Clinical trial • Phase II • Oncology

TUVUSERTIB for Epithelial ovarian cancer

Phase II trial of TUVUSERTIB for Epithelial ovarian cancer.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Epithelial ovarian cancer
Trial Stage
Phase II
Drug Modality
Small molecule
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
13-06-2024
First CTIS Authorization Date
30-09-2024

Trial design

Randomised, open-label, arms include combinations vs monotherapy: part a - arm 1: tuvusertib + niraparib (both oral); arm 2: tuvusertib + lartesertib (both oral). part b - arm 1: selected combination (tuvusertib + niraparib or tuvusertib + lartesertib) dosing regimen 1 (oral); arm 2: selected combination dosing regimen 2 (oral, lower dose than in part a); arm 3: tuvusertib monotherapy (oral). dose amounts and schedules not specified in the available summary.-controlled, adaptive Phase II trial in Germany, Poland, Belgium and others.

Randomised
Yes
Open Label
Yes
Comparator
Arms include combinations vs monotherapy: Part A - Arm 1: tuvusertib + niraparib (both oral); Arm 2: tuvusertib + lartesertib (both oral). Part B - Arm 1: selected combination (tuvusertib + niraparib or tuvusertib + lartesertib) dosing regimen 1 (oral); Arm 2: selected combination dosing regimen 2 (oral, lower dose than in Part A); Arm 3: tuvusertib monotherapy (oral). Dose amounts and schedules not specified in the available summary.
Adaptive
True, Part A is used to assess efficacy and safety of two combinations to support selection of the best combination for Part B; Part B evaluates two dose levels of the selected combination and monotherapy to inform RP2D selection (adaptive selection of combination and dose levels).
Biomarker Stratified
True, BRCA1/BRCA2 mutation status and homologous recombination deficiency (HRD) status (participants selected/stratified by BRCA mutation and/or HRD-positive tumors).
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
31

Eligibility

Recruits 31 Vulnerable population selected. Informed consent is handled via country-specific subject information and informed consent forms and eConsent materials (multiple language versions and country-specific ICFs are provided). Optional consents for future research and pharmacogenetic research are included. No specific assent procedures for minors are described in the available documents..

Vulnerable Population
Vulnerable population selected. Informed consent is handled via country-specific subject information and informed consent forms and eConsent materials (multiple language versions and country-specific ICFs are provided). Optional consents for future research and pharmacogenetic research are included. No specific assent procedures for minors are described in the available documents.

Inclusion criteria

  • {"criterion_text":"- Histologically or cytologically confirmed high grade serous or high grade endometrioid ovarian, primary peritoneal, and/or fallopian tube cancer that is recurrent.\n- Participants whose tumor carries germline or somatic deleterious or suspected deleterious mutations in the genes BRCA1 (BReast CAncer gene 1) and BRCA2 (BReast CAncer gene 2), and/or tumors with positive HRD status. The presence of any of these mutations and/or the homologous recombination deficiency (HRD) status will be determined according to routinely used local standard of care tests. Results must be available before screening.\n- Radiologically confirmed/documented disease progression while on Poly (ADP-ribose) polymerase (PARP) inhibitors therapy in either first or second-line maintenance setting (only 1 line of PARPi maintenance is allowed with or without bevacizumab). Note: Documentation of disease progression must be within 28 days of last PARPi dose taken. Surgical salvage intervention and/or focal ablative therapies are allowed, (further disease progression after these interventions must be documented), AND Clinically benefited from PARPi maintenance prior to documented progression, as defined by at least 6 months of treatment duration with no progressive disease observed, AND either, Progression on first-line maintenance PARPi: Participants are allowed maximum 1 additional line of platinum-based chemotherapy before study entry. (note: treatment-free interval on platinum rechallenge must be >6 months, with documented disease progression prior to study entry). OR Progression on second-line maintenance PARPi: Participants are not allowed any additional systemic anticancer treatments before study entry (i.e. PARPi is the last treatment before study entry)\n- Intolerant to standard of care treatment options or refused standard of care treatment or the participant’s treating physician considers that the lack of standard of care treatment is not detrimental for the participant.\n- Measurable disease per RECIST v1.1, as assessed by Investigator.\n- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a life expectancy of at least 6 months.\n- Other Protocol defined inclusion criteria."}

Exclusion criteria

  • {"criterion_text":"- Primary platinum-refractory disease defined as disease progression during primary platinum-based chemotherapy or platinum-resistant disease defined as disease progression within 6 months of the platinum administration in either the first or second-line setting\n- History of additional malignancy within 3 years before the date of enrollment.\n- Known brain metastases, unless clinically stable, i.e. without evidence of progression by imaging for at least 4 weeks prior to the first dose of study intervention, no evidence of new brain metastases, and on a stable or decreasing dose of ≤ 10 mg of prednisone (or equivalent) or without corticosteroids for at least 14 days prior to study intervention administration.\n- Active and/or uncontrolled infection\n- History of known hypersensitivity to the active substances or to any excipients (e.g. polysorbate 80) of the study interventions.\n- Organ transplantation, including allogenic stem cell transplant.\n- Patients with history of drug-induced severe cutaneous adverse reaction (SCAR; including but not limited to Stevens-Johnson syndrome/toxic epidermal necrolysis [SJS/TEN], or drug reaction with eosinophilia and systemic symptoms [DRESS]), or dose-limiting immune-mediated reactions related to skin.\n- Other Protocol defined exclusion criteria."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Part A and Part B: Confirmed Objective Response (OR) According to RECIST v1.1 as Assessed by Investigator","definition_or_measurement_approach":"Objective Response (OR) confirmed according to RECIST v1.1, assessed by the Investigator."}
  • {"endpoint_text":"- Part A and Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAE), Serious TEAEs and Related TEAEs","definition_or_measurement_approach":"Counting and categorisation of Treatment-Emergent Adverse Events (TEAEs), serious TEAEs and TEAEs considered related to study treatment."}

Secondary endpoints

  • {"endpoint_text":"- Part A and Part B: Duration of Response (DoR) According to RECIST 1.1 as Assessed by the Investigator","definition_or_measurement_approach":"Duration of Response measured per RECIST v1.1 as assessed by Investigator."}
  • {"endpoint_text":"- Part A and Part B: Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by the Investigator","definition_or_measurement_approach":"Progression-Free Survival measured per RECIST v1.1 as assessed by Investigator."}
  • {"endpoint_text":"- Part B: Overall Survival","definition_or_measurement_approach":"Overall Survival measured as time from randomization/enrolment to death from any cause."}

Recruitment

Digital Remote Recruitment
True, eConsent, ePRO and TeleVisits are used (Medable platform support numbers, eConsent screenshots and instructions for eConsent/ePRO/TeleVisits are provided in country-specific materials).
Planned Sample Size
31
Recruitment Window Months
37
Consent Approach
Informed consent obtained via country-specific informed consent forms (multiple language versions) and eConsent processes; subject information materials and optional ICFs (e.g. optional pharmacogenetic and future research consents) are provided. Materials and eConsent instructions are available in multiple languages (examples include DE, EN, FR, NL, PL, ES, IT, DK). Consent is provided by the participant; no child assent procedures are described in the available documents.

Methods

  • Site-based recruitment via participating oncology clinics and hospitals (country-specific trial sites listed per country).
  • Printed materials: patient brochures, flyers, posters and patient study guides (country- and language-specific versions: DE, EN, FR, NL, PL, ES, IT, DK, BE versions indicated in recruitment documents).
  • Digital/remote support and eConsent: eConsent, ePRO and TeleVisits instructions (Medable platform support numbers and eConsent screenshots referenced).
  • Participant materials: patient ID/emergency cards, visit reminder cards, thank you cards, and participant diaries.

Geography

Total Number Of Sites
57
Total Number Of Participants
99

Germany

Earliest CTIS Part Ii Submission Date
13-09-2024
Latest Decision Or Authorization Date
05-08-2025
Processing Time Days
326
Number Of Sites
9
Number Of Participants
8

Sites

Site Name
KEM I Evang. Kliniken Essen-Mitte gGmbH
Department Name
Gynecology
Contact Person Name
Philipp Harter
Site Name
Universitaet Leipzig
Department Name
Gynecology
Contact Person Name
Bahriye Aktas
Site Name
Technische Universitaet Dresden
Department Name
Gynecology
Contact Person Name
Pauline Wimberger
Site Name
Universitaet Muenster
Department Name
Gynecology
Contact Person Name
Ralf Witteler
Contact Person Email
ralf.witteler@ukmuenster.de
Site Name
Universitaetsklinikum Schleswig-Holstein AöR
Department Name
Gynecology
Contact Person Name
Marion Tina Van Mackelenbergh
Site Name
Universitaetsklinikum Bonn AöR
Department Name
Gynecology
Contact Person Name
Alexander Mustea
Contact Person Email
gynaekologie@ukbonn.de
Site Name
Universitaetsklinikum Regensburg AöR
Department Name
Gynecology
Contact Person Name
Stephan Seitz
Contact Person Email
sseitz@csj.de
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Gynecology
Contact Person Name
Jalid Sehouli
Contact Person Email
jalid.sehouli@charite.de
Site Name
Universitaetsklinikum Schleswig-Holstein AöR (Kiel) - duplicate listing may exist
Department Name
Gynecology
Contact Person Name
Marion Tina Van Mackelenbergh

Poland

Earliest CTIS Part Ii Submission Date
05-07-2024
Latest Decision Or Authorization Date
11-08-2025
Processing Time Days
402
Number Of Sites
8
Number Of Participants
7

Sites

Site Name
Centrum Onkologii Im. Prof. Franciszka Lukaszczyka W Bydgoszczy
Department Name
Ambulatorium Chemioterapii I
Contact Person Name
Bogdan Zurawski
Contact Person Email
zurawskib@co.bydgoszcz.pl
Site Name
Jagiellońskie Centrum Innowacji Sp. z o.o.
Department Name
Centrum Badan Klinicznych JCI
Contact Person Name
Pawel Blecharz
Contact Person Email
pawel.blecharz@interia.pl
Site Name
Szpitale Pomorskie Sp. z o.o.
Department Name
Szpital Morski im. PCK, Oddział Onkologii Klinicznej - Leczenie „Jednego Dnia”
Contact Person Name
Joanna Pikiel
Contact Person Email
joanna.pikiel@post.pl
Site Name
Instytut Msf Sp. z o.o.
Contact Person Name
Ewa Kalinka
Contact Person Email
ewakalinka@wp.pl
Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Department Name
Klinika Ginekologii Onkologicznej
Contact Person Name
Mariusz Bidziński
Contact Person Email
bidzinski.m@gmail.com
Site Name
Wojewodzkie Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M.Kopernika W Lodzi
Department Name
Oddział Chemioterapii Nowotworów z Pododdziałem Chemioterapii Jednego Dnia
Contact Person Name
Joanna Połowinczak-Przybyłek
Site Name
Europejskie Centrum Zdrowia Otwock Sp. z o.o.
Department Name
Szpital im. Fryderyka Chopina, Oddział Onkologii Klinicznej
Contact Person Name
Cezary Szczylik
Contact Person Email
cezary.szczylik@ecz-otwock.pl
Site Name
Medicover Integrated Clinical Services Sp. z o.o.
Department Name
MICS Centrum Medyczne Toruń
Contact Person Name
Justyna Wietrzynska
Contact Person Email
j.wietrzynska@naszlekarz.pl

Belgium

Earliest CTIS Part Ii Submission Date
06-09-2024
Latest Decision Or Authorization Date
05-08-2025
Processing Time Days
333
Number Of Sites
3
Number Of Participants
2

Sites

Site Name
Centre hospitalier universitaire de Liege
Department Name
Oncology
Contact Person Name
Christine Gennigens
Site Name
Cliniques Universitaires Saint-Luc
Department Name
Medical Oncology
Contact Person Name
Jean-François Baurain
Site Name
UZ Leuven
Department Name
Gynaecologic Oncology
Contact Person Name
Els Van Nieuwenhuysen

Netherlands

Earliest CTIS Part Ii Submission Date
24-09-2024
Latest Decision Or Authorization Date
05-08-2025
Processing Time Days
315
Number Of Sites
1
Number Of Participants
1

Sites

Site Name
Catharina Ziekenhuis Stichting
Department Name
Oncology
Contact Person Name
Annemarie Thijs

France

Earliest CTIS Part Ii Submission Date
06-09-2024
Latest Decision Or Authorization Date
28-01-2026
Processing Time Days
509
Number Of Sites
16
Number Of Participants
16

Sites

Site Name
Assistance Publique Hopitaux De Paris
Department Name
Medical Oncology
Contact Person Name
Djamel Ghebriou
Contact Person Email
djamel.ghebriou@aphp.fr
Site Name
Groupe Hospitalier Diaconesses Croix Saint Simon
Department Name
Medical Oncology
Contact Person Name
Frédéric Selle
Contact Person Email
fselle@hopital-dcss.org
Site Name
Institut De Cancerologie Strasbourg Europe
Department Name
Medical Oncology
Contact Person Name
Lauriane Eberst
Contact Person Email
l.eberst@icans.eu
Site Name
Centre Francois Baclesse
Department Name
Oncology
Contact Person Name
Florence Joly
Contact Person Email
f.joly@baclesse.unicancer.fr
Site Name
Assistance Publique Hopitaux De Paris (Paris Cedex 15)
Department Name
Medical Oncology
Contact Person Name
Jacques Medioni
Contact Person Email
jacques.medioni@aphp.fr
Site Name
Centre Leon Berard
Department Name
Medical Oncology
Contact Person Name
Isabelle Ray-Coquard
Site Name
Groupe Hospitalier Saint Vincent
Department Name
Oncology
Contact Person Name
Youssef Tazi
Contact Person Email
ytazi@solcrr.org
Site Name
Institut Gustave Roussy
Department Name
Medical Oncology
Contact Person Name
Patricia Pautier
Site Name
Clinique Victor Hugo (Centre De Cancerologie De La Sarthe)
Department Name
Oncology - Radiotherapy
Contact Person Name
Sophie Roche
Contact Person Email
essaisroche@ilcgroupe.fr
Site Name
Hospices Civils De Lyon
Department Name
Medical Oncology
Contact Person Name
Benoit You
Contact Person Email
benoit.you@chu-lyon.fr
Site Name
Assistance Publique Hopitaux De Paris (27 Rue Du Faubourg Saint Jacques)
Department Name
Oncology
Contact Person Name
Jerome Alexandre
Contact Person Email
jerome.alexandre@aphp.fr
Site Name
Centre Oscar Lambret
Department Name
Cervico-facial and thoracis onclogy and gynaecology
Contact Person Name
Cyril Abdeddaim
Contact Person Email
c-abdeddaim@o-lambret.fr
Site Name
Institut De Cancerologie De L Ouest
Department Name
Medical Oncology
Contact Person Name
Dominique Berton
Site Name
GIE Groupe hospitalier Paris Saint-Joseph/Vinci
Department Name
Medical Oncology
Contact Person Name
Nicolas Delanoy
Contact Person Email
ndelanoy@ghpsj.fr
Site Name
Institut De Cancerologie De L Ouest (Angers)
Department Name
Oncology
Contact Person Name
Paule Augereau
Site Name
Other authorised French site (listed)

Italy

Earliest CTIS Part Ii Submission Date
28-08-2024
Latest Decision Or Authorization Date
20-04-2026
Processing Time Days
600
Number Of Sites
7
Number Of Participants
44

Sites

Site Name
Azienda Ospedaliera Per L'Emergenza Cannizzaro
Department Name
UOC Oncologia Medica
Contact Person Name
Giuseppa Scandurra
Contact Person Email
giusy.scandurra@gmail.com
Site Name
Istituto Europeo Di Oncologia S.r.l.
Department Name
Unità Ginecologia Oncologica Medica
Contact Person Name
Nicoletta Colombo
Contact Person Email
nicoletta.colombo@ieo.it
Site Name
IRCCS Istituto Nazionale Tumori Fondazione Pascale
Department Name
Urologic oncology - gynecological oncology
Contact Person Name
Sabrina Chiara Cecere
Contact Person Email
s.cecere@istitutotumori.na.it
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
UOC Ostetricia e ginecologia
Contact Person Name
Vanda Salutari
Site Name
Istituto Oncologico Veneto
Department Name
Oncologia Medica 2
Contact Person Name
Valentina Guarneri
Contact Person Email
valentina.guarneri@unipd.it
Site Name
I.F.O. Istituti Fisioterapici Ospitalieri
Department Name
UOC Oncologia Medica A
Contact Person Name
Antonella Savarese
Contact Person Email
antonella.savarese@ifo.it
Site Name
Humanitas Mirasole S.p.A.
Department Name
U.O. di Oncologia Medica ed Ematologia
Contact Person Name
Domenica Lorusso
Contact Person Email
domenica.lorusso@hunimed.eu

Spain

Earliest CTIS Part Ii Submission Date
06-09-2024
Latest Decision Or Authorization Date
22-04-2026
Processing Time Days
593
Number Of Sites
10
Number Of Participants
12

Sites

Site Name
Institut Catala D'oncologia
Department Name
Oncology
Contact Person Name
Marta Gil Martin
Contact Person Email
mgilmartin@iconcologia.net
Site Name
Hospital Universitari De Girona Doctor Josep Trueta
Department Name
Medical Oncology
Contact Person Name
Pilar Barretina Ginesta
Contact Person Email
mpbarretina@iconcologia.net
Site Name
Hospital Germans Trias I Pujol
Department Name
Oncology
Contact Person Name
Pau Guillén Sentís
Contact Person Email
pguillens@iconcologia.net
Site Name
Clinica Universidad De Navarra (Pamplona)
Department Name
Oncology
Principal Investigator Name
Antonio Gonzalez Martin
Principal Investigator Email
agonzalezma@unav.es
Contact Person Name
Antonio Gonzalez Martin
Contact Person Email
agonzalezma@unav.es
Site Name
Hospital Universitario 12 De Octubre
Department Name
Oncology
Principal Investigator Name
Luis Manuel Manso Sanchez
Principal Investigator Email
luismansosanchez@gmail.com
Contact Person Name
Luis Manuel Manso Sanchez
Contact Person Email
luismansosanchez@gmail.com
Site Name
Hospital Universitario Regional De Malaga
Department Name
Medical Oncology
Principal Investigator Name
David Fernandez Garay
Principal Investigator Email
estudios.clinicos@ibima.eu
Contact Person Name
David Fernandez Garay
Contact Person Email
estudios.clinicos@ibima.eu
Site Name
Hospital Universitari Vall D Hebron
Department Name
Oncology
Principal Investigator Name
Ana Oaknin Benzaquen
Principal Investigator Email
aoaknin@vhio.net
Contact Person Name
Ana Oaknin Benzaquen
Contact Person Email
aoaknin@vhio.net
Site Name
Hospital Clinic De Barcelona
Department Name
Oncology
Principal Investigator Name
Lydia Gaba Garcia
Principal Investigator Email
lgaba@clinic.cat
Contact Person Name
Lydia Gaba Garcia
Contact Person Email
lgaba@clinic.cat
Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Oncology
Principal Investigator Name
Eva Maria Guerra Alia
Principal Investigator Email
eva_m_guerra@hotmail.com
Contact Person Name
Eva Maria Guerra Alia
Contact Person Email
eva_m_guerra@hotmail.com
Site Name
Clinica Universidad De Navarra (Madrid)
Department Name
Oncology
Principal Investigator Name
Antonio Gonzalez Martin
Principal Investigator Email
agonzalezma@unav.es
Contact Person Name
Antonio Gonzalez Martin
Contact Person Email
agonzalezma@unav.es

Denmark

Earliest CTIS Part Ii Submission Date
09-09-2024
Latest Decision Or Authorization Date
13-04-2026
Processing Time Days
581
Number Of Sites
3
Number Of Participants
9

Sites

Site Name
Aalborg University Hospital
Department Name
Onkologisk Afdeling, Klinisk Forskningsenhed
Principal Investigator Name
Charlotte Haslund
Principal Investigator Email
cah@rn.dk
Contact Person Name
Charlotte Haslund
Contact Person Email
cah@rn.dk
Site Name
Rigshospitalet
Department Name
Department of Clinical Oncology
Principal Investigator Name
Trine Jakobi Nøttrup
Principal Investigator Email
trine.jakobi.noettrup@regionh.dk
Contact Person Name
Trine Jakobi Nøttrup
Site Name
Region Sjaelland
Department Name
Clinical Oncology
Principal Investigator Name
Zaza Ujmajuridze
Principal Investigator Email
zu@regionsjaelland.dk
Contact Person Name
Zaza Ujmajuridze
Contact Person Email
zu@regionsjaelland.dk

Sponsor

Primary sponsor

Full Name
Merck Healthcare KGaA
Organisation Type
Pharmaceutical company
Country Of Registered Address
Germany

Contract research organisations

Name
IQVIA Limited
Responsibilities
Multiple sponsor duties including code 15 (Alliance CRO) and other operational support (codes 1,10,11,12,3,6,7,8) as listed in sponsor duties.
Name
Iqvia Laboratories Limited
Responsibilities
Sponsor duties code 4 (as listed).

Third parties

  • {"country":"United States","full_name":"Tempus Labs Inc.","duties_or_roles":"4","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"Drug Supply and Distribution","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Iqvia Laboratories Limited","duties_or_roles":"4","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Myriad Genetics Inc.","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"1,10,11,12,15 (Alliance CRO),3,6,7,8, (multiple sponsor duties codes; includes 'Alliance CRO')","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
M1774
Active Substance
TUVUSERTIB
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Investigational Product Name
M4076
Active Substance
8-(1,3-DIMETHYLPYRAZOL-4-YL)-1-(3-FLUORO-5-METHOXYPYRIDIN-4-YL)-7-METHOXY-3-METHYLIMIDAZO[4,5-C]QUINOLIN-2-ONE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Investigational Product Name
Zejula 100 mg film-coated tablets
Active Substance
NIRAPARIB TOSILATE MONOHYDRATE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Marketing authorisation (EU) - EU/1/17/1235/004
Orphan Designation
Yes
Combination Treatment
Yes

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