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M6620

Phase 2

Advanced Solid Tumor | Small molecule | Oncology |Merck KGaA|Trials Updated: Nov 29, 2024

M6620 development status

Highest phase Phase 2 (NCT04768296)
Phase scored for MKGAFPhase 1
Registered trials 6 across 4 sponsors since Jun 2014

M6620 target and mechanism

ModalitySmall molecule

Also known as VX-970, [14C]Berzosertib, Berzosertib

Success Probability

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Market & Valuation

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Trial Design

CONTROLLED
Total Trials6
Total Enrollment322

FDA Designations

No designations recorded

M6620 clinical trials

M6620 · 6 trials · 7 indications

Phase 2 1Phase 1 5
NCT04768296Berzosertib + Topotecan in Relapsed Platinum-Resistant Small-Cell Lung Cancer (DDRiver SCLC 250)Small-cell Lung Cancer
COMPLETED76 Analytics
PHASE2COMPLETED
Berzosertib + Topotecan in Relapsed Platinum-Resistant Small-Cell Lung Cancer (DDRiver SCLC 250)
Small-cell Lung CancerUnlock trial analytics

Study Endpoints

Primary Endpoints

Main Part: Objective Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Independent Review Committee (IRC)
Time from first administration of study treatment up to 27.7 months

Objective response rate was defined as percentage of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD). CR: Disappearance of all target and non-target lesions. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of their diameters, and no unequivocal progression of non-target lesions. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on the study, or unequivocal progression of non-target lesions, or appearance of any new lesion.

Safety Run-in Part: Number of Participants With Dose Limiting Toxicities (DLTs)
Up to Cycle 1 Day 21 (each cycle is of 21 days)

DLT is defined as drug-related: Neutropenia Grade 4 for greater than (\>) 7 days' duration; Febrile neutropenia (that is \[i.e.\] absolute neutrophil count less than (\< ) 1000 per millimeter cube (mm\^3) with single temperature of \> 38.3°degree Celsius or a sustained temperature of greater than or equal to (\>=) 38 degree Celsius for more than 1 hour; Infection (documented clinically or microbiologically) with Grades 3 or 4 neutropenia; Thrombocytopenia \>= Grade 3; Grade \>= 3 non-hematological AEs.

Safety Run-in Part: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs
Time from first administration of study treatment up to 27.7 months

An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as events with onset date or worsening during the on-treatment period. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs is defined as reasonably related to the study intervention.

Safety Run-in Part: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Time from first administration of study treatment up to 27.7 months

Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically significant changes from baseline in vital signs were reported. Clinical significance was decided by Investigator.

Safety Run-in Part: Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings
Time from first administration of study treatment up to 27.7 months

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 changes from baseline in 12-Lead ECGs were reported.

Safety Run-in Part: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs)
Time from first administration of study treatment up to 27.7 months

The laboratory measurements included hematology and biochemistry. Number of participants with clinically significant abnormalities with Grade greater than or equals to (\>=) 3 in laboratory values reported as TEAEs as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 graded from Grade 1 to 5. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death. Clinically Significance was decided by investigator.

Period 1: Percent Urinary Recovery (Feurine) of Total Radioactivity
Predose, 0-4, 4-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose

Feurine, fractions of total radioactivity excreted in urine as percentage of the administered dose between time t1 (= start) and t2 (= end).

Period 1: Percent Fecal Recovery (Fefeces) of Total Radioactivity
Predose, 0-4, 4-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose

Fefeces, fractions of total radioactivity excreted in feces as percentage of the administered dose between time t1 (= start) and t2 (= end).

Period 1: Percent Total Recovery in Urine and Feces (Fetotal) of Total Radioactivity
Predose, 0-4, 4-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose

Fetotal, fractions of total radioactivity excreted in urine and feces as percentage of the administered dose between time t1 (= start) and t2 (= end).

Period 1: Maximum Observed Plasma Concentration (Cmax) of Berzosertib
Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose

Cmax was obtained directly from the plasma concentration versus time curve.

Period 1: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Berzosertib
Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose

Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.

Period 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Berzosertib
Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

Period 1: Terminal Elimination Half-Life (T1/2) of Berzosertib
Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose

Elimination Half Life (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 using linear regression method.

Period 1: Total Body Clearance (CL) of Berzosertib From Plasma
Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose

CL is a quantitative measure of the rate at which a drug substance is removed from the body, calculated as dose divided by AUC0-infinity.

Period 1: Apparent Volume of Distribution During the Terminal Phase (Vz) of Berzosertib
Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose

Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz was calculated by dividing the dose with area under the concentration time curve from time zero to infinity multiplied with terminal elimination rate constant Lambda(z). Vz = Dose/AUC0-inf multiply Lambda z.

Period 1: Apparent Volume of Distribution at Steady State (Vss) of Berzosertib
Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose

Vss is the theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it is in blood plasma at steady state.

Period 1: Maximum Observed Plasma Concentration (Cmax) of Total Radioactivity
Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose

Cmax was obtained directly from the plasma concentration versus time curve. Cmax of total radioactivity was calculated in nanogram equivalents per milliliter (ng eq)/mL.

Period 1: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Total Radioactivity
Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose

Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule. AUC0-t was calculated in hour\*nanogram equivalents per milliliter (h\*\[ng eq/mL\]).

Period 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Total Radioactivity
Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

Period 1: Terminal Elimination Half-Life (T1/2) of Total Radioactivity
Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose

Elimination Half Life (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 using linear regression method.

Period 1: Maximum Observed Blood Concentration (Cmax) of Total Radioactivity
Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose

Cmax was obtained directly from the blood concentration versus time curve.

Period 1: Area Under the Blood Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of Total Radioactivity
Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose

Area under the blood concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.

Period 1: Area Under the Blood Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Total Radioactivity
Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.

Period 1: Terminal Elimination Half-Life (T1/2) of Total Radioactivity in Blood
Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose

Elimination Half Life (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 using linear regression method.

Period 1: Cumulative Amount of Berzosertib Dose Excreted in Urine (Aeurine)
Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose

Aeurine is defined as the amount of Berzosertib excreted in urine over the time interval from t1 (= start) and t2 (= end).

Period 1: Percentage of Berzosertib Dose Excreted in Urine (Feurine)
Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose

Feurine is defined as the amount of Berzosertib unchanged excreted in urine as percentage of the administered dose over the time interval t1 (= start) and t2 (= end).

Period 1: Renal Clearance (CLr) of Berzosertib
Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours after dosing on Day 1, continued in 24-hour intervals, until discharge criteria are met, assessed up to Day 14 post-dose

Renal clearance was calculated as total amount of unchanged drug excreted in the urine between times t1 and t2 (Aeurine) divided by area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.

Part A: Number of Participants With Dose Limiting Toxicities (DLTs)
Up to 3 weeks

DLT: any death not clearly due to underlying disease/extraneous causes/Grade(Gr) \>=3 nonhematologic/Gr\>=4 hematologic toxicity that was probably/definitely related to any of study interventions, individually/combination that occurred during DLT observation period, except for any of following: Gr3 infusion-related reaction; Transient (\<=6hr) Gr3 flu-like symptoms/fever, controlled with medical management; Transient (\<=72hr) Gr3 fatigue, local reactions, headache, nausea/emesis; Gr3 diarrhea, skin toxicity, liver function test increase; Single laboratory values out of normal range and controlled with medical management; Tumor flare phenomenon: local pain, irritation/rash, localized at sites of known/suspected tumor; Neutropenia (Gr3/4) for \<7 days not associated with any infection; Gr3 thrombocytopenia for \<7 days without clinically significant bleeding and not requiring platelet transfusion; Symptomatic thyroid dysfunction manageable with treatment.

STAGE A1 - Number of Dose Limiting Toxicities for M6620 (Berzosertib) Administered Concomitantly With Radiotherapy (RT) in the Palliative Treatment of Oesophageal Cancer.
From start of M6620 (Berzosertib) treatment to 6-week follow up visit (9 weeks)

To determine the best tolerated M6620 (Berzosertib) treatment schedule (or phase II recommended dose, RPTD) administered concomitantly with radiotherapy (RT) only in the palliative treatment of oesophageal cancer.

STAGE A2 - Number of Dose Limiting Toxicities for M6620 (Berzosertib) Administered Concomitantly With Chemotherapy (Cisplatin and Capecitabine) in the Palliative Treatment of Solid Cancer.
From start of M6620 (Berzosertib) treatment to end of first week of cycle two of chemotherapy (4 weeks)

To determine the best tolerated M6620 (Berzosertib) treatment schedule (or phase II recommended dose, RPTD) administered concomitantly with chemotherapy (cisplatin and capecitabine) only in the palliative treatment of solid cancer.

STAGE B - To Determine the Best Tolerated M6620 (Berzosertib) Treatment Schedule (or RPTD) Administered Concomitantly With Radiotherapy (dCRT) in Combination With Cisplatin and Capecitabine in the Radical Treatment of Oesophageal Cancer.
24 weeks

Highest treatment schedule resulting in less than 45% dose limiting toxicity (DLT) rate.

Number of Participants With Adverse Events (AEs) and Treatment Related AEs
Up to 6 years

An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, regardless of causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Treatment-related AEs: reasonably related to the study intervention.

Parts A, B, B2, C1, C2, C3: Safety parameters, including adverse event (AEs), clinical laboratory values (serum chemistry, hematology, and urinalysis), vital signs, and electrocardiogram (ECG) assessments
Screening through Safety Follow-up (approximately 22 weeks)
Parts C1, C2, C3: Overall Response Rate (ORR) for all participants in Part C1 (NSCLC), ORR for participants in Part C2 (TNBC) who are basaloid subtype and BRCA1/BRCA2 germline wild-type, ORR for all participants in Part C3 (SCLC)
1 year

Secondary Endpoints

Main Part: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Independent Review Committee (IRC)
From first documented objective response to PD or death due to any cause, assessed up to 27.7 months
Main Part: Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Independent Review Committee (IRC)
Time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, assessed up to 27.7 months
Main Part: Overall Survival (OS)
Time from first administration of study treatment to the date of death, assessed up to 27.7 months
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Study Design & Arms

AllocationNON_RANDOMIZED
MaskingNONE
ModelSEQUENTIAL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Safety run-in Part (Dose Level1 [DL 1]): Berzosertib 105 mg/m^2 + Topotecan 1.25 mg/m^2EXPERIMENTALParticipants received Berzosertib at a dose of 105 milligrams per square meter (mg/m\^2 ) intravenously on Day 2 and Day 5 of each 21-daycycle in combination with Topotecan at a dose of 1.25mg/m\^2 intravenously on Days1 through 5 of each 21-day cycle in DL1 of safety run-in part until disease progression or other criteria for study intervention discontinuation are met.
Safety run-in Part (DL2) +Main Part: Berzosertib 210 mg/m^2 + Topotecan 1.25 mg/m^2EXPERIMENTALParticipants received Berzosertib at a dose of 210 mg/m\^2 intravenously on Day 2 and Day 5 of each 21-day cycle in combination with Topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in DL 1 and DL 2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met.
[14C]BerzosertibEXPERIMENTALParticipants received single intravenous infusion of\[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) on Day 1 in Period 1 and stay in clinical research unit (CRU) is required until the discharge criteria are met with a maximum confinement period of 15 days.
Berzosertib + TopotecanEXPERIMENTALParticipants received single intravenous infusion of Berzosertib at a dose of 210 mg/m\^2 on Day 2 and Day 5 in combination with topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in period 2 until disease progression or other criteria for study intervention discontinuation were met.
Part A: Carboplatin + M6620 + AvelumabEXPERIMENTAL -
Stage A1, A2 & BEXPERIMENTALThe trial is a single arm study. Different populations are recruited to each stage and the stages run independently of each other. Stage A1 \& A2 will commence before Stage B so that safety data can be obtained in the palliative setting prior to Stage B commencing. Stage A1 may be ongoing when Stage B begins. Each Stage has a separate eligibility criteria. Stage A1: M6620 \& palliative radiotherapy Stage A2: M6620 \& palliative chemotherapy (Cisplatin \& Capecitabine) Stage B: M6620 \& definitive chemoradiotherapy
Part A1: BerzosertibEXPERIMENTAL -
Part AEXPERIMENTALThis part will be 3 + 3 dose escalation study of M6620 in combination with gemcitabine as well as gemcitabine and cisplatin in participants with advanced solid tumors.
Part BEXPERIMENTALThis part will be 3 + 3 dose escalation study of M6620 in combination with cisplatin or cisplatin and etoposide in participants with advanced solid tumors.
Part B2EXPERIMENTALThis part will be 3 + 3 dose escalation study of M6620 in combination with irinotecan in participants with advanced solid tumors.
Part C1EXPERIMENTALThis will be the expansion part of the study in which participants with advanced non-small cell lung cancer (NSCLC) will be administered M6620 in combination with gemcitabine.
Part C2EXPERIMENTALThis will be the expansion part of the study in which participants with advanced triple negative breast cancer (TNBC) will be administered M6620 in combination with cisplatin.
Part C3EXPERIMENTALThis will be the expansion part of the study in which participants with platinum-resistant advanced small cell lung cancer (SCLC) will be administered M6620 in combination with cisplatin or carboplatin.

Interventions

NameTypeDescription
BerzosertibDRUGParticipants received Berzosertib at a dose of 105 milligrams per square meter (mg/m\^2 ) intravenously on Day 2 and Day 5 of each 21-day cycle until disease progression or other criteria for study intervention discontinuation are met.
TopotecanDRUGParticipants received Topotecan at a dose of 1.25 mg/m\^2 intravenously on Days 1 through 5 of each 21-day cycle in DL1 and DL2 of safety run-in part and main part until disease progression or other criteria for study intervention discontinuation are met.
[14C]BerzosertibDRUGParticipants received single intravenous infusion of \[14C\]Berzosertib at a dose of 210 milligrams per square meter (mg/m\^2) on Day 1 in Period 1 and stay in clinical research unit (CRU) is required until the discharge criteria are met with a maximum confinement period of 15 days.
M6620DRUGParticipants received 90 milligrams per square meter (mg/m\^2) of M6620, intravenously (IV) on Day 2 of every 3 weeks (Q3W) cycle for a maximum of 6 cycles in combination treatment with carboplatin and avelumab on Day 1. The M6620 dose may be de-escalated to 60 mg/m\^2, or 40 mg/m\^2.
AvelumabDRUGParticipants received IV infusion of avelumab 1600 mg on Day 1 of each Q3W cycle for maximum of 6 cycles in combination treatment with carboplatin and M6620. Thereafter, avelumab 800 mg intravenously on Day 1 of every two weeks as a maintenance mono-therapy until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.
CarboplatinDRUGParticipants received carboplatin area under the concentration-time curve 5 on Day 1 of each Q3W cycle for a maximum of 6 cycles in combination treatment with avelumab and M6620.
CisplatinDRUGCisplatin is a platinum based chemotherapy drug licensed to treat a number of different types of cancer. Cisplatin use is not considered standard practice in Stage A2 \& B, therefore Cisplatin is considered an investigational medicinal product for the purpose of this trial.
CapecitabineDRUGCapecitabine is a chemotherapy drug licensed to treat a number of different types of cancer, it is a noncytotoxic pre-cursor of the cytotoxic 5-fluourouracil. Capecitabine use is not considered standard practice in Stage A2 \& B, therefore Capecitabine is considered an investigational medicinal product for the purpose of this trial.
RadiotherapyRADIATIONStage A1 uses palliative radiotherapy. Stage B uses definitive radiotherapy.
GemcitabineDRUG -
EtoposideDRUG -
IrinotecanDRUG -
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites51

Inclusion Criteria: * Dose level 1 participants with histologically proven advanced solid tumors, for which no effective standard therapy exists, or standard therapy has failed or cannot be tolerated * Dose level 1 participants with Eastern Cooperative Oncology Group Performance Status (ECOG PS) le...

Countries:United StatesBelgiumChinaFranceItalyJapanSpainHungaryUnited Kingdom
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Competitive Landscape -Other Solid Tumors 10 trials (matched to "Advanced Solid Tumor")

Frequently asked questions about M6620

What is M6620?

M6620 is an investigational small molecule developed by Merck KGaA for the treatment of advanced solid tumors, oesophageal adenocarcinoma, and ovarian cancer. It is being studied in Phase 1 clinical development, both as a single agent and in combination with other anticancer therapies, including carboplatin and avelumab.

What is M6620 used for in ovarian cancer?

M6620 has been studied in ovarian cancer in combination with carboplatin and avelumab in patients whose disease is resistant to PARP inhibitors. This combination was evaluated in a Phase Ib/II trial conducted in the United States, Belgium, and the United Kingdom. M6620 remains investigational and is not approved for ovarian cancer.

Who makes M6620?

M6620 is developed by Merck KGaA, which trades over the counter in the United States under the ticker MKGAF. Merck KGaA is the sponsor of the clinical program evaluating M6620 in advanced solid tumors, oesophageal adenocarcinoma, and ovarian cancer.

What phase is M6620 in?

M6620 is in Phase 1 clinical development. It has been evaluated in completed Phase 1 studies, including a first-in-human trial, a study in oesophageal and other cancers, and a combination study in PARP inhibitor-resistant ovarian cancer. M6620 is investigational and has not been approved by the FDA.

What clinical trials is M6620 in?

M6620 has been studied in three completed Phase 1 trials: NCT02157792, a first-in-human study in advanced solid tumors with 200 participants; NCT03641547, testing M6620 plus standard treatment in oesophageal and other cancers; and NCT03704467, combining carboplatin, M6620, and avelumab in PARP inhibitor-resistant ovarian cancer.

What types of cancer has M6620 been studied in?

M6620 has been studied in advanced solid tumors, oesophageal adenocarcinoma including squamous cell carcinoma, and ovarian cancer. The ovarian cancer study focused on patients with PARP inhibitor-resistant disease, while the oesophageal study combined M6620 with standard treatment. All of these trials were Phase 1 and have been completed.