This is a first-in-human (FIH), open-label, phase 1 dose-escalation study of 609A, a
recombinant monoclonal anti-PD-1 antibody product, in subjects with Locally
advanced/Metastatic Solid Tumors, who must have received, or be intolerant to all available
approved or standard therapies known to confirm clinical benefit, or for whom no standard
therapy exits.
Inclusion Criteria:
Subjects must meet all the following inclusion criteria to be eligible for participation in
this study:
- Able to understand and willing to sign the Informed Consent Form(ICF).
- Male or female ≥ 18years.
- Subjects with histologically or cytologically confirmed advanced-stage or metastatic
tumor must have received, or be intolerant to all available approved or standard
therapies known to confirmed clinical benefit, or for whom standard therapy does not
exist.
- Must have adequate organ function, prior to start of 609A, including the following:
1. Bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.0 ×109/L; platelet
count≥ 100 × 109/L; hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L;
2. Hepatic: total bilirubin ≤ 1.5 times the upper limit of normal (ULN), aspartate
transaminase (AST) and/or alanine aminotransferase (ALT) ≤ 3 × ULN (≤5 × ULN if
with liverinvolvement)
3. Renal: serum creatinine ≤1.5 times the ULN or estimated creatinineclearance
≥50mL/min (Cockroft and Gault formula
[http://www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation/]).
4. Coagulation tests INR≤ 2 (Exception: INR 2 to ≤ 3 is acceptable for subjects
onWarfarin anticoagulation), activated partial thromboplastin time (aPTT) ≤ 1.5 ×
ULN
- Regarding prior anti-tumortherapy:
1. Subjects who have received any anticancer drugs approved or investigational,
including chemotherapy, immune therapy, hormonal therapy (Exceptions:
hormone-replacement therapy, testosterone or oral contraceptives), biologic
therapy, must have stopped treatment at least 3 weeks, or five half-lives,
whichever is shorter, before first dose of 609A.
2. Generalized radiation therapy must have stopped 3 weeks before first dose of
609A, or local radiotherapy or radiation therapy for bone metastases must have
stopped 2 weeks before first dose of 609A. No therapeutic radiopharmaceuticals
are taken within 8 weeks before first dose of 609A.
3. Subjects who have received prior immunotherapies targeting T cell stimulation
such as (e.g. anti-PD-1, anti- PD-L1 or anti-CTLA-4) must have stopped treatment
for at least 4 weeks before first dose of 609A.
- Female patient with fertility or male patient whose partner has fertility should use
one or more contraceptive methods for contraception from the screening period to five
half-lives after the last treatment. These measures include, but are not limited to,
oral or implantable injections of hormonal contraceptives; intrauterine birth control
ring or placement of intrauterine system (IUS) hormone-releasing intrauterine device;
or use of barrier methods such as condoms or septum and spermicide products. Women of
childbearing potential must have a negative pregnancy test ≤ 72 hours prior to the
first dose of study drug.
Postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of
non-childbearing potential.
- According to RECIST1.1, the subject should have an assessable lesion (target lesion or
non- target lesion)
- According to RECIST1.1, the subject should have an assessable lesion (target lesion or
non- target lesion) ECOG score 0, 1 or 2 point.
Exclusion Criteria:
- Subjects who meet any of the following criteria cannot be enrolled: Life expectancy <
3 months.
- Any remaining AEs > grade 1 from prior anti-tumor treatment as per CTCAE v5. 0, with
exception of the residual hair loss;
- Any remaining AEs > grade 1 from prior anti-tumor treatment as per CTCAE v5. 0, with
exception of the residual hair loss; Any involvement of CNS excluded except: Based on
screening brain magnetic resonance imaging (MRI), patients must have one of the
following:
1. No evidence of brain metastases or has to be clinically stable for at least 4
weeks
2. Untreated brain metastases not needing immediate localtherapy
- Pregnant or nursing females
- Subjects who have had major surgery within the 21-days from the screening;
- Subjects with history of interstitial lung disease or idiopathic pulmonary fibrosis or
unresolved active or chronic inflammatory pulmonary disease are excluded. Subjects
with a history of radiation pneumonitis which has resolved areeligible.
- HIV infection.
- Active hepatitis B or C. HBV carriers without active disease (HBV DNA titer< 1000
cps/mL or 200 IU/mL) or cured Hepatitis C (negative HCV RNA test) may been rolled.
- History of primary immunodeficiency, stem cell or organ transplant, or previous
clinical diagnosis of tuberculosisdisease.
- History of life-threatening hypersensitivity or known to be allergic to protein drugs
or recombinant proteins or excipients in 609A drug formulation.
- Acute or chronic uncontrolled renal disease, pancreatitis or liver disease (per
investigator assessment).
- Subjects with any type of primary immunodeficiencies will be excluded from thestudy.
- Subjects with condition requiring systemic treatment with either corticosteroids (>15
mg/day prednisone or equivalent) or other immunosuppressive medications within 14 days
before the planned first dose of study drug. Inhaled or topical steroids, and adrenal
replacement steroid doses ≤ 10 mg daily prednisone equivalent are permitted in the
absence of activeautoimmune disease. Ophthalmologic, nasal and intra-articular
injections of steroids areacceptable.
- Subjects who experienced immunotherapy-related adverse events (irAE) grade ≥ 3, or who
had to discontinue prior anti-PD-1, anti-PD-L1, or CTL4 treatment due to irAEs of any
grade.
- Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure
NYHA III or IV, unstable angina pectoris even if medically controlled, history of
myocardial infarction during the last 6 months, ECG QTcF (Fridericia)≥450 msec for
male or QTcF (Fridericia)≥470 msec for female, serious arrhythmias requiring
medication (with exception of atrial fibrillation or paroxysmal supraventricular
tachycardia).
- Hypertension (defined as sustained systolic blood pressure> 160 mm Hg and / or post-
diastolic blood pressure with antihypertensive drugs> 100 mmHg;
- Any other serious underlying medical (e.g. uncontrolled diabetes mellitus, active
uncontrolled infection, active gastric ulcer, uncontrolled seizures, cerebrovascular
incidents, gastrointestinal bleeding, severe signs and symptoms of clotting
disorders), psychiatric, psychological, familial or geographical condition that, in
the judgment of the investigator, may interfere with the planned staging, treatment
and follow-up, affect subject compliance or place the subject at high risk from
treatment-related complications.
- Has received a live and attenuated vaccine within 28 days prior to the first dose of
study drug.
- Patients who had received treatment with any herbal or alternative therapies or
Chinese prepared medicine within 7 days prior to the first dose of the studydrug.
- Subjects with active autoimmune diseases or history of autoimmune diseases should be
excluded; these include but are not limited to subjects with a history of immune
related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy,
Guillain- Barre syndrome, myasthenia gravis, systemic lupus erythematosus (SLE),
connective tissue diseases, scleroderma, inflammatory bowel disease including Crohn's
disease and ulcerative colitis, hepatitis, toxic epidermal necrolysis (TEN),
Stevens-Johnson syndrome, or antiphospholipidsyndrome.
