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Participants will receive single oral dose of M1774 containing a \[14C\]M1774 microtracer solution on day 1 of period 1 under fasted conditions.

M1774 [14C]M1774 microtracer

Participants will receive a single oral dose of M1774 on Day 1 of Period 1, and daily single oral dose of M1774 for 2 weeks in 21 days cycle of Period 2.

M1774

Communication Center

Medical Responsible

This is a single sequence 2-period open label study in participants with advanced solid tumors. The purpose of Period 1 of this study is to assess the mass balance to determine drug-related entities present in circulation and excreta and provide a comprehensive understanding of biotransformation pathways and clearance mechanisms in participants with advanced solid tumors. Thereafter, participants may enter an optional extension phase (Period 2) where participants will receive M1774 until disease progression or other criteria for study intervention discontinuation are met.

M1774 Human Mass Balance Study (DDRIVER Solid Tumors 303)

Phase 1 Study to Evaluate the Mass Balance, Pharmacokinetics, Metabolism and Excretion of M1774 Containing Microtracer [14C] M1774 in Participants With Advanced Solid Tumors (DDRIVER Solid Tumors 303)

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 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.

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

Niraparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Tuvusertib (M1774)

Lartesertib (M4076)

US Medical Information

Please Contact U.S. Medical Information

Please Contact the Communication Center

The purpose of this study is to measure the effect and safety of treatment with tuvusertib combined with either niraparib or lartesertib in participants with epithelial ovarian cancer. The participants will previously have progressed while treated with a poly ADP ribose polymerase (PARP) inhibitor. The primary objective of the study is to assess the effect of the treatment in terms of overall response, i.e. whether the tumor disappears, shrinks, remains unchanged, or gets worse.

Tuvusertib Combined With Niraparib or Lartesertib in Participants With Epithelial Ovarian Cancer (DDRiver EOC 302)

An Open-label, Multicenter, Randomized Phase 2 Study of the ATR Inhibitor Tuvusertib in Combination With the PARP Inhibitor Niraparib or the ATM Inhibitor Lartesertib in Participants With BRCA Mutant and/or Homologous Recombination deﬁciency (HRD)-Positive Epithelial Ovarian Cancer That Progressed on Prior PARP Inhibitor Therapy (DDRiver EOC 302)

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 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

Merck KGaA, Darmstadt, Germany

EMD Serono Research & Development Institute, Inc.

Participants will initially receive Tuvusertib (M1774) once daily under fasting conditions. Additional schedules may be evaluated if needed.

Participants in the food effect assessment will receive Tuvusertib (M1774) at the dose and schedule determined as recommended dose for expansion (RDE) in Part A1. A single dose of Tuvusertib (M1774) will be administered on Day -7 under a fed (low-fat meal) or fasted condition, followed by a 1-week washout period. After completion of the scheduled food effect assessments, participants will follow the same schedule as participants in Part A1.

Part A3 is an expansion of Part A1 where Tuvusertib (M1774) will be administered as a single agent at the RDE established in Part A1. Participants with defined loss-of-function mutation in ARID1A, ATRX and/or DAXX, and ATM will be enrolled.

B1a: Participants with baseline body weight less than (\<) 77 kilogram (kg) or platelets \<150,000 cubic per millimeter (mm\^3) will receive Niraparib once daily combined with different doses of Tuvusertib (M1774).

B1b: Participants with baseline body weight greater than or equal to (\>=) 77 kg and or platelets \>= 150,000 mm\^3 will receive Niraparib once daily combined with different doses of Tuvusertib (M1774) and schedule determined as recommended dose for expansion (RDE) in Part B1a.

Starting at global RDE from Part A1, in Japan. Participants will initially receive Tuvusertib (M1774) once daily under fasting conditions. Additional schedules may be evaluated if needed.

Starting at global RDE from Part A1, in China. Participants will initially receive Tuvusertib (M1774) once daily under fasting conditions. Additional schedules may be evaluated if needed.

M1774 will be administered orally throughout the study.

Niraparib will be administered orally throughout the study.

This is an open-label, Phase I, first-in-human (FIH) multicenter, clinical study conducted in multiple parts to establish the safety, tolerability and pharmacokinetic/pharmacodynamic (PK/PD) profile (with and without food) and early signs of efficacy of Tuvuseritib (M1774) as monotherapy and in combination with the poly (ADP-ribose) polymerase (PARP) inhibitor niraparib.

Tuvusertib (M1774) in Participants With Metastatic or Locally Advanced Unresectable Solid Tumors (DDRiver Solid Tumors 301)

An Open-label, Multicenter Trial of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of Tuvusertib (M1774) in Participants With Metastatic or Locally Advanced Unresectable Solid Tumors (DDRiver Solid Tumors 301)

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

Participants with a clinical benefit, defined as an objective response or stable disease for at least 6 months, as determined by the Investigator through the use of RECIST version 1.1.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
M1774 Human Mass Balance Study (DDRIVER Solid Tumors 303)	NCT06308263	Solid Tumor	M1774 [14C]M177... M1774	18 Years -	Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Tuvusertib Combined With Niraparib or Lartesertib in Participants With Epithelial Ovarian Cancer (DDRiver EOC 302)	NCT06433219	Ovarian Cancer	Tuvusertib (M17... Niraparib Lartesertib (M4...	18 Years -	EMD Serono
Tuvusertib (M1774) in Participants With Metastatic or Locally Advanced Unresectable Solid Tumors (DDRiver Solid Tumors 301)	NCT04170153	Metastatic or L...	M1774 Niraparib	18 Years -	EMD Serono

Spots Global Cancer Trial Database for tuvusertib (m1774)