A Study of Anti-PD-1 AK105 in Patients With Metastatic Nonsquamous Non-small Cell Lung Cancer

Akeso

Status and phase

Terminated

Phase 3

Conditions

Lung Cancer Non-small Cell Stage IV

Treatments

Biological: AK105

Drug: carboplatin

Drug: placebo

Drug: Anlotinib

Drug: pemetrexed

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT03866980

AK105-301

Details and patient eligibility

About

This is a phase III , randomized, double-blinded, multicenter clinical study to compare efficacy and safety of AK105 (Anti-PD1 antibody) combined with Carboplatin and Pemetrexed vs Placebo combined with Carboplatin and Pemetrexed as first-line therapy in patients with EGFR and ALK wild type metastatic nonsquamous non-small cell lung cancer.

Enrollment

164 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

164 participants in 3 patient groups, including a placebo group

AK105 plus Carboplatin and Pemetrexed

Experimental group

Description:

Subjects receive AK105 200 mg intravenously (IV) plus pemetrexed 500 mg/m\^2 IV and carboplatin area under the curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by AK105 200 mg IV plus pemetrexed 500 mg/m\^2 IV Q3W until progression.

Treatment:

Drug: carboplatin

Drug: pemetrexed

Biological: AK105

Placebo plus Carboplatin and Pemetrexed

Placebo Comparator group

Description:

Subjects receive placebo intravenously (IV) plus pemetrexed 500 mg/m\^2 IV and carboplatin area under the curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by AK105 200 mg IV plus pemetrexed 500 mg/m\^2 IV Q3W until progression.

Treatment:

Drug: placebo

Drug: carboplatin

Drug: pemetrexed

AK105 plus anlotinib

Experimental group

Description:

Subjects receive AK105 200 mg intravenously (IV) plus Anlotinib 12mg/d PO D1-14, Q3W until progression.

Treatment:

Drug: Anlotinib

Biological: AK105