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	9 Participants n=4 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	7 Participants n=4 Participants
Age, Continuous	61.79 years STANDARD_DEVIATION 15.99 • n=5 Participants	54.53 years STANDARD_DEVIATION 16.26 • n=7 Participants	70.68 years STANDARD_DEVIATION 11.36 • n=5 Participants	63.76 years STANDARD_DEVIATION 14.79 • n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants	11 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	8 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	13 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	7 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants	16 participants n=4 Participants

PRIMARY outcome

Timeframe: First cycle of treatment (21 days)

Outcome measures

Outcome measures
Measure	All Participants in Dose Escalation Dose Level 1, and Dose Level 2 n=10 Participants 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.	Dose Escalation Dose Level 2 LMB-100 140 mcg/kg 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.	Dose Expansion LMB-100, 100 mcg/kg 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.
Maximum Tolerated Dose (MTD) of LMB-100 With Tofacitinib	100 mcg/kg given days 4, 6, 8 every cycle	—	—

PRIMARY outcome

Timeframe: Plasma LMB-100 levels during Cycle 2 treatment (each cycle = 21 days)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	All Participants in Dose Escalation Dose Level 1, and Dose Level 2 n=6 Participants 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.	Dose Escalation Dose Level 2 LMB-100 140 mcg/kg 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.	Dose Expansion LMB-100, 100 mcg/kg 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.
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 Percentage of participants	—	—

PRIMARY outcome

Timeframe: Throughout study treatment until 30 days post-completion, approximately 13 weeks

Population: Per protocol, this outcome measure was only assessed in the dose escalation dose level 1 and dose escalation dose level 2 groups.

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.

Outcome measures

Outcome measures
Measure	All Participants in Dose Escalation Dose Level 1, and Dose Level 2 n=7 Participants 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.	Dose Escalation Dose Level 2 LMB-100 140 mcg/kg n=3 Participants 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.	Dose Expansion LMB-100, 100 mcg/kg 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.
Number of Participants With Serious Adverse Events Possibly, Probably, and/or Definitely Related to LMB-100 Treated in the Dose Escalation Group	1 Participants	2 Participants	—

SECONDARY outcome

Timeframe: Plasma LMB-100 levels during Cycle 2 of treatment (each cycle = 21 days)

Population: 6/10 participants were not evaluable for this endpoint because they did not receive the second cycle of treatment.

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.

Outcome measures

Outcome measures
Measure	All Participants in Dose Escalation Dose Level 1, and Dose Level 2 n=4 Participants 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.	Dose Escalation Dose Level 2 LMB-100 140 mcg/kg 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.	Dose Expansion LMB-100, 100 mcg/kg 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.
Percentage of Participants With LMB-100 Plasma Drug Levels Above Threshold 600ng/mL During Cycle 2 in Dose Escalation	75 Percentage of participants	—	—

SECONDARY outcome

Timeframe: Pre-administration, end-of-infusion, then 1, 2, 4, 8-10, 12-16 hours post- LMB-100 during cycle 1 (each cycle = 21 days)

Population: 1/6 participants from the expansion cohort were not evaluable because they discontinued treatment before receiving LMB-100 during their 1st cycle.

The maximum observed analyte concentration in plasma was reported.

Outcome measures

Outcome measures
Measure	All Participants in Dose Escalation Dose Level 1, and Dose Level 2 n=7 Participants 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.	Dose Escalation Dose Level 2 LMB-100 140 mcg/kg n=3 Participants 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.	Dose Expansion LMB-100, 100 mcg/kg n=5 Participants 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.
Maximum Observed (Peak) Plasma Concentration (Cmax) of LMB-100	1644.43 ng/mL Standard Deviation 343.08	2160.67 ng/mL Standard Deviation 797.9	1466.4 ng/mL Standard Deviation 257.25

SECONDARY outcome

Timeframe: Plasma LMB-100 levels during Cycle 3 treatment (each cycle = 21 days)

Population: 12/16 participants were not evaluable because they did not receive a 3rd cycle of treatment.

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.

Outcome measures

Outcome measures
Measure	All Participants in Dose Escalation Dose Level 1, and Dose Level 2 n=2 Participants 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.	Dose Escalation Dose Level 2 LMB-100 140 mcg/kg n=1 Participants 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.	Dose Expansion LMB-100, 100 mcg/kg n=1 Participants 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.
Percentage of Participants Without Delayed Formation of Neutralizing Anti-LMB-100 Anti-drug Antibodies (ADAs)	100 Percentage of participants	0 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: Pre-administration, end-of-infusion, then 1, 2, 4, 8-10, 12-16 hours post- LMB-100 during cycle 1 (each cycle = 21 days)

Population: 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)

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

Outcome measures

Outcome measures
Measure	All Participants in Dose Escalation Dose Level 1, and Dose Level 2 n=6 Participants 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.	Dose Escalation Dose Level 2 LMB-100 140 mcg/kg n=2 Participants 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.	Dose Expansion LMB-100, 100 mcg/kg n=5 Participants 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.
Area Under the Plasma Concentration vs. Time Curve Extrapolated to Infinity (AUC(INF)) of LMB-100	2415.9 h*ng/mL Standard Deviation 1041.2	2918.5 h*ng/mL Standard Deviation 2434.6	2804.1 h*ng/mL Standard Deviation 190.14

SECONDARY outcome

Timeframe: Pre-administration, end-of-infusion, then 1, 2, 4, 8-10, 12-16 hours post- LMB-100 during cycle 1 (each cycle = 21 days)

Population: 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).

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

Outcome measures

Outcome measures
Measure	All Participants in Dose Escalation Dose Level 1, and Dose Level 2 n=6 Participants 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.	Dose Escalation Dose Level 2 LMB-100 140 mcg/kg n=2 Participants 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.	Dose Expansion LMB-100, 100 mcg/kg n=5 Participants 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.
Plasma Half-Life (T1/2) of LMB-100	1.0 hour (h) Standard Deviation 0.39	0.8 hour (h) Standard Deviation 0.22	1.2 hour (h) Standard Deviation 0.25

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	All Participants in Dose Escalation Dose Level 1, and Dose Level 2 n=6 Participants 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.	Dose Escalation Dose Level 2 LMB-100 140 mcg/kg 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.	Dose Expansion LMB-100, 100 mcg/kg 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.
Number of Participants With Serious Adverse Events Possibly, Probably, and/or Definitely Related to LMB-100 Who Have Pancreatobiliary Cancer	4 Participants	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	All Participants in Dose Escalation Dose Level 1, and Dose Level 2 n=7 Participants 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.	Dose Escalation Dose Level 2 LMB-100 140 mcg/kg n=3 Participants 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.	Dose Expansion LMB-100, 100 mcg/kg n=6 Participants 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.
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).	7 Participants	3 Participants	6 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: First cycle (21 days)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	All Participants in Dose Escalation Dose Level 1, and Dose Level 2 n=6 Participants 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.	Dose Escalation Dose Level 2 LMB-100 140 mcg/kg n=3 Participants 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.	Dose Expansion LMB-100, 100 mcg/kg 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.
Number of Participants With a Dose-Limiting Toxicity (DLT)	0 Participants	2 Participants	—

Adverse Events

Dose Escalation Dose Level 1 LMB-100 100 mcg/kg

Serious events: 4 serious events

Other events: 7 other events

Deaths: 6 deaths

Dose Escalation Dose Level 2 LMB-100 140 mcg/kg

Serious events: 3 serious events

Other events: 3 other events

Deaths: 2 deaths

Dose Expansion LMB-100, 100 mcg/kg

Serious events: 4 serious events

Other events: 6 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Christine C. Alewine

National cancer Institute

Phone: 240-760-6146

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Dose Escalation Dose Level 1 LMB-100 100 mcg/kg n=7 participants at risk 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.	Dose Escalation Dose Level 2 LMB-100 140 mcg/kg n=3 participants at risk 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.	Dose Expansion LMB-100, 100 mcg/kg n=6 participants at risk 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.
Cardiac disorders Atrial fibrillation	0.00% 0/7 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	33.3% 1/3 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	16.7% 1/6 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
Investigations Blood bilirubin increased	14.3% 1/7 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/3 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/6 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
Vascular disorders Capillary leak syndrome	0.00% 0/7 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	66.7% 2/3 • Number of events 2 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/6 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
Psychiatric disorders Confusion	0.00% 0/7 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/3 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	16.7% 1/6 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
Metabolism and nutrition disorders Dehydration	0.00% 0/7 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	33.3% 1/3 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/6 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
Respiratory, thoracic and mediastinal disorders Dyspnea	14.3% 1/7 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/3 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/6 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
Nervous system disorders Encephalopathy	0.00% 0/7 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	33.3% 1/3 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/6 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
General disorders Fever	14.3% 1/7 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/3 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	33.3% 2/6 • Number of events 2 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
Metabolism and nutrition disorders Hyponatremia	14.3% 1/7 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	33.3% 1/3 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/6 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
Vascular disorders Hypotension	0.00% 0/7 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	33.3% 1/3 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/6 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/7 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/3 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	33.3% 2/6 • Number of events 2 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
Cardiac disorders Myocarditis	0.00% 0/7 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	33.3% 1/3 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/6 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
Gastrointestinal disorders Nausea	14.3% 1/7 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/3 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/6 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
General disorders Pain	14.3% 1/7 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/3 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/6 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
Cardiac disorders Pericardial effusion	0.00% 0/7 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	66.7% 2/3 • Number of events 2 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	16.7% 1/6 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
Cardiac disorders Pericardial tamponade	0.00% 0/7 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/3 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	16.7% 1/6 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
Cardiac disorders Pericarditis	0.00% 0/7 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/3 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	16.7% 1/6 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
Respiratory, thoracic and mediastinal disorders Pleural effusion	14.3% 1/7 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/3 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	16.7% 1/6 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	14.3% 1/7 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/3 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/6 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
Gastrointestinal disorders Small intestinal obstruction	14.3% 1/7 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/3 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/6 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
Surgical and medical procedures Surgical and medical procedures - Other, Intraoperative complication	14.3% 1/7 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/3 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/6 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]
Gastrointestinal disorders Vomiting	14.3% 1/7 • Number of events 1 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/3 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]	0.00% 0/6 • Throughout study treatment until 30 days post-completion, approximately 13 weeks.]