Clinical trial NCT06421935: M9466 Alone or in Combination in Advanced Solid Tumors (DDriver 501)
Official title: An Open Label, Multicenter, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of the PARP1 Inhibitor M9466 Alone or in Combination in Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Keywords: PARP inhibitor
castration-resistant prostate cancer
ovarian cancer
Abiraterone Acetate
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2024-05-20
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic profile of M9466 with and without tuvusertib or an ARPi and early signs of clinical activity of M9466 with tuvusertib in participants with advanced solid tumors. Study details include: Study/Treatment Duration: Participants will be treated until disease progression, death, discontinuation, or End of Study. Visit Frequency: Every week in the first 2 cycles, followed by every 3 weeks in the subsequent cycles. An End of Treatment Visit and Safety Follow-up/Discontinuation Visit are scheduled after the treatment period.


Eligibility criteria: Inclusion Criteria:

* Module 1 Part A1 and Module 2 Part A1: Locally advanced or metastatic disease that is refractory to standard therapy or for which no standard therapy is judged appropriate by the Investigator
* Eastern Cooperative Oncology Group Performance Status less than or equal to (\<=) 1
* Life expectancy of more than 6 months
* Have adequate hematologic function
* Participants who received chemotherapy, extensive radiotherapy, biological therapy (e.g. antibodies) or investigational agents will have a washout period of 4 weeks (6 weeks for nitrosourea, mitomycin-C) or 5 half-lives whichever is shorter, prior to starting study intervention with M9466 (± tuvusertib)
* Module 3 Part A1:

  * Histologically or pathologically confirmed diagnosis of prostate cancer
  * Metastatic disease documented by positive bone scan or metastatic lesions on CT or MRI
  * Participants with Metastatic Castration-Resistant Prostate Cancer (mCRPC) or metastatic hormone-sensitive prostate cancer (mHSPC) are allowed. For mCRPC, serum testosterone levels ≤ 50 /dL (≤ 1.75 nmol/L).
  * Ongoing ADT with a GnRH agonist or antagonist for participants who have not undergone bilateral orchiectomy must be initiated before first dose and must continue throughout the study.
  * Candidate for treatment with ·abiraterone acetate.
  * Prior anticancer therapy allowed for mHSPC or mCRPC
* Other protocol defined inclusion criteria could apply

Exclusion Criteria:

* Persistence of Adverse Events related to any prior treatments that have not recovered to Grade less than 1 by NCI Common Terminology Criteria for Adverse Events- v5.0 unless AEs are clinically nonsignificant and/or stable on supportive therapy in the opinion of the Investigator (e.g. neuropathy or alopecia)
* Participant has a history of malignancy within 5 years before the date of enrollment (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, benign prostate neoplasm/hypertropia, or malignancy that in the opinion of the Investigator, with concurrence of the Sponsor's Medical Monitor, is considered cured with minimal risk of recurrence within 3 years)
* Participants with known brain metastases, except if clinically controlled, which is defined as individuals with Central Nervous System (CNS) tumors that have been treated, are asymptomatic and who have discontinued steroids (for the treatment of CNS tumors) for more than 28 days
* 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 (including exocrine pancreatic insufficiency requiring pancreatic enzyme replacement therapy), and/or other situations that may preclude adequate absorption of oral medications
* Cerebrovascular accident or stroke
* Module 3 only:

  * Current evidence of any of the following:

    1. Any medical condition that would make prednisone (or equivalent) use contraindicated.
    2. Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone (or equivalent) once daily.
  * History of uncontrolled pituitary or adrenal dysfunction
  * Hypokalemia
* Other protocol defined exclusion criteria could apply

Primary outcomes:
measure: Module 1 Part A1: Number of Participants With Treatment-Emergent Adverse Events (TEAE), and Treatment-related AEs
timeFrame: Time from first treatment up to 30 days after end of study intervention (approximately assessed up to 20 months)
measure: Module 1 Part A1: Number of Participants with Dose Limiting Toxicity (DLT)-like events
timeFrame: Day 1 up to Day 21 of Cycle 1 (each cycle is of 21 days)
measure: Module 2 Part A1: Pharmacokinetic (PK) Plasma Concentrations of M9466
timeFrame: Day 1, Day 8 and Day 15
measure: Module 3 Part A1: Number of Participants With Treatment-Emergent Adverse Events (TEAE), and Treatment-related AEs
timeFrame: Time from first treatment up to 30 days after end of study intervention
measure: Module 3 Part A1: Number of Participants with Dose Limiting Toxicity (DLT)-like Events
timeFrame: Day 1 up to Day 21 of Cycle 1(each cycle is of 21 days)
Secondary outcomes:
measure: Module 1 Part A1: Pharmacokinetic (PK) Plasma Concentrations of M9466 and Tuvusertib
timeFrame: Day 1, Day 8 and Day 15
measure: Module 1 Part A1: Objective Response (OR) According to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 as Assessed by Investigator
timeFrame: Time from first treatment to planned assessment at 12 months
measure: Module 1 Part A1: Effect of M9466 in combination with tuvusertib on QTc interval as determined by Digital ECGs
timeFrame: Time from first treatment to planned assessment at 12 months
measure: Module 2 Part A1: Number of Participants With Treatment-Emergent Adverse Events (TEAE), and Treatment-Related AEs
timeFrame: Time from first treatment up to 30 days after end of study intervention (approximately assessed up to 20 months)
measure: Module 2 Part A1: Number of Participants with Abnormalities in Digital Electrocardiogram (ECG) Measures
timeFrame: Time from first treatment up to 30 days after end of study intervention (approximately assessed up to 20 months)
measure: Module 2 Part A1: Pharmacokinetic (PK) Plasma Concentrations of M9466 and Tuvusertib
timeFrame: Day 1, Day 8 and Day 15
measure: Module 2 Part A1: Relative Changes in Pharmacodynamic Markers In Paired Tumor Biopsies
timeFrame: Day 1, Day 8 and Day 15
measure: Module 3 Part A1: Pharmacokinetic (PK) Plasma Concentrations of M9466 M9466 when administered in combination with AA-P
timeFrame: Day 1, Day 8 and Day 15
Other outcomes:
Locations:
city: New York
country: United States
facility: NEXT Oncology - PARENT
state: New York
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: St Leonards
country: Australia
facility: GenesisCare North Shore (Oncology)
city: Fukuoka-shi
country: Japan
facility: Harasanshin Hospital
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East - Dept of Experimental Therapeutics
city: Koto-ku
country: Japan
facility: Cancer Institute Hospital of JFCR
city: Kumamoto-shi
country: Japan
facility: NHO Kumamoto Medical Center - Dept of Urology
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System - Division of Infectious Diseases
city: Barcelona
country: Spain
facility: Hospital HM Nou Delfos - START Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron - Oncology Dept.
city: Barcelona
country: Spain
facility: ICO l'Hospitalet - Hospital Duran i Reynals - Servicio de Oncologia
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal - Unidad de Fase I-Oncologica
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre - Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz - START Madrid FJD - Oncology Phase I
city: Pozuelo de Alarcon
country: Spain
facility: NEXT Madrid - Hospital Universitario Quironsalud Madrid
Study officials:
affiliation: EMD Serono Research & Development Institute, Inc.
name: Medical Responsible
role: STUDY_DIRECTOR
References: