Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
M4344 BIW · 1 trial · 2 indications
An AE is defined as 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 (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, regardless if it is considered related to the medicinal product. Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs are defined as AEs that were reported or worsened on or after start of study drug dosing through the Safety Follow-up Visit. TEAEs included both serious TEAEs and non-serious TEAEs.
Laboratory parameters: hematology and chemistry. Blood samples were collected for analysis of following hematology parameters: Hemoglobin, Erythrocytes, mean corpuscular hemoglobin (MCH), MCH concentration, Mean corpuscular volume, Reticulocytes, Platelets, Leukocytes, Eosinophils, Basophils, Neutrophils, Lymphocytes, Monocytes. Blood samples were collected for analysis of following chemistry parameters: Glucose, Blood urea nitrogen/Urea, Creatinine, Sodium, Potassium, Calcium, Chloride, Magnesium, Bicarbonate, Inorganic phosphate, Total bilirubin, Direct bilirubin, Total protein, Albumin, Creatine kinase, Alkaline phosphatase, Aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Uric acid, Thyroid stimulating hormone. Number of participants with Grade 3 or 4 (\>20% of total) in laboratory parameters were reported as per NCI-CTCAE v4.0 graded from Grade 1 to 5. Grade 1: Mild, Grade 2: Moderate; Grade 3: Severe. Grade 4: Life-threatening and Grade 5: Death.
Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically relevant findings in vital signs were reported. Clinical relevance was decided by Investigator.
ECG parameters included PR interval, RR interval, QT interval, QRS duration, QTc intervals (derived using Fridericia's correction method) and heart rate. A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 5 minutes using an ECG machine. Clinical significance was decided by investigator. Number of participants with clinically significant abnormalities in 12-Lead ECGs were reported.
MTD as per NCI-CTCAE v4.0 is defined as highest dose for a given schedule at which there is no more than 1 dose- limiting toxicity (DLT) in 6 participants. DLT: as related/possibly drug-related: Neutropenia Grade (Gr)4 for \> 7 days duration/requiring hemopoietic growth factors; Febrile neutropenia; Infection with Gr3/4 neutropenia; Thrombocytopenia Gr3; Thrombocytopenia Gr4 for \> 7 days duration/requiring hemopoietic growth factors; Gr3/4 toxicity to organs other than bone marrow; Gr3/4 increase in bilirubin unless increase is due to inhibition of bilirubin glucuronidation; Death due to drug-related complications; Cardiac: QTc prolongation, Gr2/greater ventricular arrhythmia, severe sustained/symptomatic sinus bradycardia, persistent supraventricular arrhythmia, Symptoms suggestive of congestive heart failure, Troponin-T level consistent with myocardial infarction; drug-related toxicity causes interruption of treatment for \> 2 weeks.
An AE is defined as 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 (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, regardless if it is considered related to the medicinal product. Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs are defined as AEs that were reported or worsened on or after start of study drug dosing through the Safety Follow-up Visit. TEAEs included both serious TEAEs and non-serious TEAEs.
Laboratory parameters: hematology and chemistry. Blood samples were collected for analysis of following hematology parameters: Hemoglobin, Erythrocytes, mean corpuscular hemoglobin (MCH), MCH concentration, Mean corpuscular volume, Reticulocytes, Platelets, Leukocytes, Eosinophils, Basophils, Neutrophils, Lymphocytes, Monocytes. Blood samples were collected for analysis of following chemistry parameters: Glucose, Blood urea nitrogen/Urea, Creatinine, Sodium, Potassium, Calcium, Chloride, Magnesium, Bicarbonate, Inorganic phosphate, Total bilirubin, Direct bilirubin, Total protein, Albumin, Creatine kinase, Alkaline phosphatase, Aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Uric acid, Thyroid stimulating hormone. Number of participants with Grade 3 or 4 (\>20% of total) in laboratory parameters were reported as per NCI-CTCAE v5.0 graded from Grade 1 to 5. Grade 1: Mild, Grade 2: Moderate; Grade 3: Severe. Grade 4: Life-threatening and Grade 5: Death.
Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically relevant findings were reported. Clinical relevance was decided by Investigator.
ECG parameters included PR interval, RR interval, QT interval, QRS duration, QTc intervals (derived using Fridericia's correction method) and heart rate. A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 5 minutes using an ECG machine. Clinical Significance was determined by investigator. Number of participants with clinically significant abnormalities in 12-lead ECGs were reported.
MTD as per NCI-CTCAE v5.0 is defined as highest dose for a given schedule at which there is no more than 1 dose- limiting toxicity (DLT) in 6 participants. DLT: as related/possibly drug-related: Neutropenia Grade (Gr)4 for \> 7 days duration/requiring hemopoietic growth factors; Febrile neutropenia; Infection with Gr3/4 neutropenia; Thrombocytopenia Gr3; Thrombocytopenia Gr4 for \> 7 days duration/requiring hemopoietic growth factors; Gr3/4 toxicity to organs other than bone marrow; Gr3/4 increase in bilirubin unless increase is due to inhibition of bilirubin glucuronidation; Death due to drug-related complications; Cardiac: QTc prolongation, Gr2/greater ventricular arrhythmia, severe sustained/symptomatic sinus bradycardia, persistent supraventricular arrhythmia, Symptoms suggestive of congestive heart failure, Troponin-T level consistent with myocardial infarction; drug-related toxicity causes interruption of treatment for \> 2 weeks.
An AE is defined as 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 (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, regardless if it is considered related to the medicinal product. Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs are defined as AEs that were reported or worsened on or after start of study drug dosing through the Safety Follow-up Visit. TEAEs included both serious TEAEs and non-serious TEAEs.
Laboratory parameters: hematology and chemistry. Blood samples were collected for analysis of following hematology parameters: Hemoglobin, Erythrocytes, mean corpuscular hemoglobin (MCH), MCH concentration, Mean corpuscular volume, Reticulocytes, Platelets, Leukocytes, Eosinophils, Basophils, Neutrophils, Lymphocytes, Monocytes. Blood samples were collected for analysis of following chemistry parameters: Glucose, Blood urea nitrogen/Urea, Creatinine, Sodium, Potassium, Calcium, Chloride, Magnesium, Bicarbonate, Inorganic phosphate, Total bilirubin, Direct bilirubin, Total protein, Albumin, Creatine kinase, Alkaline phosphatase, Aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Uric acid, Thyroid stimulating hormone. Number of participants with Grade 3 or 4 (\>20% of total) in laboratory parameters were reported as per NCI-CTCAE v4.0 graded from Grade 1 to 5. Grade 1: Mild, Grade 2: Moderate; Grade 3: Severe. Grade 4: Life-threatening and Grade 5: Death.
Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically relevant findings in vital signs were reported. Clinical relevance was decided by Investigator.
ECG parameters included PR interval, RR interval, QT interval, QRS duration, QTc intervals (derived using Fridericia's correction method) and heart rate. A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 5 minutes using an ECG machine. Clinical significance was determined by Investigator. Number of participants with clinically significant abnormalities in 12-lead ECGs were reported.
MTD as per NCI-CTCAE v4.0 is defined as highest dose for a given schedule at which there is no more than 1 dose- limiting toxicity (DLT) in 6 participants. DLT: as related/possibly drug-related: Neutropenia Grade (Gr)4 for \> 7 days duration/requiring hemopoietic growth factors; Febrile neutropenia; Infection with Gr3/4 neutropenia; Thrombocytopenia Gr3; Thrombocytopenia Gr4 for \> 7 days duration/requiring hemopoietic growth factors; Gr3/4 toxicity to organs other than bone marrow; Gr3/4 increase in bilirubin unless increase is due to inhibition of bilirubin glucuronidation; Death due to drug-related complications; Cardiac: QTc prolongation, Gr2/greater ventricular arrhythmia, severe sustained/symptomatic sinus bradycardia, persistent supraventricular arrhythmia, Symptoms suggestive of congestive heart failure, Troponin-T level consistent with myocardial infarction; drug-related toxicity causes interruption of treatment for \> 2 weeks.
AE: 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 (including an abnormal laboratory finding), symptom/disease temporally associated with use of a medicinal product, regardless if it is considered related to medicinal product. Serious AE: AE that resulted in any of following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: AEs that were reported/worsened on/after start of study drug dosing through the Safety Follow-up Visit. TEAEs included both serious TEAEs and non-serious TEAEs. Treatment related AEs: reasonably related to the study drug/study treatment. AE could medically (pharmacologically/clinically) be attributed to the study drug/study treatment under study in this clinical study protocol.
Laboratory parameters: hematology and chemistry. Blood samples were collected for analysis of following hematology parameters: Hemoglobin, Erythrocytes, mean corpuscular hemoglobin (MCH), MCH concentration, Mean corpuscular volume, Reticulocytes, Platelets, Leukocytes, Eosinophils, Basophils, Neutrophils, Lymphocytes, Monocytes. Blood samples were collected for analysis of following chemistry parameters: Glucose, Blood urea nitrogen/Urea, Creatinine, Sodium, Potassium, Calcium, Chloride, Magnesium, Bicarbonate, Inorganic phosphate, Total bilirubin, Direct bilirubin, Total protein, Albumin, Creatine kinase, Alkaline phosphatase, Aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Uric acid, Thyroid stimulating hormone. Number of participants with Grade 3 or 4 (\>20% of total) in laboratory parameters were reported as per NCI-CTCAE v5.0 graded from Grade 1 to 5. Grade 1: Mild, Grade 2: Moderate; Grade 3: Severe. Grade 4: Life-threatening and Grade 5: Death.
Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically relevant findings in vital signs were reported. Clinical relevance was decided by Investigator.
ECG parameters included PR interval, RR interval, QT interval, QRS duration, QTc intervals (derived using Fridericia's correction method) and heart rate. A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 5 minutes using an ECG machine. Clinical significance was determined by investigator. Number of participants with clinically significant abnormalities in 12-lead ECGs were reported.
OR is defined as the confirmed assessment of best overall response of complete response (CR) or partial response (PR). CR is defined as disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
| Arm | Type | Description |
|---|---|---|
| Part A: M4344 10 mg BIW | EXPERIMENTAL | Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| Part A: M4344 20 mg BIW | EXPERIMENTAL | Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| Part A: M4344 40 mg BIW | EXPERIMENTAL | Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| Part A: M4344 80 mg BIW | EXPERIMENTAL | Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| Part A: M4344 160 mg BIW | EXPERIMENTAL | Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| Part A: M4344 300 mg BIW | EXPERIMENTAL | Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| Part A: M4344 450 mg BIW | EXPERIMENTAL | Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| Part A: M4344 700 mg BIW | EXPERIMENTAL | Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| Part A: M4344 1050 mg BIW | EXPERIMENTAL | Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| Part A: M4344 1200 mg BIW | EXPERIMENTAL | Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| Part A2: M4344 100 mg BID | EXPERIMENTAL | Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| Part A2: M4344 150 mg QD | EXPERIMENTAL | Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| Part A2: M4344 250 mg QD | EXPERIMENTAL | Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| Part A2: M4344 350 mg QD | EXPERIMENTAL | Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| Part B1: M4344 350 mg + Carboplatin | EXPERIMENTAL | Participants received M4344 at a dose of 350 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of Area under the concentration versus time curve 5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| Part B1: M4344 400 mg + Carboplatin | EXPERIMENTAL | Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| Part B1: M4344 500 mg + Carboplatin | EXPERIMENTAL | Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 in combination with intravenous infusion of Carboplatin at a dose of AUC5 on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| Part C: M4344 250 mg QD | EXPERIMENTAL | Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| Name | Type | Description |
|---|---|---|
| M4344 10 mg BIW | DRUG | Participants received M4344 at a dose of 10 milligrams (mg) orally twice weekly (BIW) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| M4344 20 mg BIW | DRUG | Participants received M4344 at a dose of 20 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| M4344 40 mg BIW | DRUG | Participants received M4344 at a dose of 40 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| M4344 80 mg BIW | DRUG | Participants received M4344 at a dose of 80 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| M4344 160 mg BIW | DRUG | Participants received M4344 at a dose of 160 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| M4344 300 mg BIW | DRUG | Participants received M4344 at a dose of 300 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| M4344 450 mg BIW | DRUG | Participants received M4344 at a dose of 450 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| M4344 700 mg BIW | DRUG | Participants received M4344 at a dose of 700 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| M4344 1050 mg BIW | DRUG | Participants received M4344 at a dose of 1050 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| M4344 1200 mg BIW | DRUG | Participants received M4344 at a dose of 1200 mg orally BIW until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| M4344 100 mg BID | DRUG | Participants received M4344 at a dose of 100 mg orally twice daily (BID) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| M4344 150 mg QD | DRUG | Participants received M4344 at a dose of 150 mg orally once daily (QD) until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| M4344 250 mg QD | DRUG | Participants received M4344 at a dose of 250 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| M4344 350 mg QD | DRUG | Participants received M4344 at a dose of 350 mg orally QD until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| M4344 400 mg | DRUG | Participants received M4344 at a dose of 400 mg orally on Day 2 and Day 9 until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| M4344 500 mg | DRUG | Participants received M4344 at a dose of 500 mg orally on Day 2 and Day 9 until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
| Carboplatin | DRUG | Participants received intravenous infusion of Carboplatin at a dose of Area Under Curve5 (AUC5) on Day 1 of 21-day cycle until disease progression, death, unacceptable toxicity, new anticancer treatment was started, or study withdrawal. |
Inclusion Criteria: * Part A, A2 and A3: Participants with one histologically or cytologically confirmed malignant advanced solid tumor, for which no standard therapy is available which may convey clinical benefit * Part B1: Participants with one histologically or cytologically confirmed malignant ...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Merck & Co., Inc. | MRK | 3 | PHASE2 | Pembrolizumab, Gardasil 9 |
| Incyte Corporation | INCY | 1 | PHASE2 | Retifanlimab |
| Novartis AG Sponsored ADR | NVS | 1 | PHASE1 | KFA115 |
| Iovance Biotherapeutics Inc | IOVA | 2 | PHASE2 | Aldesleukin |
| AstraZeneca PLC | AZN | 1 | - | Trastuzumab deruxtecan |