Phase 1, First in Human, Open-Label, Dose-Escalation Study of 609A in the Patients with
Locally advanced/Metastatic Solid Tumors in China.
This is a first-in-human (FIH), open-label, phase 1 dose-escalation study of 609A in China, a
recombinant monoclonal anti-PD-1 antibody product, in subjects with Locally
advanced/Metastatic Solid Tumors, who must have failed standard treatment (disease
progression or intolerance) or lack of standard treatment. If there is a driver gene variant,
the subjects must have failed the standard treatment for the driver gene, and there is no
other standard treatment.
Subjects must meet all the following inclusion criteria to be eligible for participation in
- Able to understand and willing to sign the Informed Consent Form(ICF).
- No limit gender .
- Age range: from 18 years to 70 years.
- Subjects with histologically or cytologically confirmed locally advanced-stage or
metastatic tumor must have failed standard treatment (disease progression or
intolerance) or lack of standard treatment. If there is a driver gene variant, the
subjects must have failed the standard treatment for the driver gene, and there is no
other standard treatment.
- Patients who had been previously treated for brain metastases, must have asymptomatic
or radiographic/clinical stability and no need for steroid therapy of brain metastases
to be enrolled in this study within 4 weeks prior to enrollment .
- According to RECIST1.1, Patients must have at least one measurable lesion (target or
- ECOG scores 0,1 or 2.
- Life expectancy ≥3 months
- 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
3. Renal: serum creatinine ≤1.5 times the ULN or estimated creatinineclearance
≥50mL/min (Cockroft and Gault formula).
4. Coagulation tests INR≤ 2 (Exception: INR 2 to ≤ 3 is acceptable for subjects on
Warfarin anticoagulation), activated partial thromboplastin time (aPTT) ≤ 1.5 ×
- 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.
Subjects who meet any of the following criteria will not be enrolled:
- History of life-threatening hypersensitivity or known to be allergic to protein drugs
or recombinant proteins or excipients in 609A drug formulation.
- Subjects who had experienced severe allergic reactions after administration of other
- Pregnant or nursing females
- Regarding previous anti-tumor therapy:
1. Subjects who have received any anticancer drugs approved or investigational,
including chemotherapy,hormonal therapy (Exceptions: hormone-replacement therapy,
testosterone or oral contraceptives), biologic therapy, have stopped treatment
for less than 3 weeks or 5 half-lives, whichever is longer, before first dose of
2. Subjects who have stopped systemic radiation therapy less than 3 weeks before
first dose of 609A, or local radiotherapy or radiation therapy for bone
metastases less than 2 weeks before first dose of 609A. Therapeutic
radiopharmaceuticals were 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) ,have stopped treatment less
than 3 months before first dose of 609A.
4. The ADA antibody of anti-PD-1 drug in plasma was positive during screening.
5. Subjects who have received immunogonists (such as interleukin-2 gamma interferon,
oncolytic virus, mistletoe extract, etc.) or drugs known to interfere with major
organ function (e.g., hypericin) , have stopped treatment less than 4 weeks or 5
half-lives, whichever is longer, before first dose of 609A.
- Subjects with severe chronic or active infections requiring systemic antimicrobial,
antifungal, or antiviral treatment, including tuberculosis.
- 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
- Subjects with history of interstitial lung disease or noncommunicable pneumonia, or
uncontrolled pulmonary fibrosis or acute pulmonary disease . Local interstitial
pneumonia due to radiotherapy was excluded.
- Acute or chronic uncontrolled renal disease( Exception: Renal carcinoma, metastatic
renal cancer), pancreatitis or liver disease (per investigator assessment).
- Any remaining AEs > grade 1 from prior anti-tumor treatment as per CTCAE v5. 0, with
exception of the residual hair loss.
- Any SAE occurred during previous pd-1 / pd-l1 treatment, including but not limited to
interstitial pneumonia and myocarditis.
- 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
- Subjects with acute myocardial infarction, unstable angina pectoris, stroke, or
transient ischemic attack occurred within 6 months prior to admission. Subjects with
congestive heart failure rated as grade 2 or above (including grade 2) by the New York
college of cardiology (NYHA) ,LVEF<50%.And subjects with the following heart diseases:
1. ECG QTcF> 480 msec during screening.
2. Right bundle branch block and left anterior half branch block or complete left
bundle branch block.
3. Subjects with congenital long QT syndrome or a family history of unexpected
sudden cardiac death.
4. Subjects with ventricular tachyarrhythmia or history of tachyarrhythmia.
5. Bradycardia with obvious clinical significance (< 50 times/min).
6. Subjects using pacemakers.
7. Subjects with other heart disease with significant clinical significance.
- Sustained systolic blood pressure >160 mm Hg and/or diastolic blood pressure >100 mm
Hg after antihypertensive medication.
- Fever and neutropenia occurred within 1 week before the first dose of 609A.
- Subjects who have had major surgery within 21 days before the first dose of 609A
((excluding diagnostic biopsies).
- Live attenuated vaccines were administered within 28 days before the first dose of
- Patients who had received treatment with any herbal or alternative therapies or
Chinese prepared medicine within 7 days before the first dose of 609A.
- History of primary immunodeficiency, stem cell or organ transplant, or previous
clinical diagnosis of tuberculosis disease.
- 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 antiphospholipid syndrome.
- 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 active autoimmune disease. Ophthalmologic, nasal and intra-articular
injections of steroids are acceptable.
- 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
- Any other conditions not suitable for subjects to be enrolled in this study, as
determined by the investigator.