C61 Malignant neoplasm of prostate Malignant neoplasm of prostate
Conditions
Interventions
MK-2400 (Ifinatamab deruxtecan): Injection, powder, lyophilized, for solution, 100 mg, participants will be administered, at the dose of 12 mg/kg by intravenous infusion, starting at Cycle 1 Day 1 and
Sponsors
Merck Sharp & Dohme LLC., (una subsidiaria de Merck & Co. Inc.)
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Type of Participant and Disease Characteristics: Has histologically- or cytologically-confirmed (if acceptable according to local health authority regulations) adenocarcinoma of the prostate without small cell histology. Diagnosis must be supported in a pathology report and confirmed by the investigator. Has prostate cancer progression while on ADT (or post bilateral orchiectomy) within 6 months prior to Screening, as determined by the investigator, by means of one or more of the following: a. Clinical disease progression (per investigator judgment) and with PSA progression using local laboratory values as defined by a minimum of 2 consecutive rising PSA levels with an interval of =1 week between each assessment where the PSA value at Screening should be =1 ng/mL – See Section 8.2.2 – Prostate-specific Antigen Assessment for further details. Note: A PSA level obtained during the Screening Period can count as the confirmatory second rising PSA. b. Radiographic disease progression in soft tissue based on RECIST 1.1 criteria. c. Radiographic disease progression in bone based on PCWG3, defined as the appearance of 2 or more new bone lesions on bone scan. Has progression under the following conditions if the participant received first generation antiandrogen therapy prior to enrollment: a. Evidence of progression >4 weeks since last flutamide treatment. b. Evidence of progression >6 weeks since last bicalutamide or nilutamide treatment. Has current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue disease by CT/MRI. Has received prior treatment with 1 or 2 ARPI(s) (eg, abiraterone acetate, enzalutamide, apalutamide, or darolutamide) for nmHSPC, mHSPC, nmCRPC, or mCRPC and progressed during or after at least 8 weeks of treatment (at least 14 weeks of treatment for participants with bone progression). Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<1.7 nM). If the participant is currently being treated with luteinizing hormone-releasing hormone agonists or antagonists (participants who have not undergone a bilateral orchiectomy), this therapy must have been initiated at least 4 weeks prior to randomization and treatment must be continued throughout the study. Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses for =4 weeks prior to randomization. Has had prior treatment with PARPi if indicated by local approved regimen or were deemed ineligible to receive treatment by the investigator. Demographics: Is at least 18 years of age at the time of providing the informed consent. If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is: - I-DXd: 150 days - Docetaxel: 120 days • Refrains from donating sperm • PLUS either: • Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR • Uses contraception as detailed below unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview) as detailed below: - Uses a pen
Exclusion criteria
Exclusion criteria: Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Medical Conditions: Has a gastrointestinal disorder affecting absorption (eg, gastrectomy or active peptic ulcer disease within the last 3 months). Is unable to swallow tablets/capsules. Clinically significant corneal disease. History of (non-infectious) ILD/pneumonitis that required steroids or has current ILD/pneumonitis and/or suspected ILD/pneumonitis that cannot be ruled out by standard diagnostic assessments at Screening. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the study enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion, etc), any autoimmune, connective tissue, or inflammatory disorders with potential pulmonary involvement (eg, rheumatoid arthritis, Sjogren’s syndrome, sarcoidosis, etc), prior pneumonectomy, or requirement for supplemental oxygen. History of hypersensitivity, intolerance, or contraindications to taxanes, prednisone/prednisone acetate/prednisolone/prednisolone acetate, or any of the investigational drug substances, inactive ingredients in the drug product (polysorbate 80, polysorbate 20), or severe hypersensitivity reactions to other monoclonal antibodies. Has CTCAE V5.0 Grade =3 peripheral neuropathy, except when due to trauma. Uncontrolled or significant cardiovascular disease, including: a. QT interval corrected with Fridericia’s formula (QTcF) interval >470 ms based on average of the screening triplicate 12-lead ECG determinations. b. Diagnosed or suspected long QT syndrome or known family history of long QT syndrome. c. History of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes. d. Bradycardia of less than 50 bpm unless the participant has a pacemaker. e. History of second- or third-degree heart block. Candidates with a history of heart block may be eligible if they currently have a pacemaker and have no history of fainting or clinically relevant arrhythmia with the pacemaker. f. Acute myocardial infarction within 6 months prior to Screening. g. Coronary heart disease that is symptomatic or uncontrolled angina pectoris within 6 months prior to screening. h. History of stroke or transient ischemic attack or another arterial thromboembolic event within 6 months prior to screening. i. Symptomatic CHF defined as NYHA Class II to IV. j. Coronary/peripheral artery bypass graft or any coronary/peripheral angioplasty within 6 months prior to Screening. k. Any of following at the Screening Visit: -Hypotension: systolic BP <86 mm Hg, or -Uncontrolled hypertension: systolic BP =160 mm Hg or diastolic BP =90 mm Hg, in 2 of 3 recordings with optimized antihypertensive therapy. l. Complete left or right bundle branch block. m. LVEF <50% by either an ECHO or a MUGA scan. n. A resting ECG indicating uncontrolled, potentially reversible cardiac conditions as judged by the investigator. Prior/Concomitant Therapy: Has received prior treatment with a taxane-based chemotherapy agent for mCRPC Note: Docetaxel for HSPC is allowed provided there w
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Elapsed time measurement. Testing: stratified log-rank test. Estimation: Stratified Cox model with Efron’s tie handling method. NAME OF THE RESULT: Radiographic Progression-Free Survival (rPFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Time from randomization to the first documented disease progression per PCWG-modified RECIST 1.1 by BICR or death due to any cause, whichever occurs first.;Elapsed time measurement. Testing: stratified log-rank test. Estimation: Stratified Cox model with Efron’s tie handling method. NAME OF THE RESULT: Overall Survival (OS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Time from randomization to death due to any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| Elapsed time measurement. Testing: stratified log-rank test. Estimation: Stratified Cox model with Efron’s tie handling method. NAME OF THE RESULT: Overall Survival (OS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Time from randomization to death due to any cause.;Elapsed time measurement. Testing: stratified log-rank test. Estimation: Stratified Cox model with Efron’s tie handling method. NAME OF THE RESULT: Radiographic Progression-Free Survival (rPFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Time from randomization to the first documented disease progression per PCWG-modified RECIST 1.1 by BICR or death due to any cause, whichever occurs first.;Elapsed time measurement. NAME OF THE RESULT: Time to First Subsequent Therapy (TFST) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Time from randomization to initiation of the first subsequent anticancer therapy or death, whichever occurs first.;Confirmed complete response (CR) or partial response (PR) per PCWG-modified RECIST 1.1 as assessed by BICR. NAME OF THE RESULT: Objective Response (OR) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Throughout the study.;Elapsed time measurement. NAME OF THE RESULT: Duration of Response (DOR) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Time from the first documented evidence of CR or PR until disease progression per PCWG-modified RECIST 1.1 as assessed by BICR or death due to any cause, whichever occurs first.;Elapsed time measurement. NAME OF THE RESULT: Time to Pain Progression (TTPP) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Time from randomization to pain progression based on the BPI-SF Item 3 “worst pain in 24 hours” | — |
Countries
Argentina, Australia, Austria, Brazil, Chile, China, Colombia, Czech Republic, Denmark, France, Germany, Greece, Guatemala, Hong Kong, Ireland, Israel, Italy, Japan, Korea South, Malasya, Mexico, Nederland, Norway, Peru, Poland, Singapore, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kindgdom, United States
Contacts
Public ContactNELVA GARCIA
MERCK SHARP & DOHME PERU S.R.L.
Outcome results
None listed