A Study to Evaluate Safety, Tolerability and Preliminary Activity of LB101 in Participants With Advanced Solid Tumors

A Phase 1/2a, First in Human, Open-Label, Multicenter, Dose Escalation Study With Expansion Cohorts to Evaluate the Safety, Tolerability, and Preliminary Activity of LB101 in Subjects With Advanced Solid Tumors

The purpose of this study is to assess safety, tolerability, and preliminary activity of LB101 monotherapy in participants with advanced solid tumors.

This study consists of 2 parts: First in Human (FIH) dose escalation and dose optimization (Part 1a and Part 1b, respectively) and dose expansion (Part 2). Part 1 will evaluate LB101 monotherapy in participants with selected, advanced solid tumors and determine the Recommended Dose(s) for Expansion (RDE(s)) for Part 2. The design of Part 2 depends on the results of Part 1 and will further evaluate the safety, efficacy, tolerability, pharmacokinetics, and immune response of LB101.

Inclusion Criteria:

• Male or female participants >= 18 years old
• Signed informed consent form (ICF)
• For Part 1: Participants who i). have a histologically confirmed solid tumor that is listed below and is advanced, unresectable, and/or metastatic and ii). have no standard therapy, are not candidates for available standard therapy, or have failed systemic therapy due to lack of response, progression, or intolerance:
• Non-small cell lung cancer (NSCLC), which is known to be PD L1 positive (combined positive score [CPS] ≥ 1 or tumor proportion score [TPS] ≥ 1%) after having received pembrolizumab or other analog immune checkpoint inhibitor at any stage of their prior therapy I. Subjects with PD-L1 positive NSCLC with known genomic alterations for which targeted therapy is approved are not required to have been treated with pembrolizumab, etc. but must have received such approved targeted therapy. Genomic alternations include, but are not limited to, epidermal growth factor receptor [EGFR] and anaplastic lymphoma kinase [ALK]
• Head and neck squamous cell carcinoma or cervical cancer, which is known to be PD-L1-positive, after having received immune checkpoint inhibitor at any stage of their prior therapy
• Cutaneous squamous cell cancer after having received immune checkpoint inhibitor at any stage of their prior therapy
• Colorectal cancer with low level microsatellite instability (MSI-low) and/or microsatellite stable(MSS)
• Ovarian cancer which is platinum resistant or platinum refractory, with platinum free interval of less than 6 months, and without rapidly progressing disease in the investigator's judgment
• Gastric cancer which is known to be PD-L1 positive after having received pembrolizumab or other analog immune checkpoint inhibitor at any stage of their prior therapy
• Participants have measurable disease according to RECIST v1.1
• Available archived tumor tissue sample (Part 1a)
• In Part 1a backfill cohort(s), Part 1b, and Part 2, subjects must agree to undergo baseline tumor biopsy
• Participants have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Participants have adequate hematological function
• Participants have adequate hepatic and renal function
• Participants have a baseline QT interval as corrected by Fridericia's formula <= 480 milliseconds
• Participants with life expectancy >= 12 weeks
• Participants have a body weight >= 40 kilograms
• For female participants of childbearing potential:
• Negative urine or serum pregnancy test
• Willing to use 2 highly effective methods of contraception
• For male participants who can father a child:
• Willing to use 2 highly effective methods of contraception

Exclusion Criteria:

• Participants with unknown PD-L1 status for the following tumor types: NSCLC, head and neck squamous cell carcinoma, or cervical cancer

  a.In Part 1a backfill cohort(s), any subject with unknown PD-L1 status

• Participants with known negative PD-L1 status

• Participants with NSCLC, head and neck squamous cell carcinoma, cervical cancer, cutaneous squamous cell cancer, or gastric cancer that have NOT received checkpoint inhibitor for advanced/metastatic disease, unless such therapy is not approved for treating a subject's specific condition

• Participants who receive adjuvant systemic therapy and progressed with advanced disease within 6 months of completing treatment

• Participants who have had previous exposure to CD47 or SIRPα targeting anticancer therapy

• Participants participating in another interventional clinical study

• Participants who have ongoing side effects to any prior therapy or procedure, which have not recovered to NCI CTCAE Grade <= 1

• Participants who have received immunosuppressive drugs within 7 days prior to the start of LB101 or systemic glucocorticoids equivalent

• Participants who have received a live attenuated vaccine within 4 weeks prior to the start of LB101. For any subject receiving an approved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, the investigator will be advised to follow the vaccine label and/or local guidance

• Participants with primary brain tumors and evidence of new or progressing cerebrospinal or leptomeningeal metastases

• Participants who have a history of Grade ≥ 3 allergic reactions to monoclonal antibody therapy as well as known or suspected allergy or intolerance to any components of LB101

• Participants with active or suspected systemic inflammatory autoimmune diseases or with a history of documented autoimmune disease over the past 2 years

• Participants who have ongoing or active infection requiring IV anti-infective medications

• Participants with a known history of:

• Seropositivity for human immunodeficiency virus (HIV)

• Positive serology for hepatitis B, known history/positive serology for hepatitis C virus (HCV)

• Allogenic organ transplantation and/or hematopoietic stem cell transplantation

• Participants who have had a history of life-threatening treatment-related AEs with prior immunotherapy or who have not recovered from prior cancer therapy-induced AEs

• Participants with clinically significant ascites

• Participants with moderate bilateral pleural effusion or massive bilateral pleural effusion or respiratory dysfunction requiring drainage

• Participants with uncontrolled cardiovascular disease

• Participants with any other acute or chronic diseases, psychiatric disorders, or abnormal laboratory test values that, at the discretion of the investigators are deemed ineligible to participate

• Participants with a history of other advanced solid tumor malignancies except:

• Cured malignant tumors for > 2 years prior to enrollment and no known active disease

• Tumors with negligible risk of metastases or death

• Pregnant or lactating female participants