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Metastatic or Locally Advanced Unresectable Solid TumorsPhase 1NCT05396833

Study of Tuvusertib (M1774) in Combination With DNA Damage Response Inhibitor or Immune Checkpoint Inhibitor (DDRiver Solid Tumors 320)

A Phase 1 study testing Tuvusertib, Lartesertib and Avelumab in people with Metastatic or Locally Advanced Unresectable Solid Tumors, run by EMD Serono Research & Development Institute, Inc. at 22 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is an open-label, multicenter, clinical study conducted in multiple parts to establish the safety, tolerability, Pharmacokinetic/Pharmacodynamic (PK/PD) profile, maximum tolerated dose (MTD) combinations (if observed) and recommended dose for expansion (RDE) combination for tuvusertib in combination with… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Tuvusertib, Lartesertib and Avelumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
22 sitesin 5 countries
Study dates
7 Jun 2022to 14 Jul 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Parts A1, A1.1, A1.2, A2, A3, and A2/3: Participants with metastatic or locally advanced unresectable solid tumors refractory to standard therapy or for which no standard therapy is judged appropriate by the Investigator, which may convey clinical benefit, or who cannot tolerate standard of care treatment
  • Parts A1.1 and A1.2: Triple negative breast cancer, epithelial ovarian cancer, castrate resistant prostate cancer, urothelial cancer, endometrial cancer, and colorectal cancer independent of mutation status.
  • Part A2: Participants with advanced prostate cancer whose tumor carries a genetic loss of function (LoF) mutation(s) in the gene ataxia telangiectasia mutated (ATM). No more than 3 prior lines of therapy for castrate resistant disease. Prior therapy must have included a taxane and a novel antiandrogen (example [e.g.] enzalutamide).
  • Part A3: Participants with advanced endometrial cancer whose tumor carries a genetic LoF mutation(s) in the gene AT-rich interaction domain 1A (ARID1A). Prior therapy must have included a platinum agent. Prior therapy must also have included a checkpoint inhibitor if the participant has mismatch repair (MMR)-deficient endometrial cancer. Note for Parts A2/A3: Participants with ATM LoF mutated prostate cancer and ARID1A LoF mutated endometrial cancer should be prioritized to the respective expansion arms instead of being enrolled in Part A1.1. The presence of ATM and ARID1A LoF mutations will be determined according to historic data collected prior to prescreening, generated by an assay with appropriate regulatory status, in either tumor or liquid biopsy. The Sponsor will confirm that mutations certified by historic data fulfil this definition.
  • Participants with eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, with estimated life expectancy of at least 3 months
  • Adequate hematological, hepatic, and renal function as defined in the protocol
  • Other protocol defined inclusion criteria could apply

Who cannot join

  • Participants with any condition, including any uncontrolled disease state other than with metastatic or locally advanced unresectable solid tumors, that in the Investigator's opinion constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation
  • Participants with a known additional malignancy that is progressing and/or requires active treatment
  • Participants with carcinomatous meningitis are excluded regardless of clinical stability
  • Participants with serious gastrointestinal bleeding within 3 months, refractory nausea and vomiting, uncontrolled diarrhea, known malabsorption, significant small bowel resection or gastric bypass surgery, use of feeding tubes, other chronic gastrointestinal disease, and/or other situations that may preclude adequate absorption of oral medications
  • Participants with organ transplantation, including allogeneic stem cell transplant
  • Other protocol defined exclusion criteria could apply

Trial locations and contacts

22 sites in 5 countries.

22 sites in 5 countries

United States8 sites

  • Augusta University - formerly Georgia Regents University

    Augusta, Georgia, 30912

  • Mary Crowley Cancer Research Centers

    Dallas, Texas, 75230

  • University of Texas M. D. Anderson Cancer Center - Partner

    Houston, Texas, 77030

  • The University of Kansas Medical Center Research Institute, Inc.

    Kansas City, Kansas, 66205

  • University of Miami School of Medicine

    Miami, Florida, 33136

  • Carolina Urologic Research Center

    Myrtle Beach, South Carolina, 29572

  • NEXT Oncology

    San Antonio, Texas, 78229

  • Providence Medical Foundation

    Santa Rosa, California, 95403

Other trials in United States

South Korea6 sites

  • Seoul National University Bundang Hospital

    Seongnam-si, 13620

  • Severance Hospital, Yonsei University Health System - Division of Infectious Diseases

    Seoul, 03722

  • Asan Medical Center

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 06351

  • The Catholic University of Korea, Seoul St. Mary's Hospital

    Seoul, 06591

  • Korea University Guro Hospital

    Seoul, 08308

Other trials in South Korea

Spain5 sites

  • Hospital QuironSalud Barcelona - Next Oncology

    Barcelona, 08023

  • Hospital Clinic de Barcelona - Servicio de Oncologia

    Barcelona

  • Centro Integral Oncologico Clara Campal - Unidad de Fase I-Oncologica

    Madrid, 28050

  • Hospital Universitario Quironsalud Madrid - NEXT Oncology

    Madrid, 28223

  • Hospital Universitario Fundacion Jimenez Diaz - START Madrid FJD - Oncology Phase I

    Madrid

Other trials in Spain

Australia2 sites

  • Royal North Shore Hospital

    St Leonards

  • Calvary Mater Newcastle - PARENT

    Waratah

Other trials in Australia

Canada1 site

  • Princess Margaret Cancer Centre

    Toronto, M5G 2C1

Other trials in Canada

About this study

Official title: An Open-label, Multicenter Phase Ib Study of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of the ATR Inhibitor Tuvusertib (M1774) in Combination With DNA Damage Response Inhibitors or Immune Checkpoint Inhibitors in Patients With Metastatic or Locally Advanced Unresectable Solid Tumors (DDRiver Solid Tumors 320)

This is an open-label, multicenter, clinical study conducted in multiple parts to establish the safety, tolerability, Pharmacokinetic/Pharmacodynamic (PK/PD) profile, maximum tolerated dose (MTD) combinations (if observed) and recommended dose for expansion (RDE) combination for tuvusertib in combination with lartesertib (in Part A1), food effect on the PK of lartesertib as monotherapy followed by treatment with tuvusertib in combination with lartesertib in participants with specific tumor types (in Part A1.1), relative bioavailability of a tuvusertib tablet formulation vs capsule formulation followed by treatment with tuvusertib (capsule) in combination with lartesertib in participants with specific tumor types (in Part A1.2), safety/tolerability and early signs of clinical activity of tuvusertib (capsule)and lartesertib in combination in participants with prostate cancer harboring loss of function (LoS) mutation in the gene ATM based on historic data collected prior to prescreening in circulating tumor (ct) DNA (liquid biopsies) or tumor biopsies (in Part A2), safety/tolerability and early signs of clinical activity of tuvusertib and lartesertib in combination in participants with endometrial cancer harboring LoS mutation(s) in the gene ARID1A based on historic data collected prior to prescreening in ctDNA (liquid biopsies) or tumor biopsies (in Part A3), the relative bioavailability of a tuvusertib tablet formulation (TF1, test) compared to a capsule formulation (reference) will also be investigated (in Part A2/A3), and identify a potential set of MTD combinations, and establish the RDE for the combination of tuvusertib and avelumab in participants with metastatic or locally advanced unresectable solid tumors (in Part B1).

Being tested
Tuvusertib, Lartesertib, Avelumab
Keywords
ATR inhibitor, ATM inhibitor, Immunotherapy, Tuvusertib (M1774), Lartesertib (M4076), Avelumab, Metastatic or Locally Advanced Unresectable Solid Tumors, DNA Damage Response Inhibitor, Immune Checkpoint Inhibitor
Medical subject headings
Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TuvusertibDrug

    Also called M1774

    Tuvusertib will be administered orally once daily over a defined period of time in Part A1, A1.1, A1.2, A2, A3, A2/A3, and Part B1 until disease progression, death, discontinuation, or end of study.

  • LartesertibDrug

    Also called M4076

    Lartesertib will be administered orally once daily over a defined period of time in Part A1, A1.1, A1.2, A2, A3, A2/A3, until disease progression, death, discontinuation, or end of study.

  • AvelumabDrug

    Avelumab will be administered by intravenous infusion once a day over a defined period of time in Part B1 until disease progression, death, discontinuation, or end of study.

Study groups in NCT05396833
Study groupRoleWhat they receive
Part A1: Tuvusertib and LartesertibExperimentalNot described
Receives: Drug: Tuvusertib; Drug: Lartesertib
Part A1.1: Tuvusertib and LartesertibExperimentalAssessment of the Effect of Food (Low-fat Meal) on the PK of M4076 Monotherapy Followed by Treatment with M1774 in Combination with M4076
Receives: Drug: Tuvusertib; Drug: Lartesertib
Part A1.2: Tuvusertib and LartesertibExperimentalRelative Bioavailability Assessment of Tuvusertib Tablet (TF1) vs Capsule Followed by Treatment with Tuvusertib in Combination with Lartesertib
Receives: Drug: Tuvusertib; Drug: Lartesertib
Part A2: Tuvusertib and LartesertibExperimentalATM in prostate cancer (Part A2)
Receives: Drug: Tuvusertib; Drug: Lartesertib
Part A3: Tuvusertib and LartesertibExperimentalARID1A in endometrial cancer
Receives: Drug: Tuvusertib; Drug: Lartesertib
Part A2/A3: Tuvusertib and LartesertibExperimentalTablet formulation (TF1, test) compared to a capsule formulation (reference)
Receives: Drug: Tuvusertib; Drug: Lartesertib
Part B1: Tuvusertib and AvelumabExperimentalNot described
Receives: Drug: Tuvusertib; Drug: Avelumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part A1: Number of Participants With Dose-Limiting Toxicities (DLTs) During the DLT Evaluation Period

    Measured: Day 1 up to Day 28

  2. Part A1: Number of Participants With Adverse Events (AEs) and Treatment-Related AEs

    Measured: Baseline up to 18 months

  3. Part B1: Number of Participants with Dose-Limiting Toxicities (DLTs) During the DLT Evaluation Period

    Measured: Day 1 up to Day 28

  4. Part B1: Number of Participants with AEs and Treatment-Related AEs

    Measured: Baseline up to 18 months

  5. Part A1: Change From Baseline in Pharmacodynamic (PD) Biomarker

    The PD biomarker of histone variant will be measured by flow cytometry.

    Measured: Pre-dose up to approximately 1 month

  6. Part B1: Change From Baseline in PD Biomarker

    The PD biomarker of histone variant will be measured by flow cytometry.

    Measured: Pre-dose up to approximately 1 month

  7. Part A1.1: PK Plasma Concentration of Lartesertib Under Fed and Fasted Conditions

    Measured: Day -1 up to Period 1 Day 1

  8. Part A2/A3: Objective Response according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by Investigator

    Measured: Up to 18 months after first dose administration

  9. Part A2/A3: Number of Participants With AEs and Treatment-Related AEs

    Measured: Baseline up to 18 months

  10. Part A1.2: Relative Bioavailability Based on Area Under the Plasma Concentration Curve From Time Zero Extrapolated to Infinity [Frel(AUC0-inf)] of Tuvusertib Test Treatment Compared to Tuvusertib Reference Treatment

    Measured: Day -4 up to Period 1 Day 1

  11. Part A1.2: Relative Bioavailability Based on Area Under the Plasma Concentration Curve From Time Zero to Last Quantifiable Concentration [Frel(AUC0-t)] of Tuvusertib Test Treatment Compared to Tuvusertib Reference Treatment

    Measured: Day -4 up to Period 1 Day 1

  12. Part A1.2: Ratio Maximum Observed Plasma Concentration (Ratio[Cmax]) of Tuvusertib Test Treatment Compared to Tuvusertib Reference Treatment

    Measured: Day -4 up to Period 1 Day 1

  13. Part A2/A3: Relative Bioavailability Based on Area Under the Plasma Concentration Curve From Time Zero Extrapolated to Infinity [Frel(AUC0-inf)] of Tuvusertib Test Treatment Compared to Tuvusertib Reference Treatment

    Measured: Day -4 up to Period 1 Day 1

  14. Part A2/A3: Relative Bioavailability Based on Area Under the Plasma Concentration Curve From Time Zero to Last Quantifiable Concentration [Frel(AUC0-t)] of Tuvusertib Test Treatment Compared to Tuvusertib Reference Treatment

    Measured: Day -4 up to Period 1 Day 1

  15. Part A2/A3: Ratio Maximum Observed Plasma Concentration (Ratio[Cmax]) of Tuvusertib Test Treatment Compared to Tuvusertib Reference Treatment

    Measured: Day -4 up to Period 1 Day 1

Secondary outcomes (12)

  1. Part A1: Pharmacokinetic (PK) Plasma Concentration of Tuvusertib and Lartesertib

    Measured: Pre-dose up to approximately 6 months

  2. Parts A1.2 and B1: Pharmacokinetic (PK) Plasma Concentration of Tuvusertib

    Measured: Pre-dose up to approximately 6 months

  3. Part B1: Pharmacokinetic (PK) Serum Concentration of Avelumab

    Measured: Pre-dose up to approximately 18 months

  4. Part A1 and B1: Number of Participants with Clinically Significant Abnormalities in Digital Electrocardiogram (ECG) Measures

    Measured: Baseline up to 18 months

  5. Part A1 and B1: Objective Response (OR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1

    Measured: Up to 18 months after first dose administration

  6. Part B1: Number of Participants with Any Positive Anti-Drug Antibody (ADA) of Avelumab

    Measured: Baseline up to 18 months

  7. Parts A1.1, A1.2 and A2/3: Number of Participants With AEs and Treatment-Related AEs

    Measured: Baseline up to 18 months

  8. Part A1.1: PK Plasma and Urine Concentration of Lartesertib Under Fed and Fasted Conditions

    Measured: Day -1 up to Period 1 Day 1

  9. Part A2/A3: Time to Reach Maximum Plasma Concentration (tmax) of Tuvusertib

    Measured: Day -4 up to Period 1 Day 1

  10. Part A2/A3: Duration of Response according to RECIST v1.1

    Measured: Up to 18 months after first dose administration

  11. Part A2/A3: Clinical benefit (either OR or stable disease for 6 months or more) according to RECIST v1.1.

    Measured: Up to 18 months after first dose administration

  12. Part A2/A3: Progression Free Survival according to RECIST v1.1 modified according to the Prostate Cancer Working Group 3 (PCWG-3), assessed by Investigator

    Measured: Up to 18 months after first dose administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 May 2022
  2. Study start7 Jun 2022
  3. Primary completion14 Jul 2026
  4. Study completion14 Jul 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
120 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05396833
Sponsor's protocol ID
MS201924_0020
Other IDs
2022-500287-35-00
Status last verified
Sep 2026
First submitted
24 May 2022
Last updated
14 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: IPD will not be shared for Phase I interventional or observational studies. Further information on how to request data can be found on our website bit.ly/IPD21.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tuvusertib, Lartesertib and Avelumab in people with Metastatic or Locally Advanced Unresectable Solid Tumors, run by EMD Serono Research & Development Institute, Inc. at 22 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United States, South Korea, Spain, Australia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A1: Number of Participants With Dose-Limiting Toxicities (DLTs) During the DLT Evaluation Period (time frame: Day 1 up to Day 28). The study lists 15 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05396833.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2026.

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