A Phase 1 interventional study of MSC2490484A (M3814) in Advanced Solid Tumors and Chronic Lymphocytic Leukemia, sponsored by Merck KGaA, Darmstadt, Germany. Completed at 7 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-04-28.
Sponsored by Merck KGaA, Darmstadt, Germany · Phase 1, Interventional, and Treatment
MSC2490484A is an investigational drug that is being evaluated for the treatment of subjects with advanced solid tumors or chronic lymphocytic leukemia (CLL) that likely differs from other cancers in how it repairs damaged DNA (genetic material). This is a first-in-man Phase I study, which means that it is the first time the study drug is being used in humans. The main purpose is to determine the highest dose that does not cause unacceptable side effects. The second is to determine the appropriate dose to use in future research for subjects with cancer. Othergoals of the study are to learn about the drug's safety and side effects, how it affects the tumor, and how the body processes the drug.
This is a Phase I, first-in-human, open-label, dose escalation, and dose expansion trial designed to explore the safety, tolerability, PK and PD profiles, and clinical activity of MSC2490484A administered daily as a single agent to subjects with advanced solid tumors or CLL likely to have alterations in DNA repair mechanisms.
Dose Escalation : Subjects will receive MSC2490484A continuously at the starting dose of 100 mg once daily. Sequential treatment cohorts will receive ascending doses of MSC2490484A once daily or twice daily (if determined to be appropriate by the Safety Monitoring Committee [SMC]) following a standard "3+3" design. The SMC will make dose escalation decisions based on review of available safety, tolerability, Pharmacokinetic (PK), and Pharmacodynamic (PD) data. Once the maximum tolerated dose (MTD) has been established, an Recommended Phase II Dose (RP2D) will be defined by the SMC, either at the MTD level or another dose level, depending on the available data on safety, efficacy, PK, and PD observed in the trial. The SMC may decide to stop dose escalation at any time during the trial.
Up to 12 subjects will be enrolled at the RP2D/Optimal biologic dose (OBD) to confirm safety and tolerability and explore the PK and PD profile of MSC2490484A.
Expansion cohorts: Once subjects have been evaluated at the RP2D, additional subjects will be enrolled into 2 or more expansion cohorts (20 evaluable subjects per expansion cohort) to evaluate clinical efficacy in tumors likely to have alterations in the DNA repair mechanism (eg, CLL and other tumor types). Subjects are evaluable for efficacy if they have received at least 1 dose of study drug and have radiographic baseline. Subjects who are not evaluable for efficacy will be replaced.
5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.
This study's enrollment of 31 is below the median of 38 across 4,247 interventional studies indexed under Leukemia.
Browse Leukemia studies →Merck KGaA, Darmstadt, Germany is the lead sponsor of 269 studies on the registry; none are open to participants now.
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Exclusion Criteria:
Participants received MSC2490484A capsules 100 milligram (mg) orally, once daily (QD) from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814.
Drug: MSC2490484A (M3814)
Participants received MSC2490484A capsules 200 mg orally, QD from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814.
Drug: MSC2490484A (M3814)
Participants received MSC2490484A capsules 150 mg orally, twice daily (BID) from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814.
Drug: MSC2490484A (M3814)
Participants received MSC2490484A capsules 200 mg orally, BID from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814.
Drug: MSC2490484A (M3814)
Participants received MSC2490484A capsules 300 mg orally, BID from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814.
Drug: MSC2490484A (M3814)
Participants received MSC2490484A capsules 400 mg orally, BID from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814.
Drug: MSC2490484A (M3814)
Participants received MSC2490484A capsules 400 mg recommended Phase II dose (RP2D) orally, BID from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814.
Drug: MSC2490484A (M3814)
Participants received MSC2490484A capsules at escalated dose from 100 mg to 400 mg orally from Day 1 to Day 21 of each treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent, and/or occurrence of any criterion for withdrawal from study or M3814.
Also known as: M3814, Peposertib
Number of Dose limiting toxicities (DLTs) occurring in Cycle 1
Time frame: up to Day 21 of Cycle 1
Maximum Observed Plasma Concentration (Cmax)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Time to Maximum Observed Plasma Concentration (tmax)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Minimum Observed Plasma Concentration During a Complete Dosing Interval (Cmin)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Average Observed Plasma Concentration (Cavg)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Fluctuation Index
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Area Under the Concentration-Time Curve From Time Zero To 24 Hours (AUC0-24)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Area Under the Concentration-Time Curve From Time Zero To 12 Hours (AUC0-12)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Area Under the Concentration-Time Curve From Time Zero To the Time of Last Quantifiable Concentration (AUC0-t)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Area Under the Concentration-Time Curve From Time Zero Extrapolated To Infinity (AUC0-inf)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Area Under the Concentration-Time Curve From Time Zero to Time tau at Steady State (AUCtau)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Apparent Terminal Half-Life (t1/2)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Terminal Rate Constant (λz)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Oral Clearance (CL/f)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Apparent Volume of Distribution During Terminal Phase (Vz/f)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Apparent Volume of Distribution at Steady State (Vss/f)
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Accumulation Ratio for Area Under The Concentration-Time Curve (Racc[AUC])
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Accumulation Ratio for Maximum Concentration (Racc[Cmax])
Time frame: Day 1 of Cycle 1 (cycle length = 21 days)
Best overall response rate
Time frame: Time from first dose to disease progression or death, whichever occurs first, assessed until 12 weeks after last patient treated
Clinical benefit rate defined as the proportion of subjects with CR, PR, or stable disease at Week 12
Time frame: Week 12
Progression-free survival time (PFS)
Time frame: Time from first dose to disease progression or death, whichever occurs first, assessed until 12 weeks after last patient treated
This study is completed, as verified in Apr 2020. You cannot join it, but the record below documents what was studied.
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Merck KGaA, Darmstadt, Germany