Lymphoma, Solid Tumors
Conditions
Keywords
Topoisomerase I Inhibitor, Epithelial-Mesenchymal Transition, Pharmacodynamics, DNA Damage, Pharmacokinetics
Brief summary
Background: The new drug LMP744 (NSC 706744) damages deoxyribonucleic acid (DNA). This causes cell death. Researchers want to see if it can treat certain kinds of cancer. They want to understand how the drug works and how it affects the body. Objective: To test the safety of LMP744 and find out the dose of the drug that can be safely given to humans. Eligibility: Adults at least 18 years old who have metastatic solid tumors or lymphoma, which have progressed after other treatment. Design: Participants will be screened with: * Vital signs taken * Blood and urine tests * Heart tests * Scans or ultrasound Some participants will have a tumor sample taken 2 times. A small piece of tumor is removed by a small needle. A scan or ultrasound will guide the process. The study will be done in 28-day cycles. Each cycle, participants will get the study drug in a vein for 60 minutes once a day for 5 days. For day 1 of cycle 1, participants will be admitted to the clinic and have blood and urine taken several times. At the beginning of each cycle, participants will have a clinic visit and repeat some screening tests. They will also do this twice in the middle of cycle 1 and once in the middle of cycle 2. After participants stop taking the study drug, they will be followed for 30 days. They may give blood samples. They will be contacted by phone to see how they are doing....
Detailed description
Background: * Indenoisoquinolines are non-camptothecin inhibitors of topoisomerase 1 (top1) with improved characteristics over their predecessors. Indenoisoquinolines have better chemical stability, producing stable deoxyribonucleic acid (DNA)-top1 cleavage complexes, and exhibit a preference for unique DNA cleavage sites, compared with their camptothecin counterparts. * They have demonstrated activity against camptothecin-resistant cell lines and produce DNA-protein crosslinks, which are resistant to reversal. They also show less or no resistance to cells overexpressing the ATP-binding cassette (ABC) transporters, ATP-binding cassette super-family G member 2 (ABCG2), and multidrug resistance (MDR-1). Primary Objectives: -To establish the safety, tolerability and the maximum tolerated dose (MTD) of LMP744 (NSC 706744) administered intravenously (IV) daily for 5 days every day (QD) x 5) schedule in patients with refractory solid tumors and lymphomas. Secondary Objectives: -Characterize the pharmacokinetic (PK) profile of LMP744. Exploratory Objectives: * Evaluate the effect of LMP744 on markers of DNA damage phosphorylated H2AX (γH2AX), phosphorylated Nijmegen breakage syndrome 1 (pNbs1), pATR, excision repair cross-complementation group 1 (ERCC1), RAD51 recombinase (RAD51), Topo1cc, topoisomerase 1 (Top1), Schlafen family member 11 (SLFN11) and epithelial-mesenchymal transition (EMT) in circulating tumor cells (CTCs) and pre- and post- treatment tumor biopsies in patients at the expansion cohort. * Assess preliminary antitumor activity of LMP744. * Examine genomic alterations in circulating tumor DNA (ctDNA) that may be associated with response or resistance to treatment Eligibility: -Adult patients must have histologically documented, relapsed solid tumors which have progressed after one line of therapy, or lymphoma which has progressed after initial therapy and without potentially curative options, or patient refuses potentially curative therapy. Study Design: * Cycle 1 and subsequent cycles: Patients will receive LMP744 administered IV QD over 1 hour on days 1-5 followed by 23 days without drug (28-day cycle). * Pharmacokinetic (PK) and pharmacodynamic (PD) samples will be collected. Tumor biopsies will be mandatory during the expansion phase. LMP744 will be administered IV over 1 hour on days 1-5 of each 28-day cycle. Blood samples for PK analyses will be collected at the following timepoints in cycle 1 only: Day 1, prior to drug administration, 2 minutes (+/- 2 minutes) before end of infusion, and at appropriate time points post infusion (15 minutes, 30 minutes, and 1, 2, 4, and 6 hours post infusion) Day 2, 24-hour (hr) post day 1 start of infusion (prior to day 2 infusion), and 2 minutes (+/- 2 minutes) before the end of infusion Day 3, 24 hr post day 2 start of infusion (prior to day 3 infusion), and 2 minutes (+/- 2 minutes) before end of infusion Day 4, 24 hr post day 3 start of infusion (prior to day 4 infusion), and 2 minutes (+/- 2 minutes) before end of infusion Day 5, 24 hr post day 4 start of infusion (prior to day 5 infusion), and 2 minutes (+/- 2 minutes) before end of infusion Day 8, 72 hr post day 5 start of infusion Blood for circulating tumor cells (CTCs) (optional) will be collected at baseline, on day 3 of Cycle 1 (within 2 to 4 hours after the start of LMP744 infusion), on day 1 of every subsequent cycle (prior to drug infusion), and at disease progression. Tumor biopsies (mandatory in expansion phase) will be obtained at baseline and then on day 2 (1-4 hours after the LMP744 infusion) in cycle 1 only.
Interventions
DRUGLMP744
Indenoisoquinolines, such as LMP744, are potent inhibitors of the enzyme topoisomerase I (Top1). Top1 is necessary for transcription, replication, recombination, and the repair of double-strand deoxyribonucleic acid (DNA) breaks. It relaxes the supercoiled DNA by introducing a single-strand break, generating a free strand that rotates around the Top1-bound DNA complex. In the absence of external triggers, Top1-DNA cleavage complexes are generally short lived. Top1 inhibitors are potent anticancer agents because they stabilize the formation of the Top1-DNA cleavage complex in tumor cells, which induces DNA damage, delays DNA repair, and results in cell cycle arrest and apoptosis. LMP744 exhibited antitumor activity with lower toxicity than other agents in preclinical studies. Treatment of patients with LMP744 is expected to reduce tumor burden at doses that are well-tolerated.
OTHEROndansetron
Anti-emetic for nausea or vomiting.
OTHEROlanzapine
Persistent nausea or vomiting.
OTHERLorazepam
Persistent nausea or vomiting.
OTHERDiphenoxylate hydrocholoride (HCL) + Atropine Sulfate
Diphenoxylate hydrocholoride (HCL) 2.5 mg + Atropine Sulfate 0.025 mg/tablet for diarrhea.
OTHERLoperamide
Antidiarrheal. 4mg by mouth (PO) after first unformed stool and 2mg PO every 2 hours as long as unformed stools continue. No more than 16mg during a 24-hour period.
OTHERDiphenhydramine
Diphenhydramine 50 mg intravenous (IV) for allergic reaction.
OTHERSteroid
For allergic reaction at discretion of principal investigator.
OTHEREpinephrine
For allergic reaction at discretion of principal investigator.
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: 1. Patients must have histologically documented metastatic solid tumors which have progressed after one line of therapy, or lymphoma which has progressed after initial therapy and without potentially curative options, or patient refuses potentially curative therapy. 2. Patients must have measurable or evaluable disease 3. Age greater than or equal to 18 years. 4. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 5. Life expectancy of greater than 3 months. 6. Patients must have normal organ and marrow function as defined below: leukocytes greater than or equal to 3,000/mcL absolute neutrophil count greater than or equal to 1,500/mcL platelets greater than or equal to 100,000/mcL total bilirubin within normal institutional limits Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/ alanine aminotransferase (ALT) serum glutamate-pyruvate transaminase (SGPT) less than or equal to 2.5 institutional upper limit of normal (ULN) Serum creatinine less than or equal to 1.5 institutional ULN OR creatinine clearance greater than or equal to 60 mL/min/1.73 m\^2 for patients with serum creatinine levels greater than 1.5 x higher than institutional normal. 7. Anticoagulation with low-molecular-weight heparin (LMWH) or any direct oral anticoagulant (direct oral anticoagulants (DOAC), e.g., rivaroxaban, apixaban, dabigatran, or edoxaban) will be permitted. Patients receiving treatment with warfarin will be given the option to switch to LMWH or a DOAC. 8. Patients must have recovered to grade 1 or baseline from adverse events (AEs) and/or toxicity of prior chemotherapy or biologic therapy. They must not have had chemotherapy, biologic therapy, or definitive radiotherapy within 4 weeks (6 weeks for nitrosoureas and mitomycin C) or 5 half-lives, whichever is shorter, prior to entering the study. Palliative-intent radiotherapy (30 Gray (Gy) or less) must be completed at least 2 weeks prior to start of treatment and may not be to a lesion that is included as measurable disease. Patients must be greater than or equal to 2 weeks since any investigational agent administered as part of a Phase 0 study (where a sub-therapeutic dose of drug is administered) at the PI's discretion and should have recovered to grade 1 or baseline from any toxicities. 9. Patients receiving denosumab or bisphosphonates for any cancer or undergoing androgen deprivation therapy for prostate cancer are eligible for this therapy. 10. Prior therapy with topoisomerase I inhibitors is allowed. 11. Patients with known human immunodeficiency virus (HIV)-positive status are eligible provided the following criteria are met: cluster of differentiation 4 (CD4) count \>350/mm\^3, an undetectable viral load, and not receiving prophylaxis antibiotics. Diagnostic HIV testing will not be performed during screening or throughout this study. 12. The effects of LMP744 (NSC 706744) 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 and for the duration of study participation. 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. Women and men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of LMP744 administration. 13. Ability to understand and the willingness to sign a written informed consent document. 14. Willingness to provide blood and new tumor biopsy samples for research purposes if on the expansion phase of the study.
Exclusion criteria
1. Patients who are receiving any other investigational agents. 2. Patients with clinically significant illnesses which would compromise participation in the study, including, but not limited to active or uncontrolled infection, immune deficiencies, Hepatitis B, Hepatitis C, uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 3. Patients with known brain metastases or carcinomatous meningitis are excluded from this clinical trial, with the exception of patients whose brain metastatic disease status has remained stable for greater than or equal to 1 month after treatment of the brain metastases. Patients on anti-seizure medications or steroid therapy may be enrolled at the discretion of the Principal Investigator. 4. Pregnant women are excluded from this study because LMP744 is an agent with the potential for 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 LMP744, breastfeeding should be discontinued if the mother is treated. INCLUSION OF WOMEN AND MINORITIES: Both men and women of all races and ethnic groups are eligible for this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation Phase: Maximum Tolerated Dose (MTD) of LMP744 (NSC 706744) | Cycle 1 (28 days) | Maximum tolerated dose (MTD) of LMP744 administered intravenously (IV) daily for 5 days (QD x 5) schedule in participants with refractory solid tumors and lymphomas. The MTD is the dose level at which no more than 1 in 6 participants experience dose-limiting toxicity (DLT), and the dose below that at which ≥ 2 (of ≤ 6) participants have DLT as a result of the drug. A DLT is Grade ≥3 non-hematologic toxicity except Grade 3 fatigue lasting ≤ 7 days. Grade 4 hematological toxicity if it meets the following criteria: Lymphopenia (any grade) will not be considered dose limiting for all participants; Anemia: Grade 4 anemia will be considered dose limiting. Any neurotoxicity Grade ≥2 that is not reversible to a Grade ≤1 within 2 weeks. Any non-hematologic Grade 2 toxicity that does not resolve to Grade ≤1 or baseline within 14 days despite adequate treatment, except for alopecia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation & Dose Expansion Phase: Area Under the Plasma Concentration vs. Time Curve Extrapolated to Infinity (AUC(INF) of LMP744 (NSC 706744) | Day 1, prior to drug administration, 2 minutes before end of infusion; 15 minutes, 30 minutes, and 1, 2, 4, and 6 hours post infusion on Day 1 and prior to start of infusion on Day 2. | AUC is a measure of the serum concentration of LMP744 over time. It is used to characterize drug absorption. |
| Dose Escalation & Dose Expansion Phase: Apparent Half-Life of LMP744 (NSC 706744) | Day 1, prior to drug administration, 2 minutes before end of infusion; 15 minutes, 30 minutes, and 1, 2, 4, and 6 hours post infusion on Day 1 and prior to start of infusion on Day 2. | Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half. |
| Dose Escalation & Dose Expansion Phase: Time to Maximum (Tmax) Concentration of LMP744 (NSC 706744) | Day(D)1, prior to drug administration, 2 minutes (min) before end of infusion; 15 min., 30 min., and 1, 2, 4, and 6 hours (hr) post infusion on D1. 24 hrs post D2, 3, & 4 start of infusion & 2 min. before end of infusion. 72 hrs post D5 start of infusion. | Time to maximum (Tmax) concentration of LMP744 (NSC 706744). |
| Dose Escalation & Dose Expansion Phase: Maximum Concentration of LMP744 (NSC 706744) | Day(D)1, prior to drug administration, 2 minutes (min) before end of infusion; 15 min., 30 min., and 1, 2, 4, and 6 hours (hr) post infusion on D1. 24 hrs post D2, 3, & 4 start of infusion & 2 min. before end of infusion. 72 hrs post D5 start of infusion. | To determine the maximum observed plasma concentration of LMP744, blood samples will be collected from participants and analyzed using a validated liquid chromatography-mass spectrometry (LC-MS) or liquid Chromatography with tandem mass spectrometry (LC-MS-MS) method and calculated by non-compartmental analysis. |
| Dose Escalation & Dose Expansion Phase: Percent Change in End of Infusion Concentration of LMP744 (NSC 706744) | Day 1 at end of infusion to Day 5 end of infusion. | Percent change in end of infusion drug concentration is a measure of LMP744 (NSC 706744) accumulation in the bloodstream from Day 1 to Day 5. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Phosphorylated Form of Gamma H2A Histone Family Member X (γH2AX) Staining | Baseline (pre-treatment) and Cycle 1 Day 1 at 1-4 hours after the end of the LMP744 (NSC 706744) infusion. | Levels of γH2AX in paired pre-treatment and on-treatment tumor biopsies were quantified in response to treatment with LMP744 (NSC 706744) |
| Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Cycle 1 (28 days) | Toxicity was assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A DLT is Grade ≥3 non-hematologic toxicity except Grade 3 fatigue lasting ≤ 7 days. Grade 4 hematological toxicity if it meets the following criteria: Lymphopenia (any grade) will not be considered dose limiting for all participants; Anemia: Grade 4 anemia will be considered dose limiting. Any neurotoxicity Grade ≥2 that is not reversible to a Grade ≤1 within 2 weeks will be considered dose limiting. Any non-hematologic Grade 2 toxicity that does not resolve to Grade ≤1 or baseline within 14 days despite adequate treatment, except for alopecia. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event. |
| Dose Escalation & Dose Expansion Phase: Percentage of Participants With Confirmed Objective Response Following Treatment With LMP744 (NSC 706744) | Tumor re-staging was performed every 2 cycles for the first year on study then every 3 cycles thereafter until a participant met criteria to be removed from the study; a median of 2 cycles completed and a full range of 0-31 cycles completed. | Antitumor activity is evaluated using the rate of confirmed objective responses according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria (i.e., at least a 30% decrease in the sum of the diameters of target lesions compared to the sum of baseline diameters). |
| Dose Escalation & Dose Expansion Phase: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | From first drug administration through 30 days after the last dose of study drug is administered, an average of 12.9 months. | Here is the number of participants with serious and/or 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. |
| Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Cycle 1 (28 days) | Toxicity was assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A DLT is Grade ≥3 non-hematologic toxicity except Grade 3 fatigue lasting ≤ 7 days. Grade 4 hematological toxicity if it meets the following criteria: Lymphopenia (any grade) will not be considered dose limiting for all participants; Anemia: Grade 4 anemia will be considered dose limiting. Any neurotoxicity Grade ≥2 that is not reversible to a Grade ≤1 within 2 weeks will be considered dose limiting. Any non-hematologic Grade 2 toxicity that does not resolve to Grade ≤1 or baseline within 14 days despite adequate treatment, except for alopecia. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event. |
| Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Phosphorylated Nibrin (pNbs1) Staining | Baseline (pre-treatment) and Cycle 1 Day 1 at 1-4 hours after the end of the LMP744 (NSC 706744) infusion. | Levels of pNbs1 in paired pre-treatment and on-treatment tumor biopsies were quantified in response to treatment with LMP744 (NSC 706744) |
| Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for RAD Recombinase (Rad51) Staining | Baseline (pre-treatment) and Cycle 1 Day 1 at 1-4 hours after the end of the LMP744 (NSC 706744) infusion. | Levels of Rad51 in paired pre-treatment and on-treatment tumor biopsies were quantified in response to treatment with LMP744 (NSC 706744) |
| Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Topoisomerase I (Top1) Staining | Baseline (pre-treatment) and Cycle 1 Day 1 at 1-4 hours after the end of the LMP744 (NSC 706744) infusion. | Levels of Top1 in paired pre-treatment and on-treatment tumor biopsies were quantified in response to treatment with LMP744 (NSC 706744) |
| Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Phosphorylated Krüppel Associated Box (KRAB) Domain-Associated Protein 1 (pKap1) Staining | Baseline (pre-treatment) and Cycle 1 Day 1 at 1-4 hours after the end of the LMP744 (NSC 706744) infusion. | Levels of pKap1 in paired pre-treatment and on-treatment tumor biopsies were quantified in response to treatment with LMP744 (NSC 706744) |
| Dose Expansion Phase: Percent Change of Nuclei With ≥19 Topoisomerase 1 Cleavage Complex (Top1cc) Foci in Paired Biopsies | Baseline (pre-treatment) and Cycle 1 Day 1 at 1-4 hours after the end of the LMP744 (NSC 706744) infusion. | Percent of nuclei with ≥19 Top1cc foci in paired pre-treatment and on-treatment tumor biopsies were quantified in response to treatment with LMP744 (NSC 706744) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Trmt) Assignment (Assign.) 1: LMP744 (MJ-III65 Hydrochloride) 6mg/m^2 Participants with metastatic solid tumors that have progressed after one line of therapy, or lymphoma that has progressed after all therapy. LMP744 (MJ-III65 hydrochloride) 6mg/m\^2 intravenous over 1 hour on days 1-5 of each 28 day cycle. | 1 |
| Treatment Assignment 2: LMP744 (MJ-III65 Hydrochloride) 12mg/m^2 Participants with metastatic solid tumors that have progressed after one line of therapy, or lymphoma that has progressed after all therapy. LMP744 (MJ-III65 hydrochloride) 12mg/m\^2 intravenous over 1 hour on days 1-5 of each 28 day cycle. | 1 |
| Treatment Assignment 3: LMP744 (MJ-III65 Hydrochloride) 24mg/m^2 Participants with metastatic solid tumors that have progressed after one line of therapy, or lymphoma that has progressed after all therapy. LMP744 (MJ-III65 hydrochloride) 24mg/m\^2 intravenous over 1 hour on days 1-5 of each 28 day cycle. | 3 |
| Treatment Assignment 4: LMP744 (MJ-III65 Hydrochloride) 48mg/m^2 Participants with metastatic solid tumors that have progressed after one line of therapy, or lymphoma that has progressed after all therapy. LMP744 (MJ-III65 hydrochloride) 48mg/m\^2 intravenous over 1 hour on days 1-5 of each 28 day cycle. | 1 |
| Treatment Assignment 5: LMP744 (MJ-III65 Hydrochloride) 96mg/m^2 Participants with metastatic solid tumors that have progressed after one line of therapy, or lymphoma that has progressed after all therapy. LMP744 (MJ-III65 hydrochloride) 96mg/m\^2 intravenous over 1 hour on days 1-5 of each 28 day cycle. | 1 |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Participants with metastatic solid tumors that have progressed after one line of therapy, or lymphoma that has progressed after all therapy. LMP744 (MJ-III65 hydrochloride) 190mg/m\^2 intravenous over 1 hour on days 1-5 of each 28 day cycle. | 14 |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 Participants with metastatic solid tumors that have progressed after one line of therapy, or lymphoma that has progressed after all therapy. LMP744 (MJ-III65 hydrochloride) 190mg/m\^2 intravenous over 1 hour on days 1-5 followed by 96mg/m\^2 intravenous over 1 hour on days 1-5 of each 28 day cycle. | 2 |
| Trmt Assign. 6:LMP744 190mg/m^2 Foll. by Trmt Assign. 5: 96mg/m^2 Foll. by Trmt Assign. 4: 48mg/m^2 Participants with metastatic solid tumors that have progressed after one line of therapy, or lymphoma that has progressed after all therapy. LMP744 (MJ-III65 hydrochloride) 190mg/m\^2 intravenous over 1 hour on days 1-5 followed by 96mg/m\^2 intravenous over 1 hour on days 1-5 followed by 48mg/m\^2 intravenous over 1 hour on days 1-5 of each 28 day cycle. | 1 |
| Treatment Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 Participants with metastatic solid tumors that have progressed after one line of therapy, or lymphoma that has progressed after all therapy. LMP744 (MJ-III65 hydrochloride) 260mg/m\^2 intravenous over 1 hour on days 1-5 of each 28 day cycle. | 10 |
| Trmt Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 Followed by Trmt Assign. 6: 190mg/m^2 Participants with metastatic solid tumors that have progressed after one line of therapy, or lymphoma that has progressed after all therapy. LMP744 (MJ-III65 hydrochloride) 260mg/m\^2 intravenous over 1 hour on days 1-5 followed by 190mg/m\^2 intravenous over 1 hour on days 1-5 of each 28 day cycle. | 1 |
| Enrolled But Not Treated Participant was enrolled but not treated. | 1 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Dose Expansion | Disease progression before treatment | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Treatment Assignment 2: LMP744 (MJ-III65 Hydrochloride) 12mg/m^2 | Treatment Assignment 3: LMP744 (MJ-III65 Hydrochloride) 24mg/m^2 | Treatment Assignment 4: LMP744 (MJ-III65 Hydrochloride) 48mg/m^2 | Treatment Assignment 5: LMP744 (MJ-III65 Hydrochloride) 96mg/m^2 | Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Trmt Assign. 6:LMP744 190mg/m^2 Foll. by Trmt Assign. 5: 96mg/m^2 Foll. by Trmt Assign. 4: 48mg/m^2 | Treatment Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 | Trmt Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 Followed by Trmt Assign. 6: 190mg/m^2 | Enrolled But Not Treated | Total | Treatment (Trmt) Assignment (Assign.) 1: LMP744 (MJ-III65 Hydrochloride) 6mg/m^2 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 7 Participants | 0 Participants | 0 Participants | 4 Participants | 1 Participants | 0 Participants | 15 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 7 Participants | 2 Participants | 1 Participants | 6 Participants | 0 Participants | 1 Participants | 21 Participants | 1 Participants |
| Age, Continuous | 79 years STANDARD_DEVIATION 0 | 55.67 years STANDARD_DEVIATION 8.96 | 81 years STANDARD_DEVIATION 0 | 39 years STANDARD_DEVIATION 0 | 62.57 years STANDARD_DEVIATION 12.18 | 49 years STANDARD_DEVIATION 19.8 | 46 years STANDARD_DEVIATION 0 | 61.1 years STANDARD_DEVIATION 8.96 | 72 years STANDARD_DEVIATION 0 | 43 years STANDARD_DEVIATION 0 | 60.03 years STANDARD_DEVIATION 12.65 | 49 years STANDARD_DEVIATION 0 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 12 Participants | 1 Participants | 1 Participants | 10 Participants | 1 Participants | 1 Participants | 32 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 6 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 11 Participants | 2 Participants | 1 Participants | 7 Participants | 1 Participants | 1 Participants | 29 Participants | 1 Participants |
| Region of Enrollment United States | 1 participants | 3 participants | 1 participants | 1 participants | 14 participants | 2 participants | 1 participants | 10 participants | 1 participants | 1 participants | 36 participants | 1 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 4 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 9 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 10 Participants | 0 Participants | 1 Participants | 9 Participants | 1 Participants | 1 Participants | 27 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 0 / 1 | 1 / 3 | 0 / 1 | 1 / 1 | 0 / 14 | 0 / 2 | 0 / 1 | 3 / 10 | 0 / 1 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 3 / 3 | 1 / 1 | 1 / 1 | 14 / 14 | 2 / 2 | 1 / 1 | 10 / 10 | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 | 0 / 1 | 1 / 3 | 0 / 1 | 1 / 1 | 9 / 14 | 2 / 2 | 0 / 1 | 4 / 10 | 0 / 1 |
Outcome results
Primary
Dose Escalation Phase: Maximum Tolerated Dose (MTD) of LMP744 (NSC 706744)
Maximum tolerated dose (MTD) of LMP744 administered intravenously (IV) daily for 5 days (QD x 5) schedule in participants with refractory solid tumors and lymphomas. The MTD is the dose level at which no more than 1 in 6 participants experience dose-limiting toxicity (DLT), and the dose below that at which ≥ 2 (of ≤ 6) participants have DLT as a result of the drug. A DLT is Grade ≥3 non-hematologic toxicity except Grade 3 fatigue lasting ≤ 7 days. Grade 4 hematological toxicity if it meets the following criteria: Lymphopenia (any grade) will not be considered dose limiting for all participants; Anemia: Grade 4 anemia will be considered dose limiting. Any neurotoxicity Grade ≥2 that is not reversible to a Grade ≤1 within 2 weeks. Any non-hematologic Grade 2 toxicity that does not resolve to Grade ≤1 or baseline within 14 days despite adequate treatment, except for alopecia.
Time frame: Cycle 1 (28 days)
Population: A total of 27/27 participants were analyzed: 27/27 participants who received LMP744 in the Escalation phase were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Dose Escalation Phase: Maximum Tolerated Dose (MTD) of LMP744 (NSC 706744) | 190 mg/m^2 |
Secondary
Dose Escalation & Dose Expansion Phase: Apparent Half-Life of LMP744 (NSC 706744)
Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half.
Time frame: Day 1, prior to drug administration, 2 minutes before end of infusion; 15 minutes, 30 minutes, and 1, 2, 4, and 6 hours post infusion on Day 1 and prior to start of infusion on Day 2.
Population: A total of 20/36 participants were analyzed: samples from 20/36 participants who had blood collected for pharmacokinetic analyses were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Dose Escalation & Dose Expansion Phase: Apparent Half-Life of LMP744 (NSC 706744) | 0.22 Hours | — |
| Treatment Assignment 2: LMP744 (MJ-III65 Hydrochloride) 12mg/m^2 | Dose Escalation & Dose Expansion Phase: Apparent Half-Life of LMP744 (NSC 706744) | 0.52 Hours | — |
| Treatment Assignment 3: LMP744 (MJ-III65 Hydrochloride) 24mg/m^2 | Dose Escalation & Dose Expansion Phase: Apparent Half-Life of LMP744 (NSC 706744) | 3.54 Hours | Standard Deviation 0.91 |
| Treatment Assignment 4: LMP744 (MJ-III65 Hydrochloride) 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Apparent Half-Life of LMP744 (NSC 706744) | 4.66 Hours | — |
| Treatment Assignment 5: LMP744 (MJ-III65 Hydrochloride) 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Apparent Half-Life of LMP744 (NSC 706744) | 16.2 Hours | — |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Apparent Half-Life of LMP744 (NSC 706744) | 12.59 Hours | Standard Deviation 5.11 |
| Treatment Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 | Dose Escalation & Dose Expansion Phase: Apparent Half-Life of LMP744 (NSC 706744) | 5.79 Hours | Standard Deviation 3.3 |
Secondary
Dose Escalation & Dose Expansion Phase: Area Under the Plasma Concentration vs. Time Curve Extrapolated to Infinity (AUC(INF) of LMP744 (NSC 706744)
AUC is a measure of the serum concentration of LMP744 over time. It is used to characterize drug absorption.
Time frame: Day 1, prior to drug administration, 2 minutes before end of infusion; 15 minutes, 30 minutes, and 1, 2, 4, and 6 hours post infusion on Day 1 and prior to start of infusion on Day 2.
Population: A total of 20/36 participants were analyzed: samples from 20/36 participants who had blood collected for pharmacokinetic analyses were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Dose Escalation & Dose Expansion Phase: Area Under the Plasma Concentration vs. Time Curve Extrapolated to Infinity (AUC(INF) of LMP744 (NSC 706744) | 37.1 ng/mL x h | — |
| Treatment Assignment 2: LMP744 (MJ-III65 Hydrochloride) 12mg/m^2 | Dose Escalation & Dose Expansion Phase: Area Under the Plasma Concentration vs. Time Curve Extrapolated to Infinity (AUC(INF) of LMP744 (NSC 706744) | 50.7 ng/mL x h | — |
| Treatment Assignment 3: LMP744 (MJ-III65 Hydrochloride) 24mg/m^2 | Dose Escalation & Dose Expansion Phase: Area Under the Plasma Concentration vs. Time Curve Extrapolated to Infinity (AUC(INF) of LMP744 (NSC 706744) | 198 ng/mL x h | Standard Deviation 54 |
| Treatment Assignment 4: LMP744 (MJ-III65 Hydrochloride) 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Area Under the Plasma Concentration vs. Time Curve Extrapolated to Infinity (AUC(INF) of LMP744 (NSC 706744) | 462 ng/mL x h | — |
| Treatment Assignment 5: LMP744 (MJ-III65 Hydrochloride) 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Area Under the Plasma Concentration vs. Time Curve Extrapolated to Infinity (AUC(INF) of LMP744 (NSC 706744) | 1858 ng/mL x h | — |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Area Under the Plasma Concentration vs. Time Curve Extrapolated to Infinity (AUC(INF) of LMP744 (NSC 706744) | 5752 ng/mL x h | Standard Deviation 5251 |
| Treatment Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 | Dose Escalation & Dose Expansion Phase: Area Under the Plasma Concentration vs. Time Curve Extrapolated to Infinity (AUC(INF) of LMP744 (NSC 706744) | 4928 ng/mL x h | Standard Deviation 2174 |
Secondary
Dose Escalation & Dose Expansion Phase: Maximum Concentration of LMP744 (NSC 706744)
To determine the maximum observed plasma concentration of LMP744, blood samples will be collected from participants and analyzed using a validated liquid chromatography-mass spectrometry (LC-MS) or liquid Chromatography with tandem mass spectrometry (LC-MS-MS) method and calculated by non-compartmental analysis.
Time frame: Day(D)1, prior to drug administration, 2 minutes (min) before end of infusion; 15 min., 30 min., and 1, 2, 4, and 6 hours (hr) post infusion on D1. 24 hrs post D2, 3, & 4 start of infusion & 2 min. before end of infusion. 72 hrs post D5 start of infusion.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Dose Escalation & Dose Expansion Phase: Maximum Concentration of LMP744 (NSC 706744) | 48.4 ng/mL | — |
| Treatment Assignment 2: LMP744 (MJ-III65 Hydrochloride) 12mg/m^2 | Dose Escalation & Dose Expansion Phase: Maximum Concentration of LMP744 (NSC 706744) | 69.6 ng/mL | — |
| Treatment Assignment 3: LMP744 (MJ-III65 Hydrochloride) 24mg/m^2 | Dose Escalation & Dose Expansion Phase: Maximum Concentration of LMP744 (NSC 706744) | 78.1 ng/mL | Standard Deviation 49.6 |
| Treatment Assignment 4: LMP744 (MJ-III65 Hydrochloride) 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Maximum Concentration of LMP744 (NSC 706744) | 446 ng/mL | — |
| Treatment Assignment 5: LMP744 (MJ-III65 Hydrochloride) 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Maximum Concentration of LMP744 (NSC 706744) | 433.1 ng/mL | — |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Maximum Concentration of LMP744 (NSC 706744) | 1735.4 ng/mL | Standard Deviation 1188.9 |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Maximum Concentration of LMP744 (NSC 706744) | 861.0 ng/mL | Standard Deviation 108.9 |
| Trmt Assign. 6:LMP744 190mg/m^2 Foll. by Trmt Assign. 5: 96mg/m^2 Foll. by Trmt Assign. 4: 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Maximum Concentration of LMP744 (NSC 706744) | 839.0 ng/mL | — |
| Treatment Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 | Dose Escalation & Dose Expansion Phase: Maximum Concentration of LMP744 (NSC 706744) | 1560.9 ng/mL | Standard Deviation 605.5 |
| Trmt Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 Followed by Trmt Assign. 6: 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Maximum Concentration of LMP744 (NSC 706744) | 1160.1 ng/mL | — |
Secondary
Dose Escalation & Dose Expansion Phase: Percent Change in End of Infusion Concentration of LMP744 (NSC 706744)
Percent change in end of infusion drug concentration is a measure of LMP744 (NSC 706744) accumulation in the bloodstream from Day 1 to Day 5.
Time frame: Day 1 at end of infusion to Day 5 end of infusion.
Population: A total of 20/36 participants were analyzed: samples from 20/36 participants who had blood collected for pharmacokinetic analyses were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Dose Escalation & Dose Expansion Phase: Percent Change in End of Infusion Concentration of LMP744 (NSC 706744) | 8.8 Percent change | — |
| Treatment Assignment 2: LMP744 (MJ-III65 Hydrochloride) 12mg/m^2 | Dose Escalation & Dose Expansion Phase: Percent Change in End of Infusion Concentration of LMP744 (NSC 706744) | 33.2 Percent change | — |
| Treatment Assignment 3: LMP744 (MJ-III65 Hydrochloride) 24mg/m^2 | Dose Escalation & Dose Expansion Phase: Percent Change in End of Infusion Concentration of LMP744 (NSC 706744) | 6.9 Percent change | Standard Deviation 35.6 |
| Treatment Assignment 4: LMP744 (MJ-III65 Hydrochloride) 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Percent Change in End of Infusion Concentration of LMP744 (NSC 706744) | 20.1 Percent change | — |
| Treatment Assignment 5: LMP744 (MJ-III65 Hydrochloride) 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Percent Change in End of Infusion Concentration of LMP744 (NSC 706744) | 41.6 Percent change | — |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Percent Change in End of Infusion Concentration of LMP744 (NSC 706744) | -14.1 Percent change | Standard Deviation 43 |
| Treatment Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 | Dose Escalation & Dose Expansion Phase: Percent Change in End of Infusion Concentration of LMP744 (NSC 706744) | 25.8 Percent change | Standard Deviation 10.4 |
Secondary
Dose Escalation & Dose Expansion Phase: Time to Maximum (Tmax) Concentration of LMP744 (NSC 706744)
Time to maximum (Tmax) concentration of LMP744 (NSC 706744).
Time frame: Day(D)1, prior to drug administration, 2 minutes (min) before end of infusion; 15 min., 30 min., and 1, 2, 4, and 6 hours (hr) post infusion on D1. 24 hrs post D2, 3, & 4 start of infusion & 2 min. before end of infusion. 72 hrs post D5 start of infusion.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | Dose Escalation & Dose Expansion Phase: Time to Maximum (Tmax) Concentration of LMP744 (NSC 706744) | 1.0 Hours |
| Treatment Assignment 2: LMP744 (MJ-III65 Hydrochloride) 12mg/m^2 | Dose Escalation & Dose Expansion Phase: Time to Maximum (Tmax) Concentration of LMP744 (NSC 706744) | 1.0 Hours |
| Treatment Assignment 3: LMP744 (MJ-III65 Hydrochloride) 24mg/m^2 | Dose Escalation & Dose Expansion Phase: Time to Maximum (Tmax) Concentration of LMP744 (NSC 706744) | 1.1 Hours |
| Treatment Assignment 4: LMP744 (MJ-III65 Hydrochloride) 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Time to Maximum (Tmax) Concentration of LMP744 (NSC 706744) | 1.0 Hours |
| Treatment Assignment 5: LMP744 (MJ-III65 Hydrochloride) 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Time to Maximum (Tmax) Concentration of LMP744 (NSC 706744) | 1.0 Hours |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Time to Maximum (Tmax) Concentration of LMP744 (NSC 706744) | 1.0 Hours |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Time to Maximum (Tmax) Concentration of LMP744 (NSC 706744) | 1.0 Hours |
| Trmt Assign. 6:LMP744 190mg/m^2 Foll. by Trmt Assign. 5: 96mg/m^2 Foll. by Trmt Assign. 4: 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Time to Maximum (Tmax) Concentration of LMP744 (NSC 706744) | 1.0 Hours |
| Treatment Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 | Dose Escalation & Dose Expansion Phase: Time to Maximum (Tmax) Concentration of LMP744 (NSC 706744) | 1.0 Hours |
| Trmt Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 Followed by Trmt Assign. 6: 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Time to Maximum (Tmax) Concentration of LMP744 (NSC 706744) | 1.0 Hours |
Other Pre-specified
Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level
Toxicity was assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A DLT is Grade ≥3 non-hematologic toxicity except Grade 3 fatigue lasting ≤ 7 days. Grade 4 hematological toxicity if it meets the following criteria: Lymphopenia (any grade) will not be considered dose limiting for all participants; Anemia: Grade 4 anemia will be considered dose limiting. Any neurotoxicity Grade ≥2 that is not reversible to a Grade ≤1 within 2 weeks will be considered dose limiting. Any non-hematologic Grade 2 toxicity that does not resolve to Grade ≤1 or baseline within 14 days despite adequate treatment, except for alopecia. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.
Time frame: Cycle 1 (28 days)
Population: A total of 35/36 participants were analyzed: 35/36 participants who enrolled received at least 1 dose of LMP744 (NSC 706744) and were evaluable for toxicity.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 5 DLT - Death | 0 toxicities |
| All Participants | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 3 DLT - Anemia | 0 toxicities |
| All Participants | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 3 DLT - Hypokalemia | 0 toxicities |
| All Participants | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 2 DLT - Weight loss | 0 toxicities |
| Treatment Assignment 2: LMP744 (MJ-III65 Hydrochloride) 12mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 2 DLT - Weight loss | 0 toxicities |
| Treatment Assignment 2: LMP744 (MJ-III65 Hydrochloride) 12mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 5 DLT - Death | 0 toxicities |
| Treatment Assignment 2: LMP744 (MJ-III65 Hydrochloride) 12mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 3 DLT - Anemia | 0 toxicities |
| Treatment Assignment 2: LMP744 (MJ-III65 Hydrochloride) 12mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 3 DLT - Hypokalemia | 0 toxicities |
| Treatment Assignment 3: LMP744 (MJ-III65 Hydrochloride) 24mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 3 DLT - Hypokalemia | 0 toxicities |
| Treatment Assignment 3: LMP744 (MJ-III65 Hydrochloride) 24mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 2 DLT - Weight loss | 0 toxicities |
| Treatment Assignment 3: LMP744 (MJ-III65 Hydrochloride) 24mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 3 DLT - Anemia | 0 toxicities |
| Treatment Assignment 3: LMP744 (MJ-III65 Hydrochloride) 24mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 5 DLT - Death | 0 toxicities |
| Treatment Assignment 4: LMP744 (MJ-III65 Hydrochloride) 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 3 DLT - Hypokalemia | 0 toxicities |
| Treatment Assignment 4: LMP744 (MJ-III65 Hydrochloride) 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 5 DLT - Death | 0 toxicities |
| Treatment Assignment 4: LMP744 (MJ-III65 Hydrochloride) 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 2 DLT - Weight loss | 0 toxicities |
| Treatment Assignment 4: LMP744 (MJ-III65 Hydrochloride) 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 3 DLT - Anemia | 0 toxicities |
| Treatment Assignment 5: LMP744 (MJ-III65 Hydrochloride) 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 3 DLT - Hypokalemia | 0 toxicities |
| Treatment Assignment 5: LMP744 (MJ-III65 Hydrochloride) 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 5 DLT - Death | 0 toxicities |
| Treatment Assignment 5: LMP744 (MJ-III65 Hydrochloride) 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 3 DLT - Anemia | 0 toxicities |
| Treatment Assignment 5: LMP744 (MJ-III65 Hydrochloride) 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 2 DLT - Weight loss | 0 toxicities |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 3 DLT - Anemia | 0 toxicities |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 5 DLT - Death | 0 toxicities |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 2 DLT - Weight loss | 1 toxicities |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 3 DLT - Hypokalemia | 1 toxicities |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 5 DLT - Death | 0 toxicities |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 3 DLT - Anemia | 1 toxicities |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 2 DLT - Weight loss | 0 toxicities |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 3 DLT - Hypokalemia | 0 toxicities |
| Trmt Assign. 6:LMP744 190mg/m^2 Foll. by Trmt Assign. 5: 96mg/m^2 Foll. by Trmt Assign. 4: 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 3 DLT - Hypokalemia | 0 toxicities |
| Trmt Assign. 6:LMP744 190mg/m^2 Foll. by Trmt Assign. 5: 96mg/m^2 Foll. by Trmt Assign. 4: 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 2 DLT - Weight loss | 0 toxicities |
| Trmt Assign. 6:LMP744 190mg/m^2 Foll. by Trmt Assign. 5: 96mg/m^2 Foll. by Trmt Assign. 4: 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 3 DLT - Anemia | 0 toxicities |
| Trmt Assign. 6:LMP744 190mg/m^2 Foll. by Trmt Assign. 5: 96mg/m^2 Foll. by Trmt Assign. 4: 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 5 DLT - Death | 0 toxicities |
| Treatment Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 3 DLT - Anemia | 0 toxicities |
| Treatment Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 3 DLT - Hypokalemia | 6 toxicities |
| Treatment Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 5 DLT - Death | 1 toxicities |
| Treatment Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 2 DLT - Weight loss | 0 toxicities |
| Trmt Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 Followed by Trmt Assign. 6: 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 2 DLT - Weight loss | 0 toxicities |
| Trmt Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 Followed by Trmt Assign. 6: 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 3 DLT - Hypokalemia | 0 toxicities |
| Trmt Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 Followed by Trmt Assign. 6: 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 5 DLT - Death | 0 toxicities |
| Trmt Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 Followed by Trmt Assign. 6: 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Grades 2, 3, 4 and/or 5 Dose-limiting Toxicities (DLT) by Dose Level | Grade 3 DLT - Anemia | 0 toxicities |
Other Pre-specified
Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT)
Toxicity was assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A DLT is Grade ≥3 non-hematologic toxicity except Grade 3 fatigue lasting ≤ 7 days. Grade 4 hematological toxicity if it meets the following criteria: Lymphopenia (any grade) will not be considered dose limiting for all participants; Anemia: Grade 4 anemia will be considered dose limiting. Any neurotoxicity Grade ≥2 that is not reversible to a Grade ≤1 within 2 weeks will be considered dose limiting. Any non-hematologic Grade 2 toxicity that does not resolve to Grade ≤1 or baseline within 14 days despite adequate treatment, except for alopecia. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.
Time frame: Cycle 1 (28 days)
Population: A total of 35/36 participants were analyzed: 35/36 participants who enrolled received at least 1 dose of LMP744 (NSC 706744) and were evaluable for toxicity.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Participants | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 3 DLT | 0 Participants |
| All Participants | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 4 DLT | 0 Participants |
| All Participants | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 2 DLT | 0 Participants |
| All Participants | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 5 DLT | 0 Participants |
| Treatment Assignment 2: LMP744 (MJ-III65 Hydrochloride) 12mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 2 DLT | 0 Participants |
| Treatment Assignment 2: LMP744 (MJ-III65 Hydrochloride) 12mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 5 DLT | 0 Participants |
| Treatment Assignment 2: LMP744 (MJ-III65 Hydrochloride) 12mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 4 DLT | 0 Participants |
| Treatment Assignment 2: LMP744 (MJ-III65 Hydrochloride) 12mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 3 DLT | 0 Participants |
| Treatment Assignment 3: LMP744 (MJ-III65 Hydrochloride) 24mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 3 DLT | 0 Participants |
| Treatment Assignment 3: LMP744 (MJ-III65 Hydrochloride) 24mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 4 DLT | 0 Participants |
| Treatment Assignment 3: LMP744 (MJ-III65 Hydrochloride) 24mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 5 DLT | 0 Participants |
| Treatment Assignment 3: LMP744 (MJ-III65 Hydrochloride) 24mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 2 DLT | 0 Participants |
| Treatment Assignment 4: LMP744 (MJ-III65 Hydrochloride) 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 4 DLT | 0 Participants |
| Treatment Assignment 4: LMP744 (MJ-III65 Hydrochloride) 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 5 DLT | 0 Participants |
| Treatment Assignment 4: LMP744 (MJ-III65 Hydrochloride) 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 2 DLT | 0 Participants |
| Treatment Assignment 4: LMP744 (MJ-III65 Hydrochloride) 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 3 DLT | 0 Participants |
| Treatment Assignment 5: LMP744 (MJ-III65 Hydrochloride) 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 3 DLT | 0 Participants |
| Treatment Assignment 5: LMP744 (MJ-III65 Hydrochloride) 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 5 DLT | 0 Participants |
| Treatment Assignment 5: LMP744 (MJ-III65 Hydrochloride) 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 2 DLT | 0 Participants |
| Treatment Assignment 5: LMP744 (MJ-III65 Hydrochloride) 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 4 DLT | 0 Participants |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 2 DLT | 0 Participants |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 3 DLT | 2 Participants |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 4 DLT | 1 Participants |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 5 DLT | 0 Participants |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 3 DLT | 1 Participants |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 2 DLT | 0 Participants |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 5 DLT | 0 Participants |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 4 DLT | 0 Participants |
| Trmt Assign. 6:LMP744 190mg/m^2 Foll. by Trmt Assign. 5: 96mg/m^2 Foll. by Trmt Assign. 4: 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 5 DLT | 0 Participants |
| Trmt Assign. 6:LMP744 190mg/m^2 Foll. by Trmt Assign. 5: 96mg/m^2 Foll. by Trmt Assign. 4: 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 4 DLT | 0 Participants |
| Trmt Assign. 6:LMP744 190mg/m^2 Foll. by Trmt Assign. 5: 96mg/m^2 Foll. by Trmt Assign. 4: 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 2 DLT | 0 Participants |
| Trmt Assign. 6:LMP744 190mg/m^2 Foll. by Trmt Assign. 5: 96mg/m^2 Foll. by Trmt Assign. 4: 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 3 DLT | 0 Participants |
| Treatment Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 5 DLT | 1 Participants |
| Treatment Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 4 DLT | 0 Participants |
| Treatment Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 3 DLT | 2 Participants |
| Treatment Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 2 DLT | 0 Participants |
| Trmt Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 Followed by Trmt Assign. 6: 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 5 DLT | 0 Participants |
| Trmt Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 Followed by Trmt Assign. 6: 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 2 DLT | 0 Participants |
| Trmt Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 Followed by Trmt Assign. 6: 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 3 DLT | 0 Participants |
| Trmt Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 Followed by Trmt Assign. 6: 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Presence and/or Absence of Grade 2 or Higher Dose Limiting Toxicity (DLT) | Grade 4 DLT | 0 Participants |
Other Pre-specified
Dose Escalation & Dose Expansion Phase: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
Here is the number of participants with serious and/or 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: From first drug administration through 30 days after the last dose of study drug is administered, an average of 12.9 months.
Population: A total of 35/36 participants were analyzed: 35/36 participants who enrolled received at least 1 dose of LMP744 (NSC 706744) and were evaluable for toxicity.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants | Dose Escalation & Dose Expansion Phase: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | 1 Participants |
| Treatment Assignment 2: LMP744 (MJ-III65 Hydrochloride) 12mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | 1 Participants |
| Treatment Assignment 3: LMP744 (MJ-III65 Hydrochloride) 24mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | 3 Participants |
| Treatment Assignment 4: LMP744 (MJ-III65 Hydrochloride) 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | 1 Participants |
| Treatment Assignment 5: LMP744 (MJ-III65 Hydrochloride) 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | 1 Participants |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | 14 Participants |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | 2 Participants |
| Trmt Assign. 6:LMP744 190mg/m^2 Foll. by Trmt Assign. 5: 96mg/m^2 Foll. by Trmt Assign. 4: 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | 1 Participants |
| Treatment Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | 10 Participants |
| Trmt Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 Followed by Trmt Assign. 6: 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | 1 Participants |
Other Pre-specified
Dose Escalation & Dose Expansion Phase: Percentage of Participants With Confirmed Objective Response Following Treatment With LMP744 (NSC 706744)
Antitumor activity is evaluated using the rate of confirmed objective responses according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria (i.e., at least a 30% decrease in the sum of the diameters of target lesions compared to the sum of baseline diameters).
Time frame: Tumor re-staging was performed every 2 cycles for the first year on study then every 3 cycles thereafter until a participant met criteria to be removed from the study; a median of 2 cycles completed and a full range of 0-31 cycles completed.
Population: A total of 35/36 participants were analyzed: tumor measurements from 35/36 participants who had radiologic imaging were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Dose Escalation & Dose Expansion Phase: Percentage of Participants With Confirmed Objective Response Following Treatment With LMP744 (NSC 706744) | 0 Percentage of participants |
| Treatment Assignment 2: LMP744 (MJ-III65 Hydrochloride) 12mg/m^2 | Dose Escalation & Dose Expansion Phase: Percentage of Participants With Confirmed Objective Response Following Treatment With LMP744 (NSC 706744) | 0 Percentage of participants |
| Treatment Assignment 3: LMP744 (MJ-III65 Hydrochloride) 24mg/m^2 | Dose Escalation & Dose Expansion Phase: Percentage of Participants With Confirmed Objective Response Following Treatment With LMP744 (NSC 706744) | 0 Percentage of participants |
| Treatment Assignment 4: LMP744 (MJ-III65 Hydrochloride) 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Percentage of Participants With Confirmed Objective Response Following Treatment With LMP744 (NSC 706744) | 0 Percentage of participants |
| Treatment Assignment 5: LMP744 (MJ-III65 Hydrochloride) 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Percentage of Participants With Confirmed Objective Response Following Treatment With LMP744 (NSC 706744) | 0 Percentage of participants |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Percentage of Participants With Confirmed Objective Response Following Treatment With LMP744 (NSC 706744) | 0 Percentage of participants |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Escalation & Dose Expansion Phase: Percentage of Participants With Confirmed Objective Response Following Treatment With LMP744 (NSC 706744) | 50 Percentage of participants |
| Trmt Assign. 6:LMP744 190mg/m^2 Foll. by Trmt Assign. 5: 96mg/m^2 Foll. by Trmt Assign. 4: 48mg/m^2 | Dose Escalation & Dose Expansion Phase: Percentage of Participants With Confirmed Objective Response Following Treatment With LMP744 (NSC 706744) | 0 Percentage of participants |
| Treatment Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 | Dose Escalation & Dose Expansion Phase: Percentage of Participants With Confirmed Objective Response Following Treatment With LMP744 (NSC 706744) | 0 Percentage of participants |
| Trmt Assignment 7: LMP744 (MJ-III65 Hydrochloride) 260mg/m^2 Followed by Trmt Assign. 6: 190mg/m^2 | Dose Escalation & Dose Expansion Phase: Percentage of Participants With Confirmed Objective Response Following Treatment With LMP744 (NSC 706744) | 0 Percentage of participants |
Other Pre-specified
Dose Expansion Phase: Percent Change of Nuclei With ≥19 Topoisomerase 1 Cleavage Complex (Top1cc) Foci in Paired Biopsies
Percent of nuclei with ≥19 Top1cc foci in paired pre-treatment and on-treatment tumor biopsies were quantified in response to treatment with LMP744 (NSC 706744)
Time frame: Baseline (pre-treatment) and Cycle 1 Day 1 at 1-4 hours after the end of the LMP744 (NSC 706744) infusion.
Population: A total of 6/36 participants were analyzed: paired biopsy samples from 6 participants in the expansion phase were collected for pharmacodynamic analyses; one biopsy pair was not quantifiable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Expansion Phase: Percent Change of Nuclei With ≥19 Topoisomerase 1 Cleavage Complex (Top1cc) Foci in Paired Biopsies | Pre-Treatment | 15.4 Percent change | Standard Deviation 14 |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Expansion Phase: Percent Change of Nuclei With ≥19 Topoisomerase 1 Cleavage Complex (Top1cc) Foci in Paired Biopsies | On-Treatment (After end of infusion) | 13.3 Percent change | Standard Deviation 7.6 |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Expansion Phase: Percent Change of Nuclei With ≥19 Topoisomerase 1 Cleavage Complex (Top1cc) Foci in Paired Biopsies | Pre-Treatment | 7.6 Percent change | Standard Deviation 0.6 |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Expansion Phase: Percent Change of Nuclei With ≥19 Topoisomerase 1 Cleavage Complex (Top1cc) Foci in Paired Biopsies | On-Treatment (After end of infusion) | 3.2 Percent change | Standard Deviation 4.4 |
Other Pre-specified
Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Phosphorylated Form of Gamma H2A Histone Family Member X (γH2AX) Staining
Levels of γH2AX in paired pre-treatment and on-treatment tumor biopsies were quantified in response to treatment with LMP744 (NSC 706744)
Time frame: Baseline (pre-treatment) and Cycle 1 Day 1 at 1-4 hours after the end of the LMP744 (NSC 706744) infusion.
Population: A total of 6/36 participants were analyzed: paired biopsy samples from 6 participants in the expansion phase were collected for pharmacodynamic analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Phosphorylated Form of Gamma H2A Histone Family Member X (γH2AX) Staining | Pre-Treatment | 0.5 Percent of Nuclear Positive Area (NAP) | Standard Deviation 0.1 |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Phosphorylated Form of Gamma H2A Histone Family Member X (γH2AX) Staining | On-Treatment (after end of infusion) | 0.6 Percent of Nuclear Positive Area (NAP) | Standard Deviation 0.3 |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Phosphorylated Form of Gamma H2A Histone Family Member X (γH2AX) Staining | Pre-Treatment | 0.4 Percent of Nuclear Positive Area (NAP) | Standard Deviation 0 |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Phosphorylated Form of Gamma H2A Histone Family Member X (γH2AX) Staining | On-Treatment (after end of infusion) | 5.5 Percent of Nuclear Positive Area (NAP) | Standard Deviation 7 |
Other Pre-specified
Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Phosphorylated Krüppel Associated Box (KRAB) Domain-Associated Protein 1 (pKap1) Staining
Levels of pKap1 in paired pre-treatment and on-treatment tumor biopsies were quantified in response to treatment with LMP744 (NSC 706744)
Time frame: Baseline (pre-treatment) and Cycle 1 Day 1 at 1-4 hours after the end of the LMP744 (NSC 706744) infusion.
Population: A total of 6/36 participants were analyzed: paired biopsy samples from 6 participants in the expansion phase were collected for pharmacodynamic analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Phosphorylated Krüppel Associated Box (KRAB) Domain-Associated Protein 1 (pKap1) Staining | Pre-Treatment | 0.3 Percent of Nuclear Positive Area (NAP) | Standard Deviation 0.1 |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Phosphorylated Krüppel Associated Box (KRAB) Domain-Associated Protein 1 (pKap1) Staining | On-Treatment (after end of infusion) | 0.2 Percent of Nuclear Positive Area (NAP) | Standard Deviation 0.1 |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Phosphorylated Krüppel Associated Box (KRAB) Domain-Associated Protein 1 (pKap1) Staining | Pre-Treatment | 0.5 Percent of Nuclear Positive Area (NAP) | — |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Phosphorylated Krüppel Associated Box (KRAB) Domain-Associated Protein 1 (pKap1) Staining | On-Treatment (after end of infusion) | 0.1 Percent of Nuclear Positive Area (NAP) | Standard Deviation 0.2 |
Other Pre-specified
Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Phosphorylated Nibrin (pNbs1) Staining
Levels of pNbs1 in paired pre-treatment and on-treatment tumor biopsies were quantified in response to treatment with LMP744 (NSC 706744)
Time frame: Baseline (pre-treatment) and Cycle 1 Day 1 at 1-4 hours after the end of the LMP744 (NSC 706744) infusion.
Population: A total of 6/36 participants were analyzed: paired biopsy samples from 6 participants in the expansion phase were collected for pharmacodynamic analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Phosphorylated Nibrin (pNbs1) Staining | Pre-Treatment | 1.2 Percent of Nuclear Positive Area (NAP) | Standard Deviation 0.7 |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Phosphorylated Nibrin (pNbs1) Staining | On-Treatment (after end of infusion) | 1.5 Percent of Nuclear Positive Area (NAP) | Standard Deviation 1 |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Phosphorylated Nibrin (pNbs1) Staining | Pre-Treatment | 0.2 Percent of Nuclear Positive Area (NAP) | Standard Deviation 0.1 |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Phosphorylated Nibrin (pNbs1) Staining | On-Treatment (after end of infusion) | 0.4 Percent of Nuclear Positive Area (NAP) | Standard Deviation 0.2 |
Other Pre-specified
Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for RAD Recombinase (Rad51) Staining
Levels of Rad51 in paired pre-treatment and on-treatment tumor biopsies were quantified in response to treatment with LMP744 (NSC 706744)
Time frame: Baseline (pre-treatment) and Cycle 1 Day 1 at 1-4 hours after the end of the LMP744 (NSC 706744) infusion.
Population: A total of 6/36 participants were analyzed: paired biopsy samples from 6 participants in the expansion phase were collected for pharmacodynamic analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for RAD Recombinase (Rad51) Staining | On-Treatment (after end of infusion) | 4.3 Percent of Nuclear Positive Area (NAP) | Standard Deviation 2.6 |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for RAD Recombinase (Rad51) Staining | Pre-Treatment | 0.2 Percent of Nuclear Positive Area (NAP) | Standard Deviation 0.2 |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for RAD Recombinase (Rad51) Staining | Pre-Treatment | 0.3 Percent of Nuclear Positive Area (NAP) | Standard Deviation 0.1 |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for RAD Recombinase (Rad51) Staining | On-Treatment (after end of infusion) | 3.4 Percent of Nuclear Positive Area (NAP) | Standard Deviation 3.9 |
Other Pre-specified
Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Topoisomerase I (Top1) Staining
Levels of Top1 in paired pre-treatment and on-treatment tumor biopsies were quantified in response to treatment with LMP744 (NSC 706744)
Time frame: Baseline (pre-treatment) and Cycle 1 Day 1 at 1-4 hours after the end of the LMP744 (NSC 706744) infusion.
Population: A total of 6/36 participants were analyzed: paired biopsy samples from 6 participants in the expansion phase were collected for pharmacodynamic analyses; one biopsy pair was not quantifiable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Topoisomerase I (Top1) Staining | Pre-Treatment | 7.0 Percent of Nuclear Positive Area (NAP) | Standard Deviation 3.7 |
| Treatment Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 | Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Topoisomerase I (Top1) Staining | On-Treatment (after end of infusion) | 6.4 Percent of Nuclear Positive Area (NAP) | Standard Deviation 4.1 |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Topoisomerase I (Top1) Staining | Pre-Treatment | 2.2 Percent of Nuclear Positive Area (NAP) | Standard Deviation 0.1 |
| Trmt Assignment 6: LMP744 (MJ-III65 Hydrochloride) 190mg/m^2 Followed by Trmt Assign. 5: 96mg/m^2 | Dose Expansion Phase: Percent of Nuclear Area Positive (NAP) for Topoisomerase I (Top1) Staining | On-Treatment (after end of infusion) | 1.3 Percent of Nuclear Positive Area (NAP) | Standard Deviation 1.3 |