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A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Prostate Specific Membrane Antigen Half-life Extended Bispecific T-cell Engager Acapatamab in Subjects With Metastatic Castration-resistant Prostate Cancer

Safety, Tolerability, Pharmacokinetics, and Efficacy of Acapatamab in Subjects With mCRPC

Local Contact

Amgen K.K.

Midtown Tower 9-7-1 Akasaka, Minato-ku, Tokyo

clinicaltrials_japan@amgen.com

Local Local Contact

Amgen K.K.

Midtown Tower 9-7-1 Akasaka, Minato-ku, Tokyo

+81-80-7217-8592

clinicaltrials_japan@amgen.com

Complete

Feb. 05, 2019

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1. Subject has provided informed consent prior to initiation of any study specific activities/procedures
2. Subjects with histologically or cytologically confirmed mCRPC who are refractory to a novel antiandrogen therapy (abiraterone, enzalutamide, and/or apalutamide) and have failed at least 1 (but not more than 2) taxane regimens (or who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen). Progression on novel antiandrogen therapy may have occurred in the non-metastatic CRPC setting
3. Subjects must have undergone bilateral orchiectomy or must be on continuous ADT with a gonadotropin releasing hormone (GnRH) agonist or antagonist
4. Total serum testosterone </= 50 ng/dL or 1.7 nmol/L
5. Evidence of progressive disease, defined as 1 or more PCWG3 criteria:
- PSA level >/= 1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart
- nodal or visceral progression as defined by RECIST 1.1 with PCGW3 modifications
- appearance of 2 or more new lesions in bone scan
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
7. Life expectancy >/= 6months

1. Any anticancer therapy or immunotherapy within 4 weeks of start of first dose, not including luteinizing hormone-releasing hormone agonist (LHRH)/GnRH analogue (agonist/antagonist). Subjects on a stable bisophosphonate or denosumab regimen for >/= 30 days prior to randomization are eligible
2. Prior PSMA-targeted therapy (subjects on prior therapy may be eligible if discussed with Amgen medical monitor prior to enrollment)
3, Central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord compression
4. Active autoimmune disease or any other diseases requiring immunosuppressive therapy while on study
5. Needing chronic systemic corticosteroid therapy (prednisone > 10 mg per day or equivalent) or any other immunosuppressive therapies (including anti-tumor necrosis factor alpha [TNF alpha] therapies) unless stopped 7 days prior to start of first dose
6. Myocardial infarction, unstable angina, cardiac arrhythmia requiring medication, and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months of first dose of acapatamab

Part 2 only:
7. Subjects on a prior PD-1 or PD-L1 inhibitor who experienced a Grade 3 or higher immune-related adverse event prior to first day of dosing
8. History or evidence of interstitial lung disease or active, non-infectious pneumonitis

Part 3 only:
9. Evidence of active tuberculosis on chest radiograph within 3 months prior to the first dose of investigational product

Part 6 only:
Subjects are excluded from this cohort if any of the following additional criteria apply:
10. Use of any known inhibitors or inducers of drug-metabolizing enzymes within 30 days prior to study start and through start of cycle 3.
11. Use of the following components of the CYP phenotyping cocktail (midazolam HCl, warfarin sodium, vitamin K, omeprazole, and dextromethorphan HBr) within 14 days prior to cycle 1 day 1.

Male

Metastatic Castration-resistant Prostate Cancer / Prostate Cancer

Experimental: Part 1 Dose-exploration: acapatamab treatment
Part 1 dose-exploration: acapatamab is administered intravenously. The dose-exploration phase of the study will estimate the MTD of acapatamab. RP2D may be identified based on emerging safety, efficacy, and pharmacodynamic data prior to reaching an MTD.

Experimental: Part 1 Dose-expansion: acapatamab treatment
Part 1 dose-expansion: acapatamab is administered intravenously at the MTD/RP2D.

Experimental: Part 2: acapatamab + Pembrolizumab
Part 2: acapatamab is administered intravenously at the MTD/RP2D. Pembrolizumab will be administered intravenously.

Experimental: Part 3: acapatamab + Etanercept Prophylaxis
Part 3: acapatamab is administered intravenously at RP2D/MTD levels. Etanercept will be administered subcutaneously in cycle 1 only.

Experimental: Part 4: acapatamab 24 Hour Monitoring
Part 4: acapatamab is administered intravenously at RP2D/MTD with 24-hour monitoring.

Experimental: Part 5: acapatamab Outpatient Cohort
Part 5: acapatamab is administered intravenously at RP2D/MTD in an outpatient setting with 8-hour monitoring.

Experimental: Part 6: acapatamab + Cytochrome P450 (CYP) Cocktail Drug Interaction
Part 6: acapatamab is administered intravenously at RP2D/MTD. A CYP phenotyping cocktail will be administered orally.

1.Number of participants with dose-limiting toxicity [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study
2.Number of participants with treatment-emergent adverse events [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study
3.Number of participants with treatment-related adverse events [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study
4.Number of participants with clinically significant changes in vital signs [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study
5.Number of participants with clinically significant changes in electrocardiogram (ECG) [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study
6.Number of participants with clinically significant changes in clinical laboratory tests [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study

1. Maximum serum concentration (Cmax) of acapatamab [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study
2. Minimum serum concentration (Cmin) of acapatamab [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study
3. Area under the concentration-time curve (AUC) over the dosing interval of acapatamab [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5,and 6 of the study
4. Accumulation ratio of acapatamab [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study
5. Half-life of acapatamab [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study
6. Objective response (OR) [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study
7. Prostate-specific antigen (PSA) response [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study
8. Duration of response (DOR) (radiographic and PSA) [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study
9. Percentage of participants experiencing a response based on 68Gallium (68Ga)-prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/computed tomography (CT) response evaluations [Time Frame: Up to 3 years]
Parts 1, 2 and 3 only.
10. Percentage of participants experiencing a response based on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) response evaluations [Time Frame: Up to 3 years]
Parts 1, 2 and 3 only.
11. Change in time to progression (radiographic and PSA) [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study
12. Progression-free survival (PFS) (radiographic and PSA) [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study.
13. 1, 2 and 3-year overall survival (OS) [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study
14. Percentage of participants experiencing circulating tumor cells (CTC) response [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study. CTC response defined as CTC0 (reduction of CTCs > 0 to 0) or CTC conversion (>= 5 CTCs/7.5 mL blood to <= 4 CTCs/7.5 mL blood)
15. Other PCWG3-recommended endpoints - time to symptomatic skeletal events [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study
16. Other PCWG3-recommended endpoints - lactate dehydrogenase [LDH] levels [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study
17. Other PCWG3-recommended endpoints - hemoglobin levels [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study
18. Other PCWG3-recommended endpoints - neutrophil-to-lymphocyte ratio [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study
19. Other PCWG3-recommended endpoints - urine N-telopeptide levels [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study
20. Other PCWG3-recommended endpoints - alkaline phosphatase [total, bone] levels [Time Frame: Up to 3 years]
Parts 1, 2, 3, 4, 5, and 6 of the study
21. Maximum serum concentration (Cmax) of acapatamab when administered with CYP enzymes [Time Frame: Up to 3 years]
Part 6 only.
22. Area under the concentration-time curve over a 24-hour period (AUC24) of acapatamab when administered with CYP enzymes [Time Frame: Up to 3 years]
Part 6 only.
23. Half-life of acapatamab when administered with CYP enzymes [Time Frame: Up to 3 years]
Part 6 only.

July. 08, 2020

Australia/Austria/Belgium/France/Netherlands/Singapore/United States/Canada/Taiwan