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This is a Phase I study designed to evaluate if experimental anti-PD-1 and anti-TIM-3 bispecific antibody, LB1410, is safe, tolerable and efficacious in participants with advanced solid tumors or lymphoma.
This first time in patients, open-label, multi-centre study will have LB1410 administered intravenously (IV) to participants with advanced solid tumors or lymphoma. This study will have 2 parts: Part A which will have dose escalation cohorts and Part B which will have the dose expansion cohorts.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Escalation | Experimental | Up to 9 dose cohorts will be sequentially enrolled in the dose escalation part using an accelerated titration combined with the standard 3+3 dose escalation algorithm approach. |
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| Safety Expansion | Experimental | 2-3 doses were initially selected for safety expansion, with patients with advanced solid tumors as the main research population. Each dose cohort is expected to enroll 9-12 patients. |
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| Exploratory Expansion | Experimental | The Cohort Exploratory Expansion will enroll subjects by cohort at the RP2D dose, and a total of 4 cohorts (cohorts A, B, C, D) are expected. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LB1410 | Drug | anti-PD-1 and anti-TIM-3 bispecific antibody |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence and severity of treatment-emergent adverse events (TEAEs) | According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. | up to 30 days following last dose. |
| Incidence and severity of serious adverse events (SAEs) | According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. | up to 90 days following last dose. |
| AEs of special interest (immune-related AEs) | Incidence and severity of immune-related AEs. | up to 90 days following last dose. |
| Incidence of DLTs | The DLT for this study is defined according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 and will be evaluated in the dose escalation part, the first 28 days (Cycle 1) of treatment. | in the first 28 days (Cycle 1). |
| Measure | Description | Time Frame |
|---|---|---|
| Serum PK parameters | AUC0-t and so on. | Up to finished treatment (each cycle is 28 days). |
| Overall response rate (ORR) | Evaluation Criteria in Solid Tumors (RECIST) v 1.1 and Immunotherapeutics Response Evaluation Criteria in Solid Tumors (iRECIST) and Response Evaluation Criteria in Lymphoma (2017) (RECIL 2017). |
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Inclusion Criteria:
Must be ≥ 18 years of age
For dose escalation and safety expansion phases only, patient must have histologically or cytologically confirmed advanced and/or metastatic solid tumor malignancies or lymphoma for which standard treatment fails, or no standard treatment is available, or standard treatment is not applicable at this stage
Cohort specific inclusion criteria:
Cohort A: NSCLC patients with histologically confirmed advanced or metastatic NSCLC who have previously failed anti-PD1/anti-PD-L1 antibody and platinum-based chemotherapy, and have not discontinued treatment due to AEs
Cohort B: NSCLC patients with histologically confirmed advanced or metastatic NSCLC who have failed previous platinum-containing doublet chemotherapy but have not received PD1/PD-L1 antibody therapyï¼›PD-L1 positive
Cohort C: CRC patients with advanced colorectal cancer who have received no more than 2 lines of systemic therapy in the past; TIM-3≥10%
Cohort D: Other advanced solid tumors patients who have received no more than two lines of systemic therapy, including but not limited to small cell lung cancer, endometrial cancer, anal cancer, ovarian cancer, head and neck squamous cell carcinoma, gastric adenocarcinoma or gastroesophageal junction cancer patients
During the screening period, tumor tissue wax blocks or white slices of pathological biopsy sections shall be provided, or tumor tissue biopsy materials shall be allowed to be collected for PD-L1 and TIM-3 detection
Eastern Cooperative Oncology Group Performance Status 0-1
Patients with a life expectancy≥12 weeks
Must have at least one measurable lesion for assessment by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or standard criteria for lymphoma (RECIL 2017)
Adequate hematological and organ function measured within 7 days prior to first dose
Non-pregnant women and willingness of female participants to avoid pregnancy or male participants willing to avoid fathering children through highly effective methods of contraception
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yan Luan | Contact | +86-21-54152522 | luanyn2@lnlbio.com |
| Name | Affiliation | Role |
|---|---|---|
| Caicun Zhou | Shanghai Pulmonary Hospital, Shanghai, China | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shanghai Pulmonary Hospital | Recruiting | Shanghai | Shanghai Municipality | China |
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| ID | Term |
|---|---|
| D008223 | Lymphoma |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
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| through study completion, an average of 8 months. |
| Disease control rate (DCR) | Evaluation Criteria in Solid Tumors (RECIST) v 1.1 and Immunotherapeutics Response Evaluation Criteria in Solid Tumors (iRECIST) and Response Evaluation Criteria in Lymphoma (2017) (RECIL 2017). | through study completion, an average of 8 months. |
| Progression-free survival (PFS) | Evaluation Criteria in Solid Tumors (RECIST) v 1.1 and Immunotherapeutics Response Evaluation Criteria in Solid Tumors (iRECIST) and Response Evaluation Criteria in Lymphoma (2017) (RECIL 2017). | through study completion, an average of 8 months. |
| Duration of response (DOR) | Evaluation Criteria in Solid Tumors (RECIST) v 1.1 and Immunotherapeutics Response Evaluation Criteria in Solid Tumors (iRECIST) and Response Evaluation Criteria in Lymphoma (2017) (RECIL 2017). | through study completion, an average of 8 months. |
| Immunogenicity | Incidence of anti-drug anti-body (ADA) including the number and percentage of participants who develop detectable ADA. | up to 90 days following last dose. |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |