A Study of Tarlatamab (AMG 757) in Participants With Neuroendocrine Prostate Cancer
- Interventional
- Recruiting
- NCT04702737
Contact Information
A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of Delta-like Protein 3 Half-life Extended Bispecific T-cell Engager AMG 757 in Subjects With De Novo or Treatment Emergent Neuroendocrine Prostate Cancer
To evaluate the safety and tolerability of Tarlatamab and will determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).
Gender
Male
Age Group
18 Years and up
Accepting Healthy Volunteers?
No
Inclusion Criteria:
- Participant has provided informed consent prior to initiation of any study specific activities/procedures.
- Men aged ≥ 18 years at time of signing the informed consent.
- Metastatic de novo or treatment-emergent neuroendocrine prostate cancer (NEPC) defined by histological, immunohistochemistry, or genomic analyses of baseline tumor tissue (by local assessment) or circulating tumor DNA (ctDNA) (by local assessment) as per protocol
- At least 1 line of prior systemic treatment per protocol.
- For participants with treatment-emergent NEPC or de novo NEPC with histologic evidence of prostate cancer with neuroendocrine differentiation.
- Participants with treatment-emergent NEPC or de novo NEPC with histologic evidence of prostate cancer with neuroendocrine differentiation without a history of bilateral orchiectomy are required to remain on luteinizing hormone-releasing hormone (LHRH) analogue therapy during the course of protocol therapy
- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 per Prostate Cancer Working Group 3 (PCWG3) modifications
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
- Participants with treated brain metastases are eligible provided they meet defined criteria
- Adequate organ function as defined in protocol
Exclusion Criteria:
- History of other malignancy within the past 2 years, with exceptions:
- Malignancy treated with curative intent and with no known active disease present for ≥ 2 years before enrollment and felt to be at low risk for recurrence by the treating physician
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
- Adequately treated non-muscle invasive urothelial carcinoma
- History or presence of hematological malignancies unless curatively treated with no evidence of disease ≥ 2 years
- Untreated or symptomatic brain metastases and leptomeningeal disease
- Anti-tumor therapy within 28 days of study day 1; concurrent use of hormone deprivation therapy for hormone refractory prostate is permitted; participants on a stable bisphosphonate or denosumab for ≥ 30 days prior to study day 1 are eligible
Exceptions:
- Participants who received conventional chemotherapy are eligible if at least 14 days have elapsed and if all treatment-related toxicities have resolved to Grade ≤ 1
- Prior palliative radiotherapy must have been completed at least 7 days before the first dose of Tarlatamab
- Participants who received androgen signaling inhibitor are eligible if at least 14 days have elapsed and if all treatment-related toxicity has been resolved to Grade ≤ 1
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior study day 1
- Active autoimmune disease requiring systemic treatment within the past 2 years
- Known positive test for human immunodeficiency virus (HIV) or hepatitis
- Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade 0 or 1 (with the exception of alopecia or toxicities that are stable and well-controlled)
- History of hypophysitis or pituitary dysfunction
- Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
- Participants on prior DLL3-targeted therapy may be eligible if discussed with Amgen medical monitor prior to enrollment
- History or evidence of SARS-COV2 infection unless agreed upon with Medical Monitor and with no acute symptoms of COVID19 disease within 14 days prior to first dose of IP (counted from day of positive test for asymptomatic subjects).
- Participant has provided informed consent prior to initiation of any study specific activities/procedures.
- Men aged ≥ 18 years at time of signing the informed consent.
- Metastatic de novo or treatment-emergent neuroendocrine prostate cancer (NEPC) defined by histological, immunohistochemistry, or genomic analyses of baseline tumor tissue (by local assessment) or circulating tumor DNA (ctDNA) (by local assessment) as per protocol
- At least 1 line of prior systemic treatment per protocol.
- For participants with treatment-emergent NEPC or de novo NEPC with histologic evidence of prostate cancer with neuroendocrine differentiation.
- Participants with treatment-emergent NEPC or de novo NEPC with histologic evidence of prostate cancer with neuroendocrine differentiation without a history of bilateral orchiectomy are required to remain on luteinizing hormone-releasing hormone (LHRH) analogue therapy during the course of protocol therapy
- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 per Prostate Cancer Working Group 3 (PCWG3) modifications
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
- Participants with treated brain metastases are eligible provided they meet defined criteria
- Adequate organ function as defined in protocol
Exclusion Criteria:
- History of other malignancy within the past 2 years, with exceptions:
- Malignancy treated with curative intent and with no known active disease present for ≥ 2 years before enrollment and felt to be at low risk for recurrence by the treating physician
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
- Adequately treated non-muscle invasive urothelial carcinoma
- History or presence of hematological malignancies unless curatively treated with no evidence of disease ≥ 2 years
- Untreated or symptomatic brain metastases and leptomeningeal disease
- Anti-tumor therapy within 28 days of study day 1; concurrent use of hormone deprivation therapy for hormone refractory prostate is permitted; participants on a stable bisphosphonate or denosumab for ≥ 30 days prior to study day 1 are eligible
Exceptions:
- Participants who received conventional chemotherapy are eligible if at least 14 days have elapsed and if all treatment-related toxicities have resolved to Grade ≤ 1
- Prior palliative radiotherapy must have been completed at least 7 days before the first dose of Tarlatamab
- Participants who received androgen signaling inhibitor are eligible if at least 14 days have elapsed and if all treatment-related toxicity has been resolved to Grade ≤ 1
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior study day 1
- Active autoimmune disease requiring systemic treatment within the past 2 years
- Known positive test for human immunodeficiency virus (HIV) or hepatitis
- Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade 0 or 1 (with the exception of alopecia or toxicities that are stable and well-controlled)
- History of hypophysitis or pituitary dysfunction
- Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
- Participants on prior DLL3-targeted therapy may be eligible if discussed with Amgen medical monitor prior to enrollment
- History or evidence of SARS-COV2 infection unless agreed upon with Medical Monitor and with no acute symptoms of COVID19 disease within 14 days prior to first dose of IP (counted from day of positive test for asymptomatic subjects).