Matthias Preusser, MD Principal Investigator Medical Oncologist. Head of Clinical Division of Oncology, Medical University of Vienna Rupert Bartsch, MD, PhD Principal Investigator Consultant Hematology and Medical Oncology, Medical University of Vienna
1. Efficacy: Local determination of intracranial objective response rate (ORR-IC) in cohort 1 and cohort 2. (Time Frame - From baseline to the date of first documented progression, death from any cause, or treatment discontinuation from any reason, whichever came first, assessed up to 12 months): Rate of patients with complete response (CR) or partial response (PR) determined locally by investigator, using Response Assessment in Neuro-Oncology Brain Metastases (RANO)-BM criteria in cohort 1 and cohort 2.
2. Efficacy: Overall survival (OS) rate at 3 months in cohort 3. (Time Frame - From baseline up to 3 months): 3-month OS, defined as the rate of patients alive at 3 months after treatment initiation in cohort 3.
Secondary outcome:
1. Efficacy: Central determination of ORR in cohort 1, cohort 2, and cohort 3. (Time Frame - From baseline to the date of first documented progression, death from any cause, or treatment discontinuation from any reason, whichever came first, assessed up to 12 months): ORR, defined as the rate of patients with CR or PR determined by central review as per RANO-BM in cohort 1 and cohort 2 and per ESMO-EANO in cohort 3 for intracranial lesions, and per RECIST v.1.1 for extracranial and overall lesions (bicompartmental ORR) in all cohorts.
2. Efficacy: progression-free survival (PFS) in cohort 1, cohort 2, and cohort 3. (Time Frame - From baseline up to 12 months): PFS, defined as the period from treatment initiation to the first occurrence of disease progression or death from any cause or treatment discontinuation from any other reason, whichever occurs first, that will be centrally reviewed as per RANO-BM for intracranial lesions in cohort 3 and RECIST v.1.1 for extracranial and overall lesions in all cohorts.
3. Efficacy: bicompartmental clinical benefit rate (CBR) in cohort 1, cohort 2, and cohort 3. (Time Frame - From baseline to the date of first documented progression, death from any cause, or treatment discontinuation from any reason, whichever came first, assessed up to 12 months): CBR, defined as the rate of patients with objective response (CR or PR), or stable disease for at least 24 weeks, centrally reviewed as per RANO-BM in cohort 1 and cohort 2 and ESMO-EANO in cohort 3 for intracranial lesions, and RECIST v.1.1 for extracranial and overall lesions (bicompartmental CBR) in all cohorts.
4. Efficacy: disease control rate (DCR) in cohort 1, cohort 2, and cohort 3. (Time Frame - From baseline to the date of first documented progression, death from any cause, or treatment discontinuation from any reason, whichever came first, assessed up to 12 months): DCR, defined as the rate of patients with objective response (CR or PR), or stable disease (SD), determined by central review as per RANO-BM in cohort 1 and cohort 2 and ESMO-EANO in cohort 3 for intracranial lesions, and RECIST v.1.1 for extracranial and overall lesions (bicompartmental DCR) in all cohorts.
5. Efficacy: time to response (TTR) in cohort 1, cohort 2, and cohort 3. (Time Frame - From baseline to the date of first documented progression, death from any cause, or treatment discontinuation from any reason, whichever came first, assessed up to 12 months): TTR, defined as the period from the treatment initiation to time of the first objective tumor response (tumor shrinkage of ≥ 30%) observed for patients who achieved a CR or PR, centrally reviewed as per RANO-BM in cohort 1 and cohort 2 and ESMO-EANO in cohort 3 for intracranial lesions, and RECIST v.1.1 for extracranial and overall lesions in all cohorts.
6. Efficacy: duration of response (DoR) in cohort 1, cohort 2, and cohort 3. (Time Frame - From baseline to the date of first documented progression, death from any cause, or treatment discontinuation from any reason, whichever came first, assessed up to 12 months): DOR, defined as the period from the first occurrence of a documented objective response to disease progression or death from any cause, observed for patients who achieved a CR or PR. It will be centrally reviewed as per RANO-BM in cohort 1 and cohort 2 and ESMO-EANO in cohort 3 for intracranial lesions, and RECIST v.1.1 for extracranial and overall lesions in all cohorts.
7. Efficacy: best percentage of change in tumor burden in cohort 1, cohort 2, and cohort 3. (Time Frame - From baseline to the date of first documented progression, death from any cause, or treatment discontinuation from any reason, whichever came first, assessed up to 12 months): Best percentage of change in tumor burden centrally reviewed as per RANO-BM in cohort 1 and cohort 2 and ESMO-EANO in cohort 3 for intracranial lesions, and RECIST v.1.1 for extracranial and overall measurable lesions in all cohorts.
8. Efficacy: overall survival (OS) in cohort 1 and cohort 2. (Time Frame - From baseline to the date of first documented progression, death from any cause, or treatment discontinuation from any reason, whichever came first, assessed up to 12 months): OS, defined as the period from treatment initiation to death from any cause or last available follow-up in cohort 1 and cohort 2.
9. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) in cohort 1, cohort 2, and cohort 3. (Time Frame - From baseline to the date of first documented progression, death from any cause, or treatment discontinuation from any reason, whichever came first, assessed up to 12 months): Safety and tolerability of HER3-DXd as per National Cancer Institute Common Terminology Criteria for Adverse Events (AEs) Version 5.0 (NCI-CTCAE v.5.0) in all cohorts.
10. Patient reported outcomes (PROs) with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-30) of patients in cohort 1, cohort 2, and cohort 3. (Time Frame - From baseline to the date of first documented progression, death from any cause, or treatment discontinuation from any reason, whichever came first, assessed up to 12 months): Assessment of overall change from baseline in QoL with the EORTC QLQ-C30 scale to measure cancer patients' physical, psychological and social functions in all cohorts. All scales and single items are transformed into scores ranging from 0 to 100. A high score for a functional scale represents a high level of functioning, whereas a high score for a symptom scale/single item represents a high level of symptomatology.
11. Effects of the tumor and its function with the European Organization for Research and Treatment of Cancer brain cancer-specific Quality of Life Questionnaire (EORTC QLQ-BN20) of patients in cohort 1, cohort 2, and cohort 3. (Time Frame - From baseline to the date of first documented progression, death from any cause, or treatment discontinuation from any reason, whichever came first, assessed up to 12 months): Assessment of overall change from baseline of the effects of brain tumors and its treatment on symptoms, functions and health-related quality of life with the brain specific tool (EORTC QLQ-BN20) in all cohorts. All scales and single items are transformed into scores ranging from 0 to 100. A high score for a functional scale represents a high level of functioning, whereas a high score for a symptom scale/single item represents a high level of symptomatology.
12. Effects of the tumor and its function using the European Organization for Research and Treatment of Cancer breast cancer-specific Quality of Life Questionnaire (EORTC QoL-BR45) of breast cancer patients in cohort 1. (Time Frame - From baseline to the date of first documented progression, death from any cause, or treatment discontinuation from any reason, whichever came first, assessed up to 12 months): Assessment of overall change from baseline of the effects in QoL of breast cancer patients in cohort 1 with the breast specific tool EORTC QLQ-BR45 scale to measure physical, psychological and social functions. All scales and single items are transformed into scores ranging from 0 to 100. A high score for a functional scale represents a high level of functioning, whereas a high score for a symptom scale/single item represents a high level of symptomatology.
13. Assessment of overall change from baseline of the effects of the tumor in and its treatment in neurologic function using the Neurologic Assessment in Neuro-Oncology (NANO) scale in cohort 1, cohort 2, and cohort 3. (Time Frame - From baseline to the date of first documented progression, death from any cause, or treatment discontinuation from any reason, whichever came first, assessed up to 12 months): Differences in neurologic assessment in NANO scale in all cohorts. High-scale values represent impaired neurological performances. NANO scale differences (values before and after treatment) below or equal to 0 represent a stable or improved neurological performance and vice versa.
Patritumab deruxtecan (HER3-DXd): HER3 directed antibody drug conjugate (ADC) that is comprised of a fully human anti-HER3 immunoglobulin gamma-1 (IgG1) monoclonal antibody attached to a topoisomerase I inhibitor payload (an exatecan derivative, DXd) via a stable tetrapeptide-based cleavable linker.
Quelle: ClinicalTrials.gov
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