| Eligibility |
Inclusion Criteria:
1. Have a signed informed consent form prior to any study specific procedures or
treatment
2. Be =18 years of age (male or female) at the time of consent
3. Have 1 of the following histologically or cytologically confirmed tumor types with
qualifying characteristics, and have received a minimum of 2 (and no more than 5)
lines of prior therapy for metastatic (Stage IV) disease:
1. RCC (renal cell carcinoma - clear cell or papillary)
2. SCLC (small cell lung cancer) OR have received a minimum of 3 (and no more than
5) lines of prior therapy for metastatic (Stage IV) disease:
3. GC (gastric adenocarcinoma)
4. Human epidermal growth factor receptor positive (HER2+) MBC (metastatic breast
cancer)
5. Other solid tumors (e.g., non-small cell lung cancer, colorectal cancer,
carcinoma of unknown primary) with the exception of rapidly progressing neoplasms
(e.g., pancreatic cancer, glioblastoma, hepatocellular carcinoma)
Note: Subjects with RCC and GC are a priority and should constitute approximately 50%
(12 subjects) of the enrolled popululation. Enrollment of all others will be capped
when reaching a combined 50%, in order to maintain 12 slots for subjects with RCC and
GC.
4. Have at least 1 radiologically measurable lesion as per RECIST v 1.1, defined as a
lesion that is at least 10 mm in longest diameter or lymph node and that is at least
15 mm in short axis imaged by CT scan or magnetic resonance imaging (MRI) and obtained
by imaging within 28 days prior to screening. Tumor lesions situated in a previously
irradiated area are considered measurable if progression has been demonstrated in such
lesions
5. Have resolution of all previous treatment related toxicities to Grade 1 severity or
lower, except for stable sensory neuropathy (= Grade 2) and alopecia. If the subject
received major surgery or radiation therapy of >30 Gy, they must have recovered from
the toxicity and/or complications from the intervention
6. Provided there are suitable and accessible lesions, no biopsy contraindications,
minimal risk of complications and a positive informed decision, subject as are willing
to provide fresh tissue for biomarker analysis, and, based on the adequacy of the
tissue sample quality, for assessment of biomarker status. Two biopsies will be
necessary: at baseline (within 30 days prior to first dose) and within 7 days after
Cycle 3/Day 1.
Newly obtained biopsy specimens are preferred to archived samples and formalin- fixed,
paraffin-embedded block specimens are preferred to slides. In the event a fresh
pre-treatment biopsy is not able to be provided, the most recent archival biopsy must
be provided in its place
7. Have Eastern Cooperative Oncology Group performance status of 0 or 1 and sustained
between screening and initiation of dosing on Day 1
8. QT interval corrected for heart rate using Fridericia's (QTcF) method =450 msec
9. Have an albumin level of =3 g/dL at screening
10. Have life expectancy of 3 months or greater as determined by the treating physician
11. Have adequate organ function within 15 days prior to first administration of study
drug on Day 1, as defined by meeting all of the following criteria:
1. Total bilirubin =1.5 × upper limit of normal (ULN) OR direct bilirubin = ULN for
subjects with total bilirubin levels >1.5 x ULN
2. Aspartate aminotransferase and alanine aminotransferase =2.5 × ULN or =5 × ULN
for subjects with known hepatic metastases
3. Fasting serum glucose within normal range and hemoglobin A1c =8%
4. Thyroid function tests (thyroid stimulating hormone [TSH] within normal limits
for subjects with normal thyroid function and free thyroxine [FT4]) within normal
limits for subjects on thyroid treatment
12. Have adequate renal function within 15 days prior to first administration of study
drug on Day 1, as defined by creatinine =1.5 × ULN and creatinine clearance =30
mL/min, as per the below Cockcroft Gault formula
13. Have adequate hematologic function within 15 days prior to first administration of
study drug on Day 1, as defined by meeting all of the following criteria:
1. Hemoglobin =9 g/dL (uncorrected by red blood cell transfusion or erythropoietin
support)
2. Absolute neutrophil count =1.5 × 109/L
3. Platelet count =100 × 109/L
14. Have adequate coagulation function within 15 days prior to first administration of
study drug on Day 1, as defined by either of the following criteria:
1. International normalized ratio (INR) <1.5 × ULN OR for subjects receiving
warfarin or low molecular weight heparin, the subject must, in the investigator's
opinion, be clinically stable with no evidence of active bleeding while receiving
anticoagulant therapy. The INR for these subjects may exceed 1.5 × ULN if that is
the goal of anticoagulant therapy
2. Activated partial thromboplastin time (aPTT) <1.5 × ULN unless subject is
receiving anticoagulant therapy, provided prothrombin time or aPTT is within
therapeutic range of intended use of anticoagulants
15. Female subject of childbearing potential must have a negative urine or serum pregnancy
within 72 hours prior to receiving the first dose of study medication. If the urine
test is positive or cannot be confirmed as negative, a serum pregnancy test will be
required
16. Female subject of childbearing potential must be willing to use an adequate form of
contraception from the first dose of study medication through 90 days after the last
dose of study drug
17. Female subject must agree not to breastfeed and not to donate ova starting at
screening and throughout the study treatment, and for 90 days after the last dose of
study drug
18. Male subject with a pregnant or breastfeeding partner(s) must agree to remain
abstinent or use a condom for the duration of the pregnancy or for the time partner is
breastfeeding throughout the study period and for 90 days after the last dose of study
drug
19. Male subject with female partner(s) of childbearing potential must not donate sperm
during the treatment period and for at least 90 days after the last dose of study drug
20. Male subject with female partner(s) of childbearing potential should agree to use a
highly effective method of contraception during the treatment period and for at least
90 days after the last dose of the study drug
21. Be willing and have the ability to comply with scheduled visits (including
geographical proximity), treatment plans, laboratory tests, and other study
procedures.
Exclusion Criteria:
1. Had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2
weeks prior to the first dose of study treatment or who has not recovered from adverse
reactions due to a previously administered agent or major surgery
2. Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of the first dose of treatment
3. Has a diagnosis of immunodeficiency or receiving systemic steroid therapy or any other
form of immunosuppressive therapy within 7 days prior to the first dose of study
treatment. The use of physiologic doses of corticosteroids (=30 mg/day of
hydrocortisone, =10 mg/day of prednisone, =2 mg/day of dexamethasone, or equivalent)
may be approved after consultation with the sponsor
4. Has taken a medication that is a strong CYP3A4 inhibitor or inducer within 4 weeks of
the first dose of treatment (see Appendix 12)
5. Has known history of active tuberculosis
6. Has known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
7. Has known active Hepatitis B (anti hepatitis B surface antibody, anti hepatitis B core
antibody, hepatitis B surface antigen [HBsAg]) or Hepatitis C (hepatitis C antibody)
infection
8. Has a current diagnosis of severe acute respiratory syndrome coronavirus (SARS CoV) 2
infection confirmed by reverse transcription polymerase chain reaction (PCR) test.
Subject needs to have a negative PCR test at screening and a negative PCR test within
14 days prior to the first dose of study treatment
9. Has a history of clinically severe autoimmune disease, or a history of organ
transplant
10. Has insulin dependent (Type I) diabetes or poorly controlled Type II diabetes (per
clinical discretion) with hemoglobin A1c >8%
11. Has known additional malignancy that is progressing or required active treatment
within previous 5 years. Exceptions include basal cell carcinoma or squamous cell
carcinoma of the skin that has undergone potentially curative therapy, superficial
bladder cancer, or in situ cervical cancer. Subjects with other malignancies are
eligible if they were cured by surgery alone or surgery plus radiotherapy and have
been continuously disease free for at least 5 years
12. Has known active central nervous system metastases and/or carcinomatous meningitis.
Subjects with previously treated brain metastases may participate provided they are
stable (without evidence of disease progression by imaging for at least 4 weeks prior
to the first dose of trial treatment and any neurologic symptoms have returned to
baseline), have no evidence of new or enlarging brain metastases, and are not using
systemic steroids for at least 7 days prior to trial treatment. This exception does
not include carcinomatous meningitis which is excluded regardless of clinical
stability
13. Has a history of interstitial lung disease, pneumonitis within 12 months prior to
screening or current pneumonitis
14. Has an active infection requiring systemic therapy
15. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator
16. Has a history or ongoing clinically significant cardiovascular disease such as
unstable angina, myocardial infarction, or acute coronary syndrome, symptomatic or
uncontrolled arrhythmia, congestive heart failure, baseline ECG abnormalities,
including, but not limited to, QTc prolongation (prolonged QTcF defined as =450 msec)
or any Class III or IV cardiac disease as defined by the New York Heart Association
Functional Classification
17. Has overt or latent disorders of the exocrine pancreas (such as acute or chronic
pancreatitis of any etiology) or chronic (including autoimmune) gastrointestinal
disorders such as Crohn's disease, ulcerative colitis, rheumatoid arthritis, lupus,
scleroderma, Sjogren's syndrome, and polyarteritis nodosa
18. Has a known psychiatric or substance abuse disorder(s) that would interfere with
informed consent or cooperation with the requirements of the trial
19. Is pregnant or breastfeeding or expecting to conceive children within the projected
duration of the trial, starting with the prescreening or screening visit through 90
days after the last dose of study drug
20. Is a first degree relative of the investigator, staff, or study sponsor.
|
