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OncologyPhase 1NCT03724890

Study of Avelumab-M3814 Combinations

A Phase 1 study testing M3814, Avelumab and Radiotherapy in people with Oncology and Solid Tumors, run by EMD Serono Research & Development Institute, Inc. at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The main purpose of the study was 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Oncology, Solid Tumors
What is being tested?
M3814, Avelumab and Radiotherapy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
57 participants
Where
8 sitesUnited States
Study dates
27 Nov 2018to 17 Aug 2022
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Part A and Part FE (M3814 + avelumab): Participants had histologically or cytologically proven advanced or metastatic solid tumors for which no standard therapy exists, standard therapy has failed, or participants are intolerant to or have rejected established therapy known to provide clinical benefit for their condition
  • Part B (M3814 + Radiotherapy [RT] + avelumab): histologically or cytologically proven advanced or metastatic solid tumors for which no standard therapy exists, standard therapy has failed, or participants are intolerant to or have rejected established therapy known to provide benefit for their condition and are amenable to receive RT
  • Part A, B and FE: Measurable or evaluable disease according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1)
  • Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1 at study entry
  • Part A, B and FE: Female participants of childbearing potential should be willing to use a highly effective contraceptive method
  • Part A, B and FE: Male participants should agree to refrain from donating sperm plus, either: abstain from any activity that allows for exposure to ejaculate
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  • Use an adequate method of contraception starting with the first dose of study therapy through 90 days after the last dose of study therapy
  • Part A, B and FE: Be willing to provide informed consent for the trial
  • Other protocol defined inclusion criteria could apply

Who cannot join

  • Participants who had received prior chemotherapy, hormonal anticancer therapy with the exception of luteinizing hormone-releasing hormone analogs, biologic therapy, or any other anticancer therapy within 28 days of the first dose of study treatments (6 weeks for nitrosoureas or mitomycin C)
  • Participants who had undergone major surgery for any reason, except diagnostic biopsy, within 4 weeks of the study intervention and/or has not fully recovered from the surgery within 4 weeks of the study intervention
  • Participants with evidence of active or history of autoimmune disease that might deteriorate when receiving an immune-stimulatory agent
  • Participants with brain metastases, except those meeting the following criteria: a) brain metastases that have been treated locally and are clinically stable for greater than or equal to (>=) 4 weeks prior to randomization b) no ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable) c) participants must be either off steroids or on a stable or decreasing dose of less than (<) 10 milligrams (mg) daily prednisone (or equivalent)
  • Participants with severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year), psychiatric or substance abuse disorders; or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study intervention administration or may interfere with the interpretation of study results
  • Participants requiring systemic immunosuppressive agents (such as steroids) for any reason who cannot be tapered off these drugs before start of study intervention, with the following exceptions: a) participants with adrenal insufficiency, may continue corticosteroids at physiologic replacement dose, equivalent to less than or equal to (<=) 10 mg prednisone daily b) participants requiring steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intra-ocular, or inhalation) is permitted c) participants with previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon planned to be completed in 14 days, or that the dose after 14 days will be equivalent to <= 10 mg prednisone daily
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  • Participants with a history of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome, Hepatitis B virus or Hepatitis C and with history of infection must have a polymerase chain reaction (PCR) documentation that infection is cleared
  • Participants who had received a live vaccine within 30 days prior to the first dose of trial treatment
  • Participants with known prior severe hypersensitivity to any of the investigational products or any component in its formulations
  • Participants with evidence of additional malignancy within the last 5 years unless a complete remission without further recurrence was achieved at least 2 years prior to study entry and participants were deemed to have been cured with no additional therapy required or anticipated to be required. Participants with treated nonmelanoma skin cancers, carcinoma in situ of skin, bladder, cervix, colon/rectum, breast, or prostate may participate
  • Participants pretreated with immunotherapy who have, any history of dose limiting toxicities (DLTs) with prior immunotherapy agents, including Grade 3/4 immune-related adverse events (irAEs); irreversible irAEs; Grade greater than or equals to (>=) 3 irAEs that did not respond to steroid rescue; or neurologic irAE with significant clinical sequelae
  • Participants with irAE requiring hormone replacement therapy (e.g., thyroxine, insulin, or physiologic dose of corticosteroid replacement therapy for adrenal or pituitary insufficiency) may participate as long as the endocrinopathy is well controlled and the participant is not otherwise symptomatic from hormone insufficiency
  • Physiologic corticosteroid dose is defined as <= 10 mg daily of prednisone or equivalent
  • for Part B only:
  • Participants who had confirmed esophagitis and in whom radiation planning target volume will include any portion of the esophagus, the participant is not eligible unless an esophageal endoscopy rules out the presence of esophagitis
  • Participants in whom more than 10 percent (%) of the total esophagus volume might receive more than 15 gray (Gy) (50% of the prescribed radiotherapy [RT] dose)
  • Participants who have had previous radiotherapy to the same region as intended to be irradiated in this study within the past 12 months
  • Participants who had had extensive previous radiotherapy on >= 30% of bone marrow reserve or prior bone marrow/stem cell transplantation within 5 years before study start
  • If participant hepatic metastatic lesion is selected to be irradiated: - the non-tumor liver volume < 700 milli liters (mL); - Child-Pugh score >= 8
  • Other protocol defined exclusion criteria could apply

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • The University of Chicago Medical Center

    Chicago, Illinois, 60637

  • UC Health Clinical Trials Office (10702)

    Cincinnati, Ohio, 45267-0502

  • Greenville Hospital System University Medical Center (ITOR)

    Greenville, South Carolina, 29605

  • Mount Sinai - PRIME (10707)

    Lake Success, New York, 11041

  • Vanderbilt-Ingram Cancer Center (8867)

    Nashville, Tennessee, 37212

  • University of Oklahoma Health Sciences Center - Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73104

  • University of Pittsburgh Medical Center Health System

    Pittsburgh, Pennsylvania, 15213

  • H. Lee Moffitt Cancer Center and Research Institute, Inc

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: 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

The main purpose of the study was 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.

Being tested
M3814, Avelumab, Radiotherapy
Keywords
Palliative Radiotherapy, Advanced solid tumors, M3814, Avelumab
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • M3814Drug

    Also called Peposertib, MSC2490484A

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

  • M3814Drug

    Also called Peposertib, MSC2490484A

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

  • AvelumabDrug

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

  • RadiotherapyRadiation

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

Study groups in NCT03724890
Study groupRoleWhat they receive
Part A: M3814 + AvelumabExperimentalNot described
Receives: Drug: M3814; Drug: Avelumab
Part B: M3814 + Avelumab + Radiotherapy (RT)ExperimentalNot described
Receives: Drug: M3814; Drug: Avelumab; Radiation: Radiotherapy
Part FE: M3814 + Avelumab (fasted/fed state)ExperimentalNot described
Receives: Drug: M3814; Drug: Avelumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part A: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) Assessed Using National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Version 5.0

    A DLT was defined as any Grade more than or equal to >= 3 nonhematologic Adverse Event(AE) or any Grade>= 4 hematologic,, occurring during the DLT period that is related to any of the study interventions. In addition, a DLT is considered: Grade 3 thrombocytopenia with medically concerning bleeding, Any febrile neutropenia. A study intervention-related Treatment emergent Adverse Event(TEAE) is of potential clinical significance such that further dose escalation would expose participants to unacceptable risk. Any toxicity related to study intervention that causes the participant to receive less than 80% of M3814 during DLT period, evidence of study treatment-related hepatocellular injury for more than 3 days, such as> 5-fold elevations above the Upper Limits of Normal (ULN) of Alanine Aminotransferase (ALT) or Aspartate Aminotransferase(AST) with or without elevation of serum total bilirubin to > 2 × ULN. Number of Participants with DLT Grade >= 3 were reported.

    Measured: Day 1 up to Day 21

  2. Part B: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) Assessed Using National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Version 5.0

    A DLT was defined as any Grade more than or equal to >= 3 nonhematologic Adverse Event(AE) or any Grade>= 4 hematologic,, occurring during the DLT period that is related to any of the study interventions. In addition, a DLT is considered: Grade 3 thrombocytopenia with medically concerning bleeding, Any febrile neutropenia. A study intervention-related Treatment emergent Adverse Event(TEAE) is of potential clinical significance such that further dose escalation would expose participants to unacceptable risk. Any toxicity related to study intervention that causes the participant to receive less than 80% of M3814 during DLT period, evidence of study treatment-related hepatocellular injury for more than 3 days, such as> 5-fold elevations above the Upper Limits of Normal (ULN) of Alanine Aminotransferase (ALT) or Aspartate Aminotransferase(AST) with or without elevation of serum total bilirubin to > 2 × ULN. Number of Participants with DLT Grade >= 3 were reported.

    Measured: Day 1 up to Day 28

  3. Part Food Effect (FE): Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to 6 Hour (AUC0-6hour) of M3814

    Area under the plasma concentration versus time curve from time zero to 6 hours post dosing for M3814 was reported.

    Measured: Pre-dose, 1, 2, 4 and 6 hours post-dose on Day 1; Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Day 15; Pre-dose, 2, 4 and 6 hours post-dose on Day 22

  4. Part FE: Maximum Observed Plasma Concentration (Cmax) of M3814

    Cmax was obtained directly from the concentration versus time curve.

    Measured: Pre-dose, 1, 2, 4 and 6 hours post-dose on Day 1; Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Day 15; Pre-dose, 2, 4 and 6 hours post-dose on Day 22

Secondary outcomes (66)

  1. Part A: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-related TEAEs and Serious TEAEs According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0

    An Adverse Event(AE) is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended sign, symptom, or disease associated with the use of a medicinal product, regardless if it is considered related to the medicinal product. Serious AE: AE that resulted in death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to study intervention. Number of participants with TEAEs, treatment related TEAEs and serious TEAEs were reported.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 516 days)

  2. Part B: Number of Participants With Treatment-Emergent Adverse Events, Treatment-related TEAEs and Serious TEAEs According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0

    An Adverse Event(AE) is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended sign, symptom, or disease associated with the use of a medicinal product, regardless if it is considered related to the medicinal product. Serious AE: AE that resulted in death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to study intervention. Number of participants with TEAEs, treatment related TEAEs and serious TEAEs were reported.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 513 Days)

  3. Part FE: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-related TEAEs and Serious TEAEs According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0

    An Adverse Event(AE) is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended sign, symptom, or disease associated with the use of a medicinal product, regardless if it is considered related to the medicinal product. Serious AE: AE that resulted in death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to study intervention. Number of participants with TEAEs, treatment related TEAEs and serious TEAEs were reported.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 404 Days)

  4. Part A: Number of Participants With Abnormalities Grade Greater Than or Equals to (>=) 3 in Laboratory Test Values

    The laboratory measurements included hematology and biochemistry values were graded with National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 toxicity grades (where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening and Grade 5 = death). Number of participants with abnormalities Grade >= 3 in laboratory test values were reported.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 516 days)

  5. Part B: Number of Participants With Abnormalities Grade Greater Than or Equals to (>=) 3 in Laboratory Test Values

    The laboratory measurements included hematology and biochemistry values were graded with National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 toxicity grades (where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening and Grade 5 = death). Number of participants with abnormalities Grade >= 3 in laboratory test values were reported.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 513 Days)

  6. Part FE: Number of Participants With Abnormalities Grade Greater Than or Equals to (>=) 3 in Laboratory Test Values

    The laboratory measurements included hematology and biochemistry values were graded with National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 toxicity grades (where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening and Grade 5 = death). Number of participants with abnormalities Grade >= 3 in laboratory test values were reported.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 404 Days)

  7. Part A: Number of Participants With Clinically Meaningful Change From Baseline in Electrocardiogram (ECG)

    Number of participants with clinically meaningful change from baseline in ECG parameters were reported. Clinically Meaningful Change was decided by the investigator. The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. The parameters included heart rate (HR), Respiratory Rate, Pulse Rate, QRS, QT and QTcB calculated by the Bazett formula.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 516 days)

  8. Part B: Number of Participants With Clinically Meaningful Change From Baseline in Electrocardiogram (ECG)

    Number of participants with clinically meaningful change from baseline in ECG parameters were reported. Clinically Meaningful Change was decided by the investigator. The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. The parameters included heart rate (HR), Respiratory Rate, Pulse Rate, QRS, QT and QTcB calculated by the Bazett formula.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 513 Days)

  9. Part FE: Number of Participants With Clinically Meaningful Change From Baseline in Electrocardiogram (ECG)

    Number of participants with clinically meaningful change from baseline in ECG parameters were reported. Clinically Meaningful Change was decided by the investigator. The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. The parameters included heart rate (HR), Respiratory Rate, Pulse Rate, QRS, QT and QTcB calculated by the Bazett formula.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 404 Days)

  10. Part A: Number of Participants With Clinically Meaningful Change From Baseline in Vital Signs

    Number of participants with clinically meaningful change from baseline in vital signs. Clinically Meaningful Change was decided by the investigator. Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 516 days)

  11. Part B: Number of Participants With Clinically Meaningful Change From Baseline in Vital Signs

    Number of participants with clinically meaningful change from baseline in vital signs. Clinically Meaningful Change was decided by the investigator. Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 513 Days)

  12. Part FE: Number of Participants With Clinically Meaningful Change From Baseline in Vital Signs

    Number of participants with clinically meaningful change from baseline in vital signs. Clinically Meaningful Change was decided by the investigator. Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 404 Days)

  13. Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score

    ECOG PS score is widely used by doctors and researchers to assess how a participants disease is progressing and is used to assess how the disease affects the daily living abilities of the participant and determine appropriate treatment and prognosis. The score ranges from Grade0 to Grade5, where Grade0=Fully active, able to carry on all pre-disease performance without restriction, Grade1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (like light house work, office work), Grade2 = Ambulatory and capable of all self-care but unable to carry out any work activities, Grade3=Capable of only limited self-care, confined to bed or chair more than 50% of waking hours and Grade4=Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair, Grade5=Death.ECOG performance status was reported in terms of number of participants with baseline value vs worst post-baseline value.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 516 days)

  14. Part B:Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score

    ECOG PS score is widely used by doctors and researchers to assess how a participants disease is progressing and is used to assess how the disease affects the daily living abilities of the participant and determine appropriate treatment and prognosis. The score ranges from Grade0 to Grade5, where Grade0=Fully active, able to carry on all pre-disease performance without restriction, Grade1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (like light house work, office work), Grade2 = Ambulatory and capable of all self-care but unable to carry out any work activities, Grade3=Capable of only limited self-care, confined to bed or chair more than 50% of waking hours and Grade4=Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair, Grade5=Death.ECOG performance status was reported in terms of number of participants with baseline value vs worst post-baseline value.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 513 Days)

  15. Part FE: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score

    ECOG PS score is widely used by doctors and researchers to assess how a participants disease is progressing and is used to assess how the disease affects the daily living abilities of the participant and determine appropriate treatment and prognosis. The score ranges from Grade0 to Grade5, where Grade0=Fully active, able to carry on all pre-disease performance without restriction, Grade1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (like light house work, office work), Grade2 = Ambulatory and capable of all self-care but unable to carry out any work activities, Grade3=Capable of only limited self-care, confined to bed or chair more than 50% of waking hours and Grade4=Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair, Grade5=Death.ECOG performance status was reported in terms of number of participants with baseline value vs worst post-baseline value.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 404 Days)

  16. Part A: Single Dose: Maximum Observed Plasma Concentration (Cmax) of M3814

    Cmax was obtained directly from the concentration versus time curve.

    Measured: Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Day 1

  17. Part A: Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of M3814

    Cmax was obtained directly from the concentration versus time curve.

    Measured: Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Day 15

  18. Part B: Single Dose: Maximum Observed Drug Concentration (Cmax) of M3814

    Cmax was obtained directly from the concentration versus time curve.

    Measured: Pre-dose, 1, 2, 4 and 6 hour post-dose on Day 1

  19. Part B: Multiple Dose: Maximum Observed Drug Concentration (Cmax) of M3814

    Cmax was obtained directly from the concentration versus time curve.

    Measured: Pre-dose, 1, 2, 4 and 6 hour post-dose on Day 10

  20. Part A: Single Dose: Time to Reach the Maximum Plasma Concentration (Tmax) of M3814

    Tmax was obtained directly from the concentration versus time curve.

    Measured: Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Day 15

  21. Part A: Multiple Dose: Time to Reach the Maximum Plasma Concentration (Tmax) of M3814

    Tmax was obtained directly from the concentration versus time curve.

    Measured: Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Day 15

  22. Part B: Single Dose: Time to Reach the Maximum Plasma Concentration (Tmax) of M3814

    Tmax was obtained directly from the concentration versus time curve postdose.

    Measured: Pre-dose, 2, 4 and 6 hours post-dose on Day 10

  23. Part B: Multiple Dose: Time to Reach the Maximum Plasma Concentration (Tmax) of M3814

    Tmax was obtained directly from the concentration versus time curve postdose.

    Measured: Pre-dose, 2, 4 and 6 hours post-dose on Day 10

  24. Part A: Minimum Observed Drug Concentration (Cmin) of M3814

    Cmin is minimum observed plasma concentration obtained directly from the concentration versus time curve.

    Measured: Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Day 1

  25. Part B: Minimum Observed Drug Concentration (Cmin) of M3814

    Cmin is minimum observed plasma concentration obtained directly from the concentration versus time curve.

    Measured: Pre-dose, 1, 2, 4 and 6 hour post-dose on Day 1

  26. Part A: Average Plasma Concentration of M3814 Observed Post-dose (Cavg)

    Cavg is the average plasma concentration within 1 dosing interval obtained directly from the concentration versus time curve.

    Measured: Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Day 1

  27. Part B: Average Plasma Concentration of M3814 Observed Post-dose (Cavg)

    Cavg is the average plasma concentration within 1 dosing interval obtained directly from the concentration versus time curve.

    Measured: Pre-dose, 1, 2, 4 and 6 hour post-dose on Day 1

  28. Part A: Fluctuation Index of M3814

    Fluctuation index is defined as percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100*([Cmax Cmin]/Cavg).

    Measured: Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Day 1

  29. Part B: Fluctuation Index of M3814

    Fluctuation index is defined as percentage fluctuation (variation between maximum and minimum concentration at steady state), calculated as: 100*([Cmax Cmin]/Cavg).

    Measured: Pre-dose, 1, 2, 4 and 6 hour post-dose on Day 1

  30. Part A: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) of M3814

    Area under the serum concentration-time curve (AUC) from time zero to the last sampling time point at which the concentration is at or above lower limit of quantification (LLOQ).

    Measured: Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Day 1

  31. Part B: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) of M3814

    Area under the serum concentration-time curve (AUC) from time zero to the last sampling time point at which the concentration is at or above lower limit of quantification (LLOQ).

    Measured: Pre-dose, 1, 2, 4 and 6 hour post-dose on Day 1

  32. Part A: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M3814

    Area under the serum concentration-time curve from time zero to infinity (AUC0-inf). AUC0-inf calculated as AUC0-t + AUCextra. AUCextra represents the extrapolated part of AUC0-inf.

    Measured: Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Day 1

  33. Part B: Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M3814

    Area under the serum concentration-time curve from time zero to infinity (AUC0-inf). AUC0-infcalculated as AUC0-t + AUCextra.

    Measured: Pre-dose, 1, 2, 4 and 6 hour post-dose on Day 1

  34. Part A: Accumulation Ratio of Maximum Observed Drug Concentration [Racc(Cmax)] of M3814

    Accumulation ratio of Cmax was calculated as Cmax, after dosing on Day 15 divided by Cmax, after dosing on Day 1.

    Measured: Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Days 1 and 15

  35. Part B: Accumulation Ratio of Cmax [Racc(Cmax)] of M3814

    Accumulation ratio of Cmax was calculated as Cmax, after dosing on Day 10 divided by Cmax, after dosing on Day 1.

    Measured: Pre-dose, 1, 2, 4 and 6 hour post-dose on Day 1;Pre-dose, 2, 4 and 6 hours post-dose on Day 10

  36. Part A: Accumulation Ratio of AUC [Racc (AUC 0-12)] of M3814

    Accumulation ratio of AUC0-12 was calculated as AUC0-t, after dosing on Day 15 divided by AUC0-t, after dosing on Day 1.

    Measured: Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Days 1 and 15

  37. Part B: Accumulation Ratio of AUC [Racc (AUC 0-24)] of M3814

    Accumulation ratio of AUC0-12 was calculated as AUC0-t, after dosing on Day 10 divided by AUC0-t, after dosing on Day 1.

    Measured: Pre-dose, 1, 2, 4 and 6 hour post-dose on Day 1; Pre-dose, 2, 4 and 6 hours post-dose on Day 10

  38. Part A: Single Dose: Apparent Terminal Half-life (t1/2) of M3814

    T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve.

    Measured: Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Day 15

  39. Part A: Multiple Doses: Apparent Terminal Half-life (t1/2) of M3814

    T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve.

    Measured: Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Day 15

  40. Part B: Single Dose: Apparent Terminal Half-life (t1/2) of M3814

    T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve.

    Measured: Pre-dose, 1, 2, 4 and 6 hour post-dose on Day 1;Pre-dose, 2, 4 and 6 hours post-dose on Day 10

  41. Part B: Multiple Dose: Apparent Terminal Half-life (t1/2) of M3814

    T1/2 was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve.

    Measured: Pre-dose, 1, 2, 4 and 6 hour post-dose on Day 1;Pre-dose, 2, 4 and 6 hours post-dose on Day 10

  42. Part A: Apparent Volume of Distribution During Terminal Phase (Vz/f) of M3814

    The apparent volume of distribution during the terminal phase following extravascular administration, based on the fraction of dose absorbed. Vz/f = Dose/(AUC0-inf multiplied by Lambda z).

    Measured: Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Day 1

  43. Part B: Apparent Volume of Distribution During Terminal Phase (Vz/f) of M3814

    The apparent volume of distribution during the terminal phase following extravascular administration, based on the fraction of dose absorbed. Vz/f = Dose/(AUC0-inf multiplied by Lambda z).

    Measured: Pre-dose, 1, 2, 4 and 6 hour post-dose on Day 1

  44. Part A: Apparent Clearance (CL/f) of M3814

    Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

    Measured: Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Day 1

  45. Part B: Apparent Clearance (CL/f) of M3814

    Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

    Measured: Pre-dose, 1, 2, 4 and 6 hour post-dose on Day 1

  46. Part A: Terminal Elimination Rate Constant (Lambda z) of M3814

    Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.

    Measured: Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Day 1

  47. Part B: Terminal Elimination Rate Constant (Lambda z) of M3814

    Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.

    Measured: Pre-dose, 1, 2, 4 and 6 hour post-dose on Day 1

  48. Part A: Number of Participants With Positive Antidrug Antibody (ADA)

    Blood samples were analyzed by a validated homogenous bridging electrochemiluminescence assay to detect the presence of antidrug antibodies (ADA). Number of participants with positive ADA were reported.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 516 Days)

  49. Part B: Number of Participants With Positive Antidrug Antibody (ADA)

    Blood samples were analyzed by a validated homogenous bridging electrochemiluminescence assay to detect the presence of antidrug antibodies (ADA). Number of participants with positive ADA were reported.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 513 Days)

  50. Part FE: Number of Participants With Positive Antidrug Antibody (ADA)

    Serum samples were analyzed by a validated assay method to detect the presence of antidrug antibodies (ADA). Number of participants with positive ADA were reported.

    Measured: Part FE: From the first study intervention to 508 days

  51. Part A: Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

    Confirmed BOR was defined as the percentage of participants who achieved confirmed complete responses (CR) or partial response (PR), according to RECIST version 1.1 assessed by the Investigator.CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of disease (PD) nor sufficient shrinkage to qualify for PR. PD: At least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Confirmed CR=as at least two determinations of CR at least 4 weeks apart with no PD. Confirmed PR=as at least 2 determinations of PR or better (PR followed by PR or PR followed by CR), at least 4 weeks apart (not qualifying for a CR) with no PD in between. Percentage of Participants with confirmed BOR were reported.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 516 Days)

  52. Part B: Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

    Confirmed BOR was defined as the percentage of participants who achieved confirmed complete responses (CR) or partial response (PR), according to RECIST version 1.1 assessed by the Investigator.CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of disease (PD) nor sufficient shrinkage to qualify for PR. PD: At least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Confirmed CR=as at least two determinations of CR at least 4 weeks apart with no PD. Confirmed PR=as at least 2 determinations of PR or better (PR followed by PR or PR followed by CR), at least 4 weeks apart (not qualifying for a CR) with no PD in between. Percentage of Participants with confirmed BOR were reported.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 513 Days)

  53. Part FE: Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

    Confirmed BOR was defined as the percentage of participants who achieved confirmed complete responses (CR) or partial response (PR), according to RECIST version 1.1 assessed by the Investigator.CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of disease (PD) nor sufficient shrinkage to qualify for PR. PD: At least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Confirmed CR=as at least two determinations of CR at least 4 weeks apart with no PD. Confirmed PR=as at least 2 determinations of PR or better (PR followed by PR or PR followed by CR), at least 4 weeks apart (not qualifying for a CR) with no PD in between. Percentage of Participants with confirmed BOR were reported.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 404 Days)

  54. Part A: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator

    DOR was defined for participants with confirmed response, as the time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

    Measured: Time from first documentation of objective response until date of first documentation of PD or death due to any cause, whichever occurred first, assessed up to 516 Days

  55. Part B: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator

    DOR was defined for participants with confirmed response, as the time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

    Measured: Time from first documentation of objective response until date of first documentation of PD or death due to any cause, whichever occurred first, assessed up to 513 Days

  56. Part FE: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator

    DOR was defined for participants with confirmed response, as the time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

    Measured: Time from first documentation of objective response until date of first documentation of PD or death due to any cause, whichever occurred first, assessed up to 44 Weeks

  57. Part A: Progression-free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator

    Progression-Free Survival was calculated as the time from the start of any study intervention to the date of first documentation of objective progression of disease or death due to any cause, whichever occurs first. PD: At least a 20 percent (%) increase in the sum of the longest diameter (SLD) taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. The PFS was analyzed by using the Kaplan-Meier method.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 516 Days)

  58. Part B: Progression-free Survival (PFS) Time According to RECIST v 1.1 Assessed by Investigator

    Progression-Free Survival was calculated as the time from the start of any study intervention to the date of first documentation of objective progression of disease or death due to any cause, whichever occurs first. PD: At least a 20 percent (%) increase in the sum of the longest diameter (SLD) taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. The PFS was analyzed by using the Kaplan-Meier method.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 513 Days)

  59. Part FE: Progression-free Survival (PFS) Time According to RECIST v 1.1 Assessed by Investigator

    Progression-Free Survival was calculated as the time from the start of any study intervention to the date of first documentation of objective progression of disease or death due to any cause, whichever occurs first. PD: At least a 20 percent (%) increase in the sum of the longest diameter (SLD) taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. The PFS was analyzed by using the Kaplan-Meier method.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 404 Days)

  60. Part A: Overall Survival

    Overall survival was defined as the time from treatment start to the date of death, regardless of the actual cause of the participant's death. The overall survival was analyzed by using the Kaplan-Meier method. Median, is estimated by Kaplan-Meier method which stands for the time that half of the participants are expected to be alive. Depending on the observed number of deaths, time of censoring for each participant, median survival time may not be reached or estimated (few deaths will lead the KM curve never crosses 50% survival line), hence median was not calculable for Part A: M3814 250 mg BID + Avelumab 800 mg Q2W arm. Participants that are still alive at the time of analysis will be censored and counted into the analysis.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 1359 Days)

  61. Part B: Overall Survival

    Overall survival was defined as the time from treatment start to the date of death, regardless of the actual cause of the participant's death. The overall survival was analyzed by using the Kaplan-Meier method. Median, is estimated by Kaplan-Meier method which stands for the time that half of the participants are expected to be alive. Depending on the observed number of deaths, time of censoring for each participant, median survival time may not be reached or estimated (few deaths will lead the KM curve never crosses 50% survival line), hence median was not calculable for Part B of the study. Participants that are still alive at the time of analysis will be censored and counted into the analysis.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 1359 Days)

  62. Part FE: Overall Survival

    Overall survival was defined as the time from treatment start to the date of death, regardless of the actual cause of the participant's death. The overall survival was analyzed by using the Kaplan-Meier method. Participants that are still alive at the time of analysis will be censored and counted into the analysis.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 1359 Days)

  63. Part A: Best Percent Change From Baseline in Tumor Size According to RECIST v 1.1

    Tumor size is derived as the best percent change from baseline in target lesions (sum of longest diameter for non-nodal lesions and short axis for nodal lesions) at each time point.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 516 Days)

  64. Part B: Best Percent Change From Baseline in Tumor Size According to RECIST v 1.1

    Tumor size is derived as the best percent change from baseline in target lesions (sum of longest diameter for non-nodal lesions and short axis for nodal lesions) at each time point.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 513 Days)

  65. Part FE: Best Percent Change From Baseline in Tumor Size According to RECIST v 1.1

    Tumor size is derived as the best percent change from baseline in target lesions (sum of longest diameter for non-nodal lesions and short axis for nodal lesions) at each time point.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 404 Days)

  66. Part B: Number of Participants With Radiotherapy (RT)-Induced Toxicity According to NCI-CTCAE v 5.0

    Number of participants with radiotherapy-induced toxicities (mucositis and radiation dermatitis) were reported.

    Measured: Time from first study intervention up to long term safety follow-up period (Up to 512.4 Days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Oct 2018
  2. Study start27 Nov 2018
  3. Primary completion1 Sep 2021
  4. Study completion17 Aug 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
57 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03724890
Sponsor's protocol ID
MS201964_0001
Status last verified
Apr 2025
First submitted
29 Oct 2018
Last updated
10 Apr 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports 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 bit.ly/IPD21

Publications

  • Perez B, Aljumaily R, Marron TU, Shafique MR, Burris H, Iams WT, Chmura SJ, Luke JJ, Edenfield W, Sohal D, Liao X, Boesler C, Machl A, Seebeck J, Becker A, Guenther B, Rodriguez-Gutierrez A, Antonia SJ. Phase I study of peposertib and avelumab with or without palliative radiotherapy in patients with advanced solid tumors. ESMO Open. 2024 Feb;9(2):102217. doi: 10.1016/j.esmoop.2023.102217. Epub 2024 Feb 5.

    PubMed 38320431

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing M3814, Avelumab and Radiotherapy in people with Oncology and Solid Tumors, run by EMD Serono Research & Development Institute, Inc. at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) Assessed Using National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Version 5.0 (time frame: Day 1 up to Day 21). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03724890, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2025.

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