Study of KN046 in Subjects With Advanced Non-Small Cell Lung Cancer

NCT05420220 | Recruiting Phase 2 DMC

• 1 other identifier: KN046-209
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 6

Brief Summary

This is an open-label, multi-center, Phase 2 study in subjects with treatment-naïve locally advanced (unresectable and unable to receive radical chemoradiotherapy) or metastatic PD-L1-positive non-small cell lung cancer (NSCLC) who have received systemic therapy.

Conditions

Advanced Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  defined as the proportion of subjects with a confirmed best overall response (BOR) of CR or PR per RECIST v1.1 as assessed by the investigator.

  Up to 2 years

Secondary Outcomes (7)

• Duration of response (DOR)

  Up to 2 years

• Disease control rate (DCR)

  Up to 2 years

• Clinical benefit rate (CBR),

  Up to 2 years

• Time to response (TTR)

  Up to 2 years

• Progression-free survival (PFS)

  Up to 2 years

Study Arms (1)

KN046+Axitinib

EXPERIMENTAL

Eligible subjects will receive KN046 5 mg/kg Q3W IV in combination with Axitinib 5 mg bid po, until progressive disease as judged by the investigator per RECIST v1.1

Biological: KN046 (Recombinant Humanized PD-L1/CTLA-4 Bispecific Single Domain Antibody Fc Fusion Protein Injection); Combination Product: Axitinib

Interventions

KN046 (Recombinant Humanized PD-L1/CTLA-4 Bispecific Single Domain Antibody Fc Fusion Protein Injection) BIOLOGICAL

5 mg/kg Q3W IV

KN046+Axitinib

Axitinib COMBINATION_PRODUCT

5mg bid po

KN046+Axitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• I01. Subjects who are able to understand the Informed Consent Form (ICF) and sign the ICF;
• I02. Male or female subjects, aged 18 years or older; willing and able to complete all required study procedures;
• I03. Subjects with histologically or cytologically confirmed locally advanced (stage IIIB/IIIC) and stage IV (defined by the Union for International Cancer Control and the American Joint Committee on Cancer Staging System, edition 8) non-small cell lung cancer that is unresectable and unable to receive radical chemoradiotherapy;
• I04. Subjects who are PD-L1+ (TPS ≥ 1%) confirmed by central laboratory;
• I05. Subjects who must have negative EGFR mutation and ALK translocation (testing is not mandatory for subjects with squamous cell carcinoma whose EGFR/ALK gene mutation status is unknown). Subjects with known driver genes for other approved targeted drug therapies are also not eligible.
• I06. Subjects who have not received systemic therapy for locally advanced/metastatic NSCLC. Subjects who have received prior neoadjuvant, adjuvant chemotherapy, or radical chemoradiotherapy are allowed if they develop progressive disease at least 6 months after completing the aforementioned treatment;
• I07. Subjects with at least one measurable lesion per RECIST v1.1 at baseline;
• I08. Subjects with a ECOG score of 0 or 1;
• I09. Subjects with adequate organ function assessed within 7 days prior to first trial treatment as follows:
• Hematology (without transfusion or use of hematopoietic stimulators within 14 days prior to enrollment)
• ANC≥1.5 × 109/L;
• Hemoglobin ≥ 9 g/dL;
• Platelets ≥ 100 × 109/L;
• White blood cell count (WBC) ≥ 4.0 × 109/L and ≤ 15 × 109/L;
• Renal function

You may not qualify if:

• E01. Subjects with untreated metastases to central nervous system. Subjects with a previous diagnosis of metastases to central nervous system are eligible to enroll if they have completed treatment, have been clinically stable (assessed by imaging, preferably MRI with contrast-enhanced MRI or CT) for at least 2 weeks, and their neurological and other clinical symptoms have recovered to ≤ Grade 1 per NCI-CTC AE at least 2 weeks before the first dose, and steroids for brain metastases are discontinued 7 days prior to the first dose of trial treatment.
• E02. Subjects who have received prior immune checkpoint inhibitors, including but not limited to anti-PD-1, PD-L1, CTLA-4, LAG3 agent or other immune checkpoint inhibitors; Subjects who have received prior treatment with single/multi-target inhibitors or monoclonal antibodies to VEGF or VEGFR signaling pathways;
• E03. Subjects who have undergone major surgery for any reason within 4 weeks prior to the first dose of trial treatment;
• E04. Subjects who have a history of radiotherapy that meets the following criteria and fail to recover from toxicity/complications of radiotherapy to ≤ Grade 1 per NCI-CTCAE (except alopecia and fatigue)
• Thoracic radiotherapy: subjects who have received a chest radiation dose of \> 30 Gy within 24 weeks before the first dose;
• Non-thoracic radiotherapy: subjects who have received a non-thoracic radiotherapy with a dose of \> 30 Gy within 4 weeks before the first dose.
• Subjects who have received palliative radiotherapy with a dose of ≤ 30 Gy within 2 weeks before the first dose; Palliative radiotherapy for symptom control is permitted and must be completed at least 2 weeks before the start of study drug.
• E05. Subjects who have participated in a study or received the treatment with other investigational drugs within 4 weeks or less than 5 times of half-life (not less than 2 weeks), whichever is shorter prior to the first dose of trial treatment;
• E06. Subjects who have received treatment with anti-tumor vaccines, anti-tumor traditional Chinese medicine or other anti-tumor drugs with immunostimulatory effects within 2 weeks prior to the first dose;
• E07. Subjects who require systemic corticosteroids (≥ 10 mg/day prednisone or equivalent dose of other corticosteroids) or immunosuppressive therapy for 7 consecutive days within 14 days prior to the first dose; except inhaled or topical corticosteroids, or physiologic replacement doses of corticosteroids for adrenal insufficiency; short-term (≤ 7 days) corticosteroids are allowed for prophylaxis (e.g., contrast media allergy) or for the treatment of non-autoimmune disorders (e.g., delayed-type hypersensitivity reactions due to contact allergens);
• E08. Subjects who have received vaccination within 28 days prior to the first dose of trial treatment, except for inactivated vaccines.
• E09. Subjects who have interstitial lung disease, or a history of pneumonia requiring oral or intravenous corticosteroids to assist in management;
• E10. Subjects with uncontrolled hypertension (blood pressure ≥ 150/95 mmHg at rest) after standard antihypertensive therapy.
• E11. Subjects who have a history of or current autoimmune diseases, including, but not limited to, Crohn's disease, ulcerative colitis, systemic lupus erythematosus, sarcoidosis, Wegener's syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis), autoimmune hepatitis, systemic sclerosis (scleroderma, etc.), Hashimoto's thyroiditis (refer to the following exceptions), autoimmune vasculitis, autoimmune neuropathy (Guillain-Barre syndrome).
• E12. Subjects who have other malignancies within 5 years before the first dose, except cured skin squamous cell carcinoma, basal cell carcinoma, non-muscle invasive bladder cancer, localized low-risk prostate cancer (defined as stage ≤ T2a, Gleason score ≤ 6, and PSA ≤ 10 ng/mL (as measured) at diagnosis of prostate cancer, the subjects had received curative treatment and no prostate-specific antigen (PSA) biochemical recurrence), and in-situ cervical/breast cancer;

Sponsors & Collaborators

• Jiangsu Alphamab Biopharmaceuticals Co., Ltd: lead

Study Sites (6)

The Second Hospital of Anhui Medical University

Hefei, Anhui, China

RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

RECRUITING

Linyi Cancer Hospital

Linyi, Shandong, China

RECRUITING

Yantai Yuhuangding Hospital

Yantai, Shandong, China

RECRUITING

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, China

NOT YET RECRUITING

The first affiliated hospital, Zhejiang university

Hangzhou, Zhejiang, China

NOT YET RECRUITING

MeSH Terms

Interventions

Axitinib

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Li Zhang, Doctor

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Li Zhang, Doctor

CONTACT

86-13902282893; zhangli@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2022
• First Posted: June 15, 2022
• Study Start: July 15, 2022
• Primary Completion (Estimated): May 29, 2027
• Study Completion (Estimated): December 26, 2027
• Last Updated: May 1, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)