Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

All Drugs and Chemicals

Anti-Infective Agents

Peposertib

Trichostatin A

Protein Kinase Inhibitors

Enzyme Inhibitors

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.

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.

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.

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.

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.

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.

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.

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.

MSC2490484A (M3814)

Medical Responsible

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.

Clinical Phase I Study Investigating MSC2490484A, an Inhibitor of a DNA-dependent Protein Kinase, in Advanced Solid Tumors or Chronic Lymphocytic Leukemia

A Multicenter, Open-Label, Dose-Escalating Phase I Trial of the DNA-PK Inhibitor MSC2490484A in Subjects With Advanced Solid Tumors or Chronic Lymphocytic Leukemia

Merck KGaA, Darmstadt, Germany

Antineoplastic Agents

Avelumab

Antineoplastic Agents, Immunological

Participants will receive M3814 twice daily (BID) continuously starting from Day 1 until progressive disease (PD) or unacceptable toxicity.

M3814

Participants will receive M3814 concomitantly with RT once (QD) daily starting Day 1 for 5 days per week for 2 weeks in total.

Participants will receive avelumab once every 2 weeks (Q2W) starting from Day 1 until PD or unacceptable toxicity.

Participants will receive radiotherapy at the dose of 3 grays (Gy) per day starting Day 1 for 5 days per week for 2 weeks.

Radiotherapy

The main purpose of the study is to evaluate a safe, tolerable recommended Phase II dose (RP2D) and/or the maximum tolerated dose (MTD) of M3814 when given in combination with avelumab with and without radiotherapy in participants with selected advanced solid tumors.

Study of Avelumab-M3814 Combinations

A Multicenter, Open-Label, Dose Escalation Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of the DNA-PK Inhibitor M3814 in Combination With Avelumab With and Without Palliative Radiotherapy in Participants With Selected Advanced Solid Tumors

Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany, will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://www.merckgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html

Number of participants with clinically significant abnormalities will be reported.

EMD Serono Research & Development Institute, Inc.

Cisplatin

Subjects will receive MSC2490484A tablet once daily up to 10 times, for two consecutive weeks in concomitance with fractionated radiotherapy (RT) (5 fractions /week).

Subjects will receive MSC2490484A capsule once daily up to 35 times, for 7 consecutive weeks in concomitance with fractionated RT and Cisplatin (5 fractions/week).

Subjects will receive MSC2490484A tablet once daily up to 35 times in concomitance with fractionated RT (5 fractions /week).

Subjects will receive MSC2490484A tablet once daily up to 35 times in concomitance with fractionated RT (5 fractions /week) and cisplatin.

Ancillary Clinical proof-of-principle (cPOP) study, subjects will receive first dose of RT on Day 1, and will receive MSC2490484A capsule or Tablet formulation within 1.5 hour before the second dose of RT on Day 2.

Phase Ia: Subjects will receive a starting dose of 100 milligram (mg) or 50 mg of MSC2490484A as Capsule or tablet orally once daily 1.5 hours prior each RT.

Phase Ia: Subjects will receive fractionated palliative RT (3 Gray \[Gy\] \* 10 in Arm A and 2 Gy \* 33 to 35, 5 fractions per week \[F/W\]) in Arm B.

Fractionated RT

Cisplatin will be given twice at a dose of 100 milligram per square meter (mg/m\^2) or weekly at a dose of 40 (mg/m\^2).

Phase Ib: Subjects will receive the assigned dose of MSC2490484A once daily orally.

Ancillary cPoP Study: Subjects will receive a single oral MSC2490484A capsule on Day 2, 1.5 hours before the start of RT.

Phase Ib: Subjects will receive fractionated RT (2 Gy x 33, 5 F/W).

Ancillary cPoP study: Subjects will receive a single high dose of RT (10-25 Gy) capsule on Day 1 given on Lesion 1 and a single high dose of RT (10-25 Gy) on Day 2 given on Lesion 2.

MSC2490484A or M3814 is an investigational drug that is being evaluated for the treatment of subjects with locally advanced tumors. The main purposes of this study are to determine the safety, the tolerability and the efficacy of MSC2490484A in combination with radiotherapy and in combination with chemoradiotherapy (Radiotherapy + cisplatin).

Phase 1 Trial of MSC2490484A, an Inhibitor of a DNA-dependent Protein Kinase, in Combination With Radiotherapy

An Open Label, Phase Ia/Ib Trial of the DNA-PK Inhibitor MSC2490484A in Combination With Radiotherapy in Patients With Advanced Solid Tumors

DLT: any Grade \>= 3 nonhematologic AE or Grade \>= 4 hematologic AE according to NCI-CTCAE version 4.03, related to any of study treatments \& occurs during DLT period of 5 weeks(Phase Ia, Arm A)/12 weeks (Phase Ia, Arm B \& Phase Ib. In addition, following are considered DLTs: Grade 3 thrombocytopenia with medically concerning bleeding, Febrile neutropenia, Any toxicity or study treatment-related TEAE ADRs that, in opinion of SMC, is of potential clinical significance, Any toxicity related to study treatments that causes subject to receive less than 80% of planned radiotherapy (RT) dose, Any toxicity related to study treatments leading to an interruption of RT longer than 1 week in Arm B \& Evidence of study treatment related hepatocellular injury for more than 3 days.

DLT is defined as any of the following toxicities assessed as at least possibly related to MSC2490484A by the Investigator and/or the Sponsor up to 12 weeks after irst dose of MSC2490484A in combination with standard chemoradiotherapy (CRT) (with cisplatin): A treatment-emergent adverse event (TEAE) of potential clinical significance; evidence of possible treatment-related hepatocellular injury for more than 3 days as defined in the protocol; any Grade greater than or equal to (\>=) 3 toxicity, but excluding the conditions mentioned in the protocol; any Grade 4 neutropenia of greater than (\>)5 days duration or Grade \>=3 febrile neutropenia; any Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding; any toxicity related to trial drug that causes the subject to receive less than 80 percent (%) of planned MSC2490484A and/or RT dose and/or CRT.

An Adverse Event (AE) is defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A Serious AE (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.

Best overall response is defined as occurrence of complete response (CR) or partial response (PR) based on the Investigator's assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 confirmed at a repeat assessment performed no less than 28 days after the criteria for response are first met. Complete response (CR) is defined as disappearance of all target and non-target lesions. Partial response (PR) is defined as at least 30% decrease in the sum of the diameters of target or non-target lesions taking as reference the baseline sum diameters, with no evidence of progressive disease (PD). PD is defined as at least 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on trial, or unequivocal progression of existing non-target lesions.

PFS time will be evaluated according to RECIST Version 1.1.

Overall Survival (OS) Time will be evaluated according to RECIST Version 1.1.

Respiratory Tract (Lung and Bronchial) Diseases

Small Cell Lung Carcinoma

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

Etoposide

Etoposide phosphate

Participants received M3814 100 milligram (mg) powder in capsule (PiC) orally once daily in combination with Etoposide 100 mg/m\^2 over a 60 minute intravenous infusion on Days 1-3 and Cisplatin 75 milligram per square meter (mg/m\^2) over a 60-minute intravenous infusion on Day 1 for 6 cycles with each cycle lasting 3 weeks (21 days) until progressive disease (PD).

Participants received M3814 100 mg hot melt extrusion (HME) tablet orally 5 days prior to Day 1 and M3814 100 mg PiC, orally once daily from Day 1 in combination with Etoposide 100 mg/m\^2 over a 60 minute intravenous infusion on Days 1-3 and Cisplatin 75 mg/m\^2 over a 60-minute intravenous infusion on Day 1 for 6 cycles with each cycle lasting 3 weeks (21 days) until PD.

Participants received M3814 PiC or hot melt extrusion (HME) tablet orally once daily in combination with etoposide (intravenously) and cisplatin for 6 cycles with each cycle lasting 3 weeks (21 days).

Cisplatin 75 milligram per square meter (mg/m\^2) was administered over a 60-minute intravenous infusion on Day 1.

Etoposide 100 mg/m\^2 over a 60 minute IV infusion on Days 1-3 was administered for 6 cycles with each cycle lasting 3 weeks (21 days).

M3814 is an investigational drug under evaluation for treatment of lung cancer. The purpose of the study was to assess the Safety and Efficacy of M3814 in combination with chemotherapy with SCLC ED.

The study was intended to be a phase I/II trial, but the study never moved forward to Phase II due to recruitment challenges.

Phase Ib/II Study of M3814 With Etoposide and Cisplatin in Small Cell Lung Cancer (SCLC) Extensive Disease (ED)

A Multicenter Study With an Open Label Phase Ib Part Followed by a Randomized, Placebo-controlled, Double-blind, Phase II Part to Evaluate Efficacy, Safety, Tolerability, and PK of M3814 in Combination With Etoposide and Cisplatin in Subjects With Treatment-naïve Small Cell Lung Cancer (SCLC) Extensive Disease (ED)

PFS time will be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. The PFS time is defined as the duration from randomization to either first observation of progressive disease (PD) or occurrence of death due to any cause.

An Adverse Event (AE) is defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.

Subjects will be analyzed for vital signs (eg, body temperature, respiratory rate, heart rate, and blood pressure), laboratory parameters and 12-lead ECG recorded at baseline and after administration of M3814. Number of subjects with abnormal values for laboratory values, vital signs and electrocardiograms (ECGs) will be reported.

The Objective Response Rate (ORR) is defined as the percentage of subjects whose Best objective response (BOR) is either complete response (CR) or partial response (PR). The ORR will be derived from the BOR according to response evaluation criteria in solid tumors (RECIST) v1.1 as assessed by the Investigator.

The DoR applies only to subjects whose BOR is either CR or PR. The duration is measured from the first documented response (CR or PR, whichever is first recorded) until the first assessment of Progressive Disease (PD).The DoR will be derived from the BOR according to RECIST v1.1 as assessed by the Investigator.

Percentage of subjects with disease control as assessed by best overall response of either CR, PR or Stable Disease (SD) will be reported.

The PFS time is defined as the duration from randomization to either first observation of progressive disease (PD) or occurrence of death due to any cause. The PFS will be derived according to RECIST v1.1 as assessed by the Investigator.

The OS time is defined as the date from randomization to death due to any cause.

The Objective Response Rate (ORR) is defined as the proportion of subjects whose Best objective response (BOR) is either complete response (CR) or partial response (PR). The ORR will be derived from the BOR according to response evaluation criteria in solid tumors (RECIST) Version 1.1 as assessed by the Investigator.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Clinical Phase I Study Investigating MSC2490484A, an Inhibitor of a DNA-dependent Protein Kinase, in Advanced Solid Tumors or Chronic Lymphocytic Leukemia	NCT02316197	Advanced Solid ... Chronic Lymphoc...	MSC2490484A (M3...	18 Years -	Merck KGaA, Darmstadt, Germany
Study of Avelumab-M3814 Combinations	NCT03724890	Oncology Solid Tumors	M3814 M3814 Avelumab Radiotherapy	18 Years -	EMD Serono
Phase 1 Trial of MSC2490484A, an Inhibitor of a DNA-dependent Protein Kinase, in Combination With Radiotherapy	NCT02516813	Advanced Solid ...	MSC2490484A (M3... Fractionated RT Cisplatin MSC2490484A (M3... MSC2490484A (M3... Fractionated RT Fractionated RT	18 Years -	EMD Serono
Phase 1 Trial of MSC2490484A, an Inhibitor of a DNA-dependent Protein Kinase, in Combination With Radiotherapy	NCT02516813	Advanced Solid ...	MSC2490484A (M3... Fractionated RT Cisplatin MSC2490484A (M3... MSC2490484A (M3... Fractionated RT Fractionated RT	18 Years -	EMD Serono
Phase Ib/II Study of M3814 With Etoposide and Cisplatin in Small Cell Lung Cancer (SCLC) Extensive Disease (ED)	NCT03116971	Small Cell Lung...	M3814 Cisplatin Etoposide	18 Years -	EMD Serono

Spots Global Cancer Trial Database for m3814

Every month we try and update this database with for m3814 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for m3814

Every month we try and update this database with for m3814 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for m3814 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.