Study of Avelumab-M3814 Combinations

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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

Cmax was obtained directly from the concentration versus time curve.

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

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

Cmax was obtained directly from the concentration versus time curve.

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

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

Cmax was obtained directly from the concentration versus time curve.

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

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

Cmax was obtained directly from the concentration versus time curve.

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

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

Tmax was obtained directly from the concentration versus time curve.

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

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

Tmax was obtained directly from the concentration versus time curve.

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

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.

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

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.

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

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

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

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

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

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

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

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.

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

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.

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

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).

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

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).

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

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).

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

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).

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

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.

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

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.

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

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.

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

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.

Time frame: 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

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.

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

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.

Time frame: 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

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.

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

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.

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

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.

Time frame: 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

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.

Time frame: 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

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).

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

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).

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

Time frame: Part FE: From the first study intervention to 508 days

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.

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

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.

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

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.

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

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.

Time frame: 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

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.

Time frame: 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

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.

Time frame: 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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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