Inclusion Criteria:
- - Subject has provided informed consent prior to initiation of any study specific
activities/procedures.
- - Age ≥19 years at the time of signing the informed consent.
- - Histologically confirmed relapsed/refractory extra-pulmonary neuroendocrine
carcinoma.
Neuroendocrine carcinoma includes small cell carcinoma, large cell
carcinoma, and mixed histology of neuroendocrine and other histology (e.g.,
adenoneuroendocrine carcinoma, urothelial carcinoma with neuroendocrine component).
In patients with prostate cancer, treatment-emergent neuroendocrine carcinoma
(initially adenocarcinoma, but transdifferentiate into neuroendocrine carcinoma
after androgen deprivation therapy) will be permitted.
- - Cohort 1 (gastrointestinal and pancreaticobiliary cohort): cancers originated from
stomach, small intestine, colorectal, pancreas, or bile ducts.
- - Cohort 2 (genitourinary cohort): cancers originated from prostate, bladder, ureter,
urethra, or kidney.
- - Subject has progressed or recurred following 1 platinum-based regimen:
- documented first disease progression must be during or following first-line
platinum-based systemic chemotherapy.
For patients with prostate cancer, especially
in cases with treatment-emergent neuroendocrine carcinoma, platinum-based
chemotherapy will not need to be the first line therapy.
- - patients who received treatment for localized disease who recur are eligible.
- - patients who received adjuvant Platinum-Etoposide (EP) after resection of their
primary tumor who recur are eligible.
- - Measurable disease as defined per RECIST 1.1 within the 21-day screening period.
• Screening scans performed as SOC(Standard of Care) and prior to informed consent,
may be used to confirm subject eligibility if completed within the 21-day screening
period, provided that informed consent for the use of these scans is obtained prior
to any transfer of data.
- - In patients with prostate cancer, patients without RECIST-defined measurable
lesion can be included, if disease can be evaluated with Prostate Cancer
Working Group(PCWG)-3 criteria.
- - Eastern Cooperative Oncology Group (ECOG) PS(Performance Status) of 0 - 2.
- - Minimum life expectancy of 12 weeks.
- - Adequate organ function, defined as follows:
• Hematological function: Absolute neutrophil count ≥ 1.5 x 10^9 /L Platelet count ≥
100 x 10^9/L Hemoglobin > 9 g/dL (90 g/L)
• Coagulation function: Prothrombin Time (PT)/International Normalized Ratio (INR)
and Partial Thromboplastin Time (PTT) or activated Partial Thromboplastin Time
(APTT) ≤ 1.5 x institutional upper limit of normal (ULN) except for subjects
undergoing new class anticoagulant therapy (eg, Edoxaban), stable dose for 2 weeks
required prior to enrollment.
• Renal function: estimated glomerular filtration rate (eGFR) based on Modification
of Diet in Renal Disease (MDRD) calculation ≥ 30 mL/min/1.73 m^2 or creatinine
clearance ≥ 30 mL/min as determined by Cockcroft-Gault equation (Cockcroft and Gault
1976)
• Hepatic function: aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) < 3 x ULN (or <5 x ULN for subjects with liver involvement) total bilirubin
(TBL) <1.5 x ULN (<2 x ULN for subjects with liver involvement) (except participants
with Gilbert syndrome who must have total bilirubin <3.0 mg/dL)
• Pulmonary function: no clinically significant pleural effusion. Pleural effusion
managed with indwelling pleural catheter (eg, PleurX) are allowed baseline oxygen
saturation >90% on room air. • Cardiac function: cardiac ejection fraction ≥50%, no clinically significant
pericardial effusion as determined by an echocardiogram (ECHO) or multigated
acquisition (MUGA) scan, and no clinically significant electrocardiogram (ECG)
findings Provision of evaluable tumor samples for central testing (archival or
in-study biopsy)
Exclusion Criteria:
- - Symptomatic central nervous system (CNS) metastases:
• Subjects with treated brain metastases are eligible provided the following
criteria are met:
- Subject is asymptomatic from brain metastases.
- - Whole brain radiation or surgery was completed at least 2 weeks prior to first dose
of study treatment (stereotactic radiosurgery completed at least 7 days prior to
first dose of study treatment)
- Any CNS disease is clinically stable, subject is off steroids for CNS disease for at
least 5 days (unless steroids are indicated for a reason unrelated to CNS disease),
and subject is off or on stable doses of anti-epileptic drugs at least 14 days prior
to first dose of study treatment • Subjects with untreated brain metastases that are
asymptomatic and do not require corticosteroids, nor local therapy per investigators
standard of practice are allowed Diagnosis or evidence of leptomeningeal disease.
Prior history of immune checkpoint inhibitors resulting in:
- - Any severe or life-threatening immune-mediated adverse event, History of
immune-mediated encephalitis or other immune-mediated CNS event (any grade)
- Grade ≥ 2 immune-mediated recurrent pneumonitis, Infusion-related reactions leading
to permanent discontinuation of immunotherapy agent Exception: Subjects with a
history of immune checkpoint inhibitor-induced endocrinopathy which is clinically
stable on replacement therapy.
- - Active autoimmune disease that has required systemic treatment (except
replacement therapy) within the past 2 years or any other diseases requiring
immunosuppressive therapy while on study.
- - History of solid organ transplantation.
- - History of other malignancy within the past 2 years, with the following
exceptions:
- low-risk malignancy treated with curative intent and with no known active disease
present for ≥ 1 year before enrollment and believed to be at low risk for recurrence
per investigator discretion.
- - adequately treated non-melanoma skin cancer or lentigo maligna without evidence of
disease, cervical carcinoma in situ without evidence of disease, breast ductal
carcinoma in situ without evidence of disease.
- - prostatic intraepithelial neoplasia without evidence of prostate cancer.
(For
non-prostate cancer patient)
- - adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ.
- - Myocardial infarction and/or symptomatic congestive heart failure (New York
Heart Association > class II) within 12 months prior to first dose of study
treatment (Section 11.9).
- - History of arterial thrombosis (eg, stroke or transient ischemic attack) within
12 months prior to first dose of study treatment.
- - Presence/history of viral infection: Human immunodeficiency virus (HIV)
infection.
- - Subjects with HIV infection on antiviral therapy and undetectable viral load are
permitted with a requirement for regular monitoring for reactivation for the
duration of treatment on study per local or institutional guidelines, Active
hepatitis C infection (subjects with detectable hepatitis C antibody [HCV Ab] and
HCV RNA viral load above the limit of quantification),
- Subjects with presence of HCV Ab and HCV RNA viral load below the limit of
quantification (HCV RNA negative) with or without prior treatment are allowed Active
hepatitis B infection (presence of hepatitis B surface antigen [HBsAg] and hepatitis
B virus [HBV] DNA viral load above the limit of quantification [HBV DNA positive])
- Subjects with resolved HBV infection defined as absence of HBsAg and presence of HBV
core antibody (anti-HBc) followed by an HBV DNA viral load below the limit of
quantification (HBV DNA negative) are allowed, with a requirement for regular
monitoring for reactivation for the duration of treatment on the study and assessing
the need for HBV prophylaxis therapy per local or institutional guidelines.
- - Subjects with chronic HBV infection inactive carrier state defined as presence of
HBsAg and HBV DNA viral load below the limit of quantification [HBV DNA negative]
are allowed, with a requirement for regular monitoring for reactivation for the
duration of treatment on the study and assessing the need for HBV prophylaxis
therapy per local or institutional guidelines.
Receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy
within 7 days prior to first dose of study treatment:
- - Prophylactic dexamethasone required by the protocol and any anti-emetic therapies
are allowed.
- - Low-dose corticosteroids (prednisone ≤10 mg per day or equivalent is permitted
during the trial)
- Subject with symptoms and/or clinical signs and/or radiographic signs that
indicate an acute and/or uncontrolled active systemic infection within 7 days
prior to the first dose of study treatment.
- - Evidence of interstitial lung disease or active, non-infectious pneumonitis.
- - Prior therapy with tarlatamab.
- - Prior therapy with any selective inhibitor of the DLL3 pathway.
- - Subject received more than 2 prior systemic therapy regimens for EPNECs.
In
patients with treatment-emergent prostate neuroendocrine carcinoma, treatments
given before histological confirmation of neuroendocrine cancer (e.g., androgen
deprivation therapy, androgen receptor targeted agents such as enzalutamide and
abiraterone, and docetaxel) are not considered as previous treatment for
metastatic/recurrent EPNEC.
- - Prior anti-cancer therapy within 21 days prior to first dose of study
treatment.
Exceptions:
- - Subjects who received conventional chemotherapy are eligible if at least 14 days
have elapsed and if all treatment-related toxicity has been resolved to grade ≤ 1,
or to levels dictated in the eligibility criteria, before first dose of study
treatment, with the exception of alopecia or toxicities considered irreversible
(defined as having been present and stable for >30 days) which are not otherwise
described in the exclusion criteria.
- - Prior palliative radiotherapy must have been completed at least 7 days before the
first dose of study treatment.
- - Receiving anti-cancer therapy such as chemotherapy, immunotherapy, or targeted
therapy.
Patients who are receiving adjuvant hormonal therapy for resected
breast cancer may be eligible (refer also to exclusion related to history of
other malignancies). Additionally, in patients with treatment-emergent prostate
neuroendocrine carcinoma, continuation of androgen deprivation therapy is
permitted.
- - Any herbal or prescription/non-prescription medications known to inhibit
membrane transporters P-glycoprotein (P-gp) and/or breast cancer resistance
protein (BCRP) within 7 days prior to the first dose of study treatment.
Any herbal or prescription/non-prescription medications known to be moderate or strong
inhibitors of cytochrome P450 3A (CYP3A) enzymes (including but not limited to
clarithromycin, itraconazole, ketoconazole) within 7 days prior to the first dose of
study treatment.
- - Any herbal or prescription/non-prescription medications known to be moderate or
strong inducers of CYP3A enzymes within 28 days prior to first dose of study
treatment.
- - Subjects who have reached the limit dose of prior treatment with cardiotoxic drugs
such as other anthracyclines.
- - Major surgical procedures within 28 days prior to first dose of study treatment.
Treatment with live virus, including live-attenuated vaccination, within 14 days prior to
the first dose of study treatment. Inactive vaccines (eg, non-live or non-replicating
agent) and live viral non-replicating vaccines (eg, Jynneos for Monkeypox infection)
within 3 days prior to first dose of study treatment.
- - Currently receiving treatment in another investigational device or drug study, or
less than 30 days since ending treatment on another investigational device or drug
study(ies).
Other investigational procedures while participating in this study are
excluded.
- - Female subjects of childbearing potential unwilling to use protocol specified method
of contraception see Appendix 5 (Section 11.5) during treatment and for an
additional 60 days after the last dose of tarlatamab.
- - Female subjects who are breastfeeding or who plan to breastfeed while on study
through 60 days after the last dose of tarlatamab.
- - Female subjects planning to become pregnant or donate eggs while on study through 60
days after the last dose of tarlatamab.
- - Female subjects of childbearing potential with a positive pregnancy test assessed at
screening by a serum or urine pregnancy test.
- - Male subjects with a female partner of childbearing potential who are unwilling to
practice sexual abstinence (refrain from heterosexual intercourse) or use
contraception during treatment and for an additional 60 days after the last dose of
tarlatamab.
- - Male subjects with a pregnant partner who are unwilling to practice abstinence or
use a condom during treatment and for an additional 60 days after the last dose of
tarlatamab.
- - Male subjects unwilling to abstain from donating sperm during treatment and for an
additional 60 days after the last dose of tarlatamab Subject has known sensitivity
or is contraindicated to any of the products or components to be administered during
dosing.
- - Subject likely to not be available to complete all protocol-required study visits or
procedures, and/or to comply with all required study procedures.
- History or evidence of any other clinically significant disorder, condition or
disease
