Evaluating LB1410 for advanced solid tumors and lymphoma

A Phase 1, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of LB1410, A Recombinant Anti-PD-1 and Anti-TIM-3 Humanized Bispecific Antibody for Injection in Patients With Advanced Solid Tumors or Lymphoma（Keyplus-001）

This study is testing a new treatment called LB1410 to see if it is safe and effective for people with advanced solid tumors or lymphoma.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: L & L Bio Co., Ltd., Ningbo, China (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, prednisone
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT05357651 on ClinicalTrials.gov

What this trial studies

This Phase I study aims to assess the safety, tolerability, and efficacy of LB1410, an experimental bispecific antibody targeting PD-1 and TIM-3, in patients with advanced solid tumors or lymphoma. The study is open-label and multi-centre, involving intravenous administration of LB1410. It consists of two parts: Part A focuses on dose escalation cohorts, while Part B involves dose expansion cohorts to further evaluate the treatment's effects.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with advanced solid tumors or lymphoma that have not responded to standard therapies.

Not a fit: Patients with early-stage tumors or those who have not yet received standard treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors or lymphoma who have exhausted standard treatment options.

How similar studies have performed: Other studies involving bispecific antibodies targeting immune checkpoints have shown promise, indicating potential for success in this novel approach.

Eligibility criteria

Inclusion Criteria:

1. Must be ≥ 18 years of age
2. 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
3. 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 therapy；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
4. 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
5. Eastern Cooperative Oncology Group Performance Status 0-1
6. Patients with a life expectancy≥12 weeks
7. 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)
8. Adequate hematological and organ function measured within 7 days prior to first dose
9. 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:

1. Pregnancy, lactation, or breastfeeding
2. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments
3. Treatment with anti-cancer therapy or investigational therapy within 28 days prior to the first dose of LB1410
4. Patients who have used PD1 monoclonal antibody and TIM3 monoclonal antibody (both simultaneously or sequentially) in the past, and patients who have used one of them alone can be included
5. Immunosuppressive corticosteroid doses (\>10 mg prednisone daily or equivalent) within 2 weeks prior to the first dose of LB1410
6. Active infection , including known infection with human immunodeficiency virus (HIV), or active infection with hepatitis B HBV (HBV DNA\> 1000 copy/mL or 200 IU/mL) or hepatitis C virus (HCV)
7. Previous malignant disease (other than the target malignancy to be investigated in this trial) within the last 3 years. Subjects with history of cervical carcinoma in situ, superficial, or non-invasive bladder cancer, or basal cell, or squamous cell cancer in situ or other in situ cancers previously treated with curative intent may be included at the judgment of Investigator
8. History of documented allergic reactions or acute hypersensitivity reactions attributed to treatment with antibody therapies in general, or to any of the components of LB1410
9. Symptomatic or uncontrolled brain metastases, spinal cord compression, or leptomeningeal disease requiring concurrent treatment, including but not limited to surgery, radiation, and/or corticosteroids (participants receiving anticonvulsants are eligible)
10. Participant has not recovered (i.e., to \<= Grade 1 or Baseline) from radiation- and chemotherapy-induced AEs (except alopecia, peripheral neuropathy, and ototoxicity, which are excluded if ≥ CTCAE grade 3)
11. History of organ transplantation
12. Inadequate recovery from any prior surgical procedure or having undergone any major surgical procedure within 4 weeks prior to the study drug treatment
13. Impaired cardiac function or clinically significant cardiac disease, including any of the following
14. Interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention)
15. Type 2 diabetes mellitus or type 2 diabetes patients with poor glycemic control.
16. Underlying medical conditions that, in the Investigator's opinion, will make the administration of the study drug hazardous or obscure the interpretation of toxicity determination or adverse events
17. Patients with a history of active tuberculosis infection within 1 year before enrollment
18. Those with a clear history of neurological or mental disorders, such as epilepsy and dementia, and poor compliance
19. Patients with a history of chronic gastrointestinal inflammation, any active inflammation during screening, or grade 3 or above gastrointestinal reaction after previous immunotherapy

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Pulmonary Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Caicun Zhou — Shanghai Pulmonary Hospital, Shanghai, China
• Study coordinator: Yan Luan

Conditions Solid Tumor; Lymphoma