Patients with malignant solid tumors confirmed by histology or cytology
Conditions
Interventions
Part A:SHR-4849 combined with SHR-1316
Part B:SHR-4849 combined with SHR-1316 and SHR-8068
Part C:SHR-4849 in combination with SHR-1316 and BP102
Part D:SHR-4849 in combination with SHR-1316, BP102 and SHR-8068
Part E:SHR-4849 combined with BP102
Part F:SHR-4849 combined with SHR-1316 and carboplatin or cisplatin
Part G:SHR-4849 combined with SHR-1316, carboplatin or cisplatin and SHR-8068
Part H:SHR-4849 combined with SHR-1316, carboplatin or cisplatin and BP102
Sponsors
Shandong Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria to enter this study: 1. Voluntarily participate in this clinical study, understand the research procedures and be able to sign the informed consent form in person; 2. Age: 18 to 75 years old (inclusive), gender not limited. 3. Patients with solid tumors that have been histologically or cytologically confirmed as inoperable (as detailed below) : Phase One: Dose Exploration Phase Part A/B/C/D/E: Patients with recurrent or metastatic small cell lung cancer, large cell neuroendocrine carcinoma of the lung, or other neuroendocrine carcinomas who have progressed after at least standard treatment in the past. The previous systemic chemotherapy has not exceeded two lines. 2) Part F/G/H: Patients with relapsed or metastatic extensive-stage small cell lung cancer, large cell neuroendocrine carcinoma of the lung, and other neuroendocrine carcinomas who have progressed after only one line of standard treatment in the past. Patients who have received platinum-based chemotherapy are required to have more than 90 days from the last platinum-based chemotherapy to the onset of disease progression. Phase Two: The stage of expanding therapeutic effects Small cell lung cancer (SCLC), cohort A1/B1/C1/D1/E1: Patients with recurrent or metastatic small cell lung cancer who have progressed after <=2 lines of standard treatment. Cohort F1/G1/H1: Patients with relapsed or metastatic extensious-stage small cell lung cancer who have progressed after <=1 line of standard treatment and have received platinum-based chemotherapy are required to have a time from the last platinum-based chemotherapy to disease progression exceeding 90 days. The standard treatment should at least include platinum-containing and PD-1/PD-L1 inhibitor therapy (except when the patient refuses or the researcher determines that they are not suitable for immunotherapy). 2) Large cell neuroendocrine carcinoma of the lung (LCNEC), cohort A2/B2/C2/D2/E2 requires patients with recurrent or metastatic LCNEC of the lung who have progressed after =2 lines of standard treatment. Cohort F2/G2/H2 patients with recurrent or metastatic lung LCNEC who had progressed after <=1 line of standard treatment were required to have a time from the last platinum-based chemotherapy to disease progression exceeding 90 days. Standard treatment should at least include platinum-based treatment regimens. 3) Excluding SCLC and lung LCNEC, other neuroendocrine carcinomas: Cohort A3/B3/C3/D3/E3 requires patients with recurrent or metastatic other neuroendocrine carcinomas who have progressed after <=2 lines of standard treatment in the past; Cohort F3/G3/H3 requires patients with recurrent or metastatic other neuroendocrine carcinomas who have progressed after <=1 line of standard treatment in the past. For patients who have received platinum-based chemotherapy, the time from the last platinum-based chemotherapy to disease progression should exceed 90 days. Standard treatment should at least include platinum-based treatment regimens. 4) Other advanced or metastatic solid tumors: Previous failure of <=2 lines of standard treatment is required (only applicable to cohort A4/B4/C4/D4/E4). 4. The subjects are required to provide tumor tissue samples for DLL3 expression detection. The requirements for tumor tissue samples are as follows: neutral formalin-fixed and paraffin-embedded FFPE tissue blocks or at least 5 unstained tumor tissue sections. Both fresh and archived samples are
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria will not be allowed to enter this study: 1. Mixed neuroendocrine carcinoma and complex small cell lung cancer (excluding small cell lung cancer combined with large cell neuroendocrine carcinoma) 2. Accompanied by metastasis of tumors in the central nervous system (CNS) that have not received local treatment (radiotherapy or surgery) or are active. Subjects with a history of meningeal metastasis or those currently having meningeal metastasis. For subjects with CNS metastases, if the CNS tumor has received adequate local treatment (surgery or radiotherapy); No progression was found in imaging examinations from the end of local treatment to the screening period. The neurological symptoms of the subjects could stabilize for at least 2 weeks before the first administration, and no glucocorticoid treatment or prednisone (or equivalent hormone) of 470 ms (for females) or > 450 ms (for males); 6. Significant clinically significant bleeding symptoms occurred within 3 months before the first study of medication, and there was obvious hemoptysis within 1 month before the first study of medication, with each hemoptysis volume >=2.5ml. 7. In the first study, there was uncontrollable pleural effusion, peritoneal effusion or pericardial effusion within 2 weeks of medication, and repeated drainage was required; 8. Interstitial pneumonia occurred during previous treatment; A history of interstitial pneumonia such as idiopathic pulmonary fibrosis, organized pneumonia (such as oblusive bronchiolitis), drug-induced pneumonia, and radiation pneumonitis (excluding subjects with only radiation fibrosis in the radiation area and without steroid treatment); Non-infectious pulmonary inflammation that currently requires steroid treatme
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of dose-limiting toxicity (DLT), incidence and severity of adverse events (AE)/serious adverse events (SAE) (rated based on CTCAE v5.0); | — |
Secondary
| Measure | Time frame |
|---|---|
| The objective response rate evaluated by the researchers;Objective duration of tumor response;Disease control rate;progression free survival;overall survival; | — |
Countries
China
Contacts
Public ContactYu Jinming
Shandong Cancer Hospital
Outcome results
None listed