| Eligibility |
Inclusion Criteria:
- Signed written informed consent form voluntarily.
- Age over 18 years old (inclusive) and not more than 75 years old (inclusive), when
signing the ICF.
- Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
- Expected life expectance = 3 months.
- Histologically or cytologically confirmed diagnosis of stage IV nonsquamous NSCLC.
- No prior systemic chemotherapy for advanced or metastatic NSCLC. Subjects who have
received prior adjuvant chemotherapy or neoadjuvant chemotherapy with curative intent,
or definitive chemoradiotherapy for advanced disease, will be eligible provided that
progression has occurred >6 months from last treatment.
- At least one measurable tumor lesion per RECIST 1.1 criteria. A lesion previously
irradiated will not be considered a target lesion.
- Subjects must provide an available tumor tissue sample taken < 12 months prior to
first dose of study treatment.
- Subjects must provide wild-type EGFR and ALK reported by tissue-based tests. For
subjects without documented wild-type EGFR/ALK, archival or fresh tumor tissues are
required for EGFR/ALK assessment prior to enrollment.
- Adequate organ function.
- Females of childbearing potential who are sexually active with a nonsterilized male
partner must use at least one highly effective method of contraception.
- Nonsterilized males who are sexually active with a female partner of childbearing
potential must use highly effective method of contraception from Day 1 and for 120
days after the last dose of investigational product.
Exclusion Criteria:
- Subjects who are diagnosed as NSCLC that harbors an EGFR-sensitizing mutation or ALK
gene translocation.
- Subjects with other histological types of NSCLC, including mixed squamous cell
carcinoma and adenocarcinoma, and mixed carcinoma containing small cell lung carcinoma
or neuroendocrine carcinoma.
- Received prior treatment with EGFR inhibitors or ALK inhibitors.
- Receipt of last radiotherapy or any anti-tumor treatment [chemotherapy, targeted
therapy, immunotherapy, Chinese patent drugs with antitumor indications, or
immunomodulators or tumor embolization] within 3 weeks prior to the first dose of
study treatment.
- Prior exposure to any anti-PD-1, anti-PD-L1, anti-CTLA-4 antibody, or any other
antibody or drug therapy for T cell co-stimulatory or checkpoint pathways, such as
ICOS or agonists (e.g. CD40, CD137, GITR and OX40 etc).
- Other invasive malignancies within 5 years, except for locally treatable (manifested
as cured) malignancies, such as basal or skin squamous cell carcinoma, superficial
bladder cancer, cervical or breast carcinoma in situ.
- Subjects with active, known or suspected autoimmune disease, or a medical history of
autoimmune disease, with the exceptions of the following: vitiligo, alopecia, Grave
disease, psoriasis or eczema not requiring systemic treatment within the last 2 years,
hypothyroidism (caused by autoimmune thyroiditis) only requiring steady doses of
hormone replacement therapy and type I diabetes only requiring steady doses of insulin
replacement therapy, or completely relieved childhood asthma that requires no
intervention in adulthood, or primary diseases that will not relapse unless triggered
by external factors.
- Active or previously documented inflammatory bowel disease (e.g. Crohn's disease,
ulcerative colitis or chronic diarrhea).
- Subjects who require systemic corticosteroids (a dose equivalent to >10 mg/day
prednisone) or other immunosuppressive drugs within 14 days prior to the first dose of
study drug.
- Major surgery (as defined by the investigator) within 28 days prior to the first dose
of study drug.
- Subjects who received non-thoracic radiotherapy >30 Gy within 4 weeks prior to the
first dose, or thoracic radiotherapy >30 Gy within 24 weeks prior to the first dose
study drug.
- History of gastrointestinal perforation and/ or fistula within 6 months prior to the
first dose of study drug.
- Known history of primary immunodeficiency virus infection.
- Known history of allogeneic organ transplantation or allogeneic hematopoietic stem
cell transplantation.
- Known history of interstitial lung disease.
- Known history of active tuberculosis (TB).
- An active infection requiring systemic therapy.
- Subjects with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) DNA
exceeding 500 IU/ mL or active hepatitis C virus (HCV) should be excluded. Subjects
with non-active HBsAg carriers, treated and stable hepatitis B (HBV DNA <500 IU/ mL) ,
and cured hepatitis C can be enrolled. Subjects with positive HCV antibodies are
eligible only if the HCV RNA test results are negative.
- Known history of testing positive for human immunodeficiency virus (HIV).
- Presence of meningeal metastasis, spinal cord compression, leptomeningeal disease or
active brain metastasis.
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated
drainage.
- Clinically active hemoptysis, active diverticulitis, peritoneal abscess, or
gastrointestinal obstruction.
- Clinically significant bleeding symptoms or significant bleeding tendency such as
gastrointestinal bleeding, hemorrhagic gastric ulcer or vasculitis within 1 month
prior to the first dose of study treatment.
- Unresolved toxicities from prior anticancer therapy, defined as having not resolved to
NCI CTCAE v5.0 Grade 0 or 1, or to levels dictated in the inclusion/exclusion
criteria, with the exception of alopecia.
- Receipt of live or attenuated vaccination within 30 days prior to the first dose of
study treatment, or plan to receive live or attenuated vaccine during the study.
- Known history of server hypersensitivity to other monoclonal antibodies.
- Known severe allergic reactions to anlotinib,pemetrexed, carboplatin or
platinum-containing component, or their preventive medications.
- Known allergic reactions to any ingredients of AK105.
- Pregnant or lactating women.
- Any conditions that, in the investigator's opinion, may put subjects treated with the
study drug at risks, or interfere with the evaluation of study drug or subject safety,
or the interpretation of study results.
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