safety, tolerability, pharmacokinetics, and efficacy of acapatamab in subjects with mcrpc

Conditions: Metastatic Castration-resistant Prostate Cancer; Prostate Cancer

Summary: 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, and to determine the maximum tolerated dose (mtd) or recommended phase 2 dose (rp2d).

this is a phase i, first-in-human study to evaluate the safety and tolerability of acapatamab; a half-life extended (hle) bispecific t-cell engager (bite®) construct, alone and in combination with pembrolizumab, etanercept prophylaxis and cytochrome p450 (cyp) phenotyping cocktail in subjects with metastatic castration-resistant prostate cancer.

Eligibility criteria:
all parts inclusion criteria: * subject has provided informed consent prior to initiation of any study specific activities/procedures * 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 * subjects must have undergone bilateral orchiectomy or must be on continuous adt with a gonadotropin releasing hormone (gnrh) agonist or antagonist * total serum testosterone \</= 50 ng/dl or 1.7 nmol/l * 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 * eastern cooperative oncology group (ecog) performance status of 0 - 1 * life expectancy \>/= 6months exclusion criteria: * 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 * prior psma-targeted therapy (subjects on prior therapy may be eligible if discussed with amgen medical monitor prior to enrollment) * central nervous system (cns) metastases, leptomeningeal disease, or spinal cord compression * active autoimmune disease or any other diseases requiring immunosuppressive therapy while on study * 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 * 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: * 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 * history or evidence of interstitial lung disease or active, non-infectious pneumonitis part 3 only: - 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: * subjects taking strong oat3 inhibitors (eg, probenecid) or adjust the dosing to 1 mg po qd. * subjects with latent or active tuberculosis at screening

Keywords: acapatamab hle-bite® mcrpc metastatic castration-resistant prostate cancer prostate cancer psma bite® bispecific t-cell engager immunotherapy immuno-oncology immunooncology solid tumor psma targeted therapy