Non-Small Cell Lung Cancer, Colorectal Cancer, Renal Cell Carcinoma, Melanoma and Other Solid Tumor
Conditions
Brief summary
The purpose of this phase I clinical study was to evaluate the safety and tolerability of AWT020 monotherapy and combination with other antitumor therapies in patients with advanced malignancies
Interventions
DRUGCapecitabine
1000 mg/m2, BID, day1-14, oral, q3w
DRUGBevacizumab
7.5 mg/kg, Q3W
DRUGRenvastinib
8mg or 20mg, QD
DRUGAWT020
q3w or q2w, i.v.
DRUGTaxol
135\ 175 mg/m2, Q3W
Cisplatin(75 mg/m2, Q3W) or Carboplatin (AUC=5\ 6, Q3W)
DRUGPemetrexed
500 mg/m2, Q3W
DRUGOxaliplatin
130 mg/m2, Q3W
Sponsors
Shanghai Junshi Bioscience Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Both male and female subjects who are at least 18 years old at the time of signing the consent form; 2. Inclusion of patients with advanced malignancies confirmed histologically or cytologically and meeting the following requirements: * Single-agent dose escalation and expansion phase to include patients with advanced malignant tumors who have failed or are intolerant of standard treatment, or have no standard treatment options; * Therapeutic effect expansion stage of single drug: 1. NSCLC: histologically or cytologically confirmed, unresectable locally advanced, relapsed, or distant metastatic NSCLC that has progressed after prior treatment with PD-(L)1 antibody and platinum-containing chemotherapy (except after the last dose > Progression of adjuvant and neoadjuvant therapy within 6 months). Subjects with EGFR or ALK mutations will need to progress with prior treatment with appropriate kinase inhibitors. 2. Melanoma: histologically unresectable stage III or IV melanoma that has progressed after prior chemotherapy and treatment with PD-(L)1 inhibitors (except after the last dose > Adjuvant and neoadjuvant therapy that progresses within 6 months); Mucosal melanoma does not require prior PD-(L)1 inhibitor therapy. 3. CRC: colorectal adenocarcinoma or rectal adenocarcinoma with histologically confirmed PD-L1 composite positive score \[CPS\] ≥1, failure or intolerance of standard treatment, or no standard treatment options. PD-L1 expression levels in tumor tissues are based on the results of the central laboratory tests designated by the sponsor (the inclusion criteria for PD-L1 expression levels can also be adjusted according to previous data during the study). 4. RCC: Histologically confirmed metastatic or unresectable clear cell type of RCC with disease progression after previous treatment with targeted anti-angiogenesis therapy and PD-(L)1 inhibitors. 5. Other advanced malignancies: patients with advanced malignancies who have failed or been intolerant to standard treatment or have no standard treatment options. * Combination phase: 1. NSCLC: histologically or cytologically confirmed, unresectable locally advanced, relapsed, or distant metastatic NSCLC that has not progressed after prior treatment with PD-(L)1 antibody and platinum-containing chemotherapy (except after the last dose > Progression of adjuvant and neoadjuvant therapy within 6 months). Subjects carrying EGFR or ALK mutations were allowed to progress on kinase inhibitor therapy with a previous ≤1 line. 2. CRC: Histologically confirmed PD-L1 CPS≥1 colorectal adenocarcinoma or rectal adenocarcinoma without prior systemic therapy (except after the last dose of medication > Adjuvant therapy that progresses within 6 months); In patients with MSI-H/dMMR, previous treatment with PD-(L)1 inhibitors is permitted. PD-L1 expression levels in tumor tissues are based on the results of the central laboratory tests designated by the sponsor (the inclusion criteria for PD-L1 expression levels can also be adjusted according to previous data during the study). 3. RCC: Histologically confirmed metastatic or unresectable clear cell RCC with disease progression after previous treatment with anti-angiogenesis targeted therapy and PD-(L)1 inhibitors. 4. Melanoma: histologically unresectable stage III or IV melanoma that has progressed after prior chemotherapy and treatment with PD-(L)1 inhibitors (except after the last dose > Adjuvant therapy that progresses within 6 months). 5. HCC: Histologically/cytologically confirmed or cirrhotic patients meet the clinical diagnostic criteria for HCC in AASLD, are identified as having stage B (intermediate) or stage C (advanced) BCLC HCC and are not candidates for radical surgery and/or local therapy, and have previously received PD-(L)1 inhibitors and anti-angiogenic targeted therapy progression. 6. Other advanced malignancies: patients with advanced malignancies who have failed or been intolerant to standard treatment, or have no standard treatment options. 3. ECOG score is 0 or 1; 4. Expected survival ≥12 weeks; 5. Have at least one measurable lesion according to RECIST 1.1 evaluation criteria; 6. Good organ function; 7. Fertile female or male subjects must agree to be childfree during the study period until 6 months after the end of the last dose and voluntarily take highly effective contraception with their partner; The serum pregnancy test for WOCBP must be negative within 7 days prior to the first dose and must be non-lactation (specific contraceptive methods and WOCBP definitions are set out in section 10.3); 8. Patients participate voluntarily, give full informed consent, sign written informed consent, and have good compliance.
Exclusion criteria
1. Received the following drugs or treatments before the first dose: 1. received chemotherapy, immunotherapy and other anti-tumor therapy or other investigational drugs within 21 days before the first dose, or received oral fluorouracil, small molecule targeted drugs or Chinese medicines with anti-tumor indications within 14 days before the first dose; 2. Major surgery or radiotherapy within 28 days before the first dose (palliative radiotherapy for local bone/brain lesions allowed within 14 days before the first dose), coarse needle puncture biopsy or other minor surgery within 7 days before the start of study therapy, excluding placement of vascular infusion devices; 3. In combination therapy, patients who have been systematically treated with corticosteroids (\> 10 mg prednisone per day or equivalent) or other immunosuppressants for more than 1 week within 2 weeks prior to initial administration are allowed to be treated with inhaled or topical steroids or ≤10 mg/ day systemic prednisone and equivalent doses of similar drugs; 2. There is active central nervous system metastasis. If the patient has received radiotherapy or surgery in the past, imaging examination within 4 weeks before the first medication indicates stable brain metastases without aggravation or new neurological symptoms, hormone therapy has been discontinued 2 weeks before the first medication, and screening is allowed; For meningeal and brainstem metastases, screening is not allowed regardless of treatment. 3. Immune-related adverse events that led to permanent discontinuation occurred during previous immunosuppressive therapy (such as anti-PD -(L)1, CTLA-4, LAG-3 inhibitors, etc.); 4. There are pleural effusion, abdominal effusion or pericardial effusion with clinical symptoms that require repeated treatment (puncture or drainage, etc.); 5. There is a history of interstitial lung disease or a history of non-infectious pneumonia treated with corticosteroids, or imaging evidence of active pneumonia during the screening period; 6. The presence of severe, unhealed or split wounds, active ulcers, or untreated fractures (other than old fractures assessed by the investigator without clinical intervention); 7. Obvious bleeding tendency or severe coagulation dysfunction; 8. Have poorly controlled hypertension (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure \> 100 mmHg), or have a history of hypertensive crisis or hypertensive encephalopathy; 9. The toxicity of previous antitumor therapy did not return to the level ≤ Class 1 prescribed by CTCAE v5.0 or the level specified by the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DLT rate | Up to approximately 12 months from first patient in | DLT rate |
| AE | Up to approximately 12 months from first patient in | Safety endpoint: incidence and severity of AE, abnormal changes in clinically significant laboratory and other tests |
| SAE | Up to approximately 12 months from first patient in | Safety endpoint: incidence and severity of SAE, abnormal changes in clinically significant laboratory and other tests |
| MTD | Up to approximately 12 months from first patient in | Determine maximum tolerated dose |
| RP2D | Up to approximately 32 months from first patient in | Recommended phase II dose (RP2D) for AWT020 monotherapy and combination therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS | Up to approximately 32 months from first patient in | Efficacy endpoint: Progress -free survival (PFS) per RECISIT v1.1 |
| Drug concentrations | Up to approximately 24 months from first patient in | Drug concentrations in individual subjects at different time points after dosing |
| OS | Up to approximately 32 months from first patient in | Efficacy endpoint: Overall survival (OS) |
| Immunogenicity | Up to approximately 24 months from first patient in | Incidence of anti-drug antibody (ADA) and/or neutralizing antibody (Nab), titer of ADA positive samples |
| ORR | Up to approximately 32 months from first patient in | Efficacy endpoint: Objective response rate(ORR) per RECIST v1.1 |
| DOR | Up to approximately 32 months from first patient in | Efficacy endpoint: Duration of response (DOR) per RECISIT v1.1 |
| DCR | Up to approximately 32 months from first patient in | Efficacy endpoint: Disease control rate (DCR) per RECISIT v1.1 |
Countries
China
Contacts
Primary ContactXiaohong Ding, Master
Outcome results
None listed