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

• Status: Recruiting
• Trial end date: 2027-01-05
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centessa Pharmaceuticals (UK) Limited
• Collaborator: LockBody Therapeutics Ltd

Criteria

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, with no actionable genomic alteration for which approved therapy exists, after having received immune checkpoint inhibitor at any stage of their prior therapy

• 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)

• Ovarian cancer which is platinum resistant, and which is not platinum refractory

• Participants have measurable disease according to RECIST v1.1

• Available archived tumor tissue sample (Part 1a)

• Willingness to provide consent for biopsy sample (Part 1b and 2)

• 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

• Participants with known negative PD-L1 status

• Participants with NSCLC, head and neck squamous cell carcinoma, cervical cancer, or cutaneous squamous cell carcinoma that have not received checkpoint inhibitor for advanced/metastatic disease

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

• Participants with platinum refractory ovarian cancer

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

• Participants have received prior anticancer therapy within certain specified time frames prior to the start of LB101 including anticancer therapy (chemotherapy, endocrine therapy, targeted therapy, or tumor embolization), immunotherapy/monoclonal antibodies/antibody-drug conjugates, nitrosoureas, radioactive isotopes, radiotherapy, major surgery, chronic corticosteroid treatment

• 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

• Participants not eligible to participate in the study at the discretion of the Investigator