| Eligibility |
Inclusion Criteria:
- Participant has provided informed consent/assent prior to initiation of any study
specific activities/procedures.
- Age = 18 years at the time of signing informed consent.
- Life expectancy of > 3 months, in the opinion of the investigator.
- Participant must have histologically or cytologically proven metastatic or locally
advanced solid tumors of known MSLN expression who have relapsed after and/or are
refractory to established and available therapies with known clinical benefit, for
which:
- No standard systemic therapy exists; or
- Standard systemic therapy has failed or is not available.
- Dose Expansion (Part 2): Participant must have one of the following malignancies:
mesothelioma, pancreatic adenocarcinoma, MSLN positive NSCLC squamous cell carcinoma
or adenocarcinoma, high grade serous ovarian carcinoma.
- At least 1 measurable or evaluable lesion as defined by modified RECIST 1.1
guidelines.
- Participants must be willing to undergo a biopsy prior to enrollment and during
treatment with AMG 994.
- Participants with treated brain metastases are eligible provided they meet the
following criteria:
- Definitive therapy was completed at least 2 weeks prior to enrollment.
- No evidence of radiographic central nervous system (CNS) progression or CNS
disease following definitive therapy and by the time of study screening. Patients
manifesting progression in lesions previously treated with stereotactic
radiosurgery may still be eligible if pseudoprogression can be demonstrated by
appropriate means and after discussion with the medical monitor.
- Any CNS disease is asymptomatic, any neurologic symptoms due to CNS disease have
returned to baseline, or non-serious CNS diseases that are asymptomatic and
deemed irreversible (eg, peripheral neuropathy), the patient is off steroids for
at least 7 days (physiologic doses of steroids are permitted), and the patient is
off or on stable doses of anti-epileptic drugs for malignant CNS disease and has
not had a seizure within 1 month prior to the screening visit.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of = 2.
- Hematologic function, as follows (transfusions or growth factor support must not be
administered within 7 days prior to obtaining screening labs):
- Absolute neutrophil count (ANC) = 1.5 x 109/L
- Platelet count = 75 x 109/L
- Hemoglobin = 9 g/dL
- Adequate renal laboratory assessments, as follows:
• Estimated glomerular filtration rate based on Modification of Diet in Renal Disease
(MDRD) calculation = 45 mL/min/1.73 m2
- Hepatic function, as follows:
- Total bilirubin (TBL) = 1.5 x upper limit of normal (ULN) or = 3 x ULN for
participants with liver metastasis
- Aspartate transaminase (AST) = 3 x ULN or = 5 x ULN for participants with liver
metastasis
- Alanine aminotransferase (ALT) = 3 x ULN or = 5 x ULN for participants with liver
metastasis
- Alkaline phosphatase = 2.5 x ULN or = 5 x ULN for participants with liver
metastasis
Exclusion Criteria:
Disease Related
- Primary brain tumor, untreated or symptomatic brain metastases and leptomeningeal
disease.
Other Medical Conditions
- History of other malignancy within the past 2 years, with the following exception[s]:
- Malignancy treated with curative intent and with no known active disease present
for = 3 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 cervical carcinoma in situ without evidence of disease.
- Adequately treated breast ductal carcinoma in situ without evidence of disease.
- Prostatic intraepithelial neoplasia without evidence of prostate cancer.
- Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in
situ.
- Participants with NSCLC squamous cell carcinoma (Part 1), MSLN negative NSCLC squamous
cell carcinoma (Part 2), or MSLN negative NSCLC adenocarcinoma (Part 2) once the
participant has been screened for MSLN expression.
- Participants with sarcomatoid mesothelioma and small cell lung cancer will be excluded
from both the Dose Exploration (Part 1) and Dose Expansion (Part 2) parts of the
study.
- History of solid organ transplantation.
- Major surgery within 28 days of study day 1.
Prior/Concomitant Therapy
- Anti-tumor therapy (radiotherapy, chemotherapy, antibody therapy, molecular targeted
therapy, or investigational agent) within 21 days prior to study day 1.
- Treatment with a checkpoint inhibitor within 9 weeks prior to study day 1.
- Live vaccine therapy within 4 weeks prior to study drug administration.
- Current treatment or within 14 days of day 1 with immunosuppressive corticosteroid
defined as > 10 mg prednisone daily or equivalent. Steroids with no minimal systemic
effect (such as topical or inhalation) are permitted.
Prior/Concurrent Clinical Study Experience
- Currently receiving treatment in another investigational device or drug study, or less
than 21 days prior to study day 1 since ending treatment on another investigational
device or drug study(ies).
- Evidence of active or radiological sequelae of non-infectious pneumonitis.
- History of any immune-related colitis. Infectious colitis is allowed if evidence of
adequate treatment and clinical recovery exists and at least 3 months interval
observed since diagnosis of colitis.
- History of allergic reactions or acute hypersensitivity reaction to antibody
therapies.
- Positive/non-negative test results for human immunodeficiency virus (HIV).
- Hepatitis B and C based on the following results:
- Positive for hepatitis B surface antigen (HBsAg) (indicative of chronic hepatitis
B or recent acute hepatitis B)
- Negative HBsAG and positive for hepatitis B core antibody: hepatitis B virus DNA
by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA
suggests occult hepatitis B.
- Positive hepatitis C virus antibody (HCVAb): hepatitis C virus RNA by PCR is
necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C.
- Active infection requiring oral or intravenous therapy.
- Active or history of any autoimmune disease or immunodeficiencies. Participants with
diabetes Type 1, vitiligo, psoriasis, hypo- or hyper-thyroid disease not requiring
immunosuppressive treatment are permitted.
- Myocardial infarction within 6 months of study day 1, symptomatic congestive heart
failure (New York Heart Association > class II), unstable angina, or cardiac
arrhythmia requiring medication.
- Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to
Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1, or are
stable and well controlled with minimal, local, or noninvasive intervention AND there
is agreement to allow by both the investigator and the Amgen Medical Monitor.
- Any history of grade 3 or higher colitis, pneumonitis, or neurological toxicity
OR
- Unresolved toxicities from prior checkpoint inhibitor therapy, defined as not
having resolved to CTCAE v5.0 grade 1.
- Exception: - clinically stable hypothyroid status managed with hormone
replacement therapy, is permitted
Other Exclusions
- Female participant is pregnant or breastfeeding or planning to become pregnant or
breastfeed during treatment and for an additional 6 months after the last dose of AMG
994 and/or AMG 404.
- Female participants of childbearing potential unwilling to use 1 highly effective
method of contraception during treatment and for an additional 6 months after the last
dose of AMG 994 and/or AMG 404.
- Female participants of childbearing potential with a positive pregnancy test assessed
at day 1 by a serum pregnancy test.
- Male participants 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 8 months after the last dose of
AMG 994 and/or AMG 404.
- Male participants unwilling to abstain from donating sperm during treatment and for an
additional 8 months after the last dose of AMG 994 and/or AMG 404.
- Participant has known sensitivity to any of the products or components to be
administered during dosing.
- Participant likely to not be available to complete all protocol-required study visits
or procedures, and/or to comply with all required study procedures to the best of the
participant and investigator's knowledge.
- History or evidence of any other clinically significant disorder, condition or disease
(with the exception of those outlined above) that, in the opinion of the investigator
or Amgen physician, if consulted, would pose a risk to participant safety or interfere
with the study evaluation, procedures or completion.
|
