LB101 for Solid Tumors

No longer recruiting at 7 trial locations

Overseen By Centessa Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Centessa Pharmaceuticals (UK) Limited

Must not be taking: Immunosuppressants, Glucocorticoids, Live vaccines, others

Disqualifiers: Autoimmune diseases, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of a new treatment called LB101 (PD-L1xCD47 LockBody) for individuals with advanced solid tumors. The main goal is to assess how well the treatment is tolerated and its performance against these challenging cancers. It targets individuals with advanced cancer who have not found success with other treatments. The trial is open to those with specific cancer types, such as certain lung, head and neck, cervical, and ovarian cancers, particularly if previous treatments have failed. Participants should have measurable tumors and be willing to undergo specific tests and biopsies. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot participate if you have received immunosuppressive drugs within 7 days before starting LB101 or if you have ongoing side effects from previous therapies. It's best to discuss your current medications with the trial team.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have taken immunosuppressive drugs within 7 days before starting the trial or if you have ongoing side effects from previous treatments.

Is there any evidence suggesting that LB101 is likely to be safe for humans?

Research shows that LB101 is a new treatment under testing for advanced solid tumors. Currently, limited information exists on its safety in humans. The treatment is in early testing stages, so researchers are determining the best dose and checking for side effects.

LB101 is a bispecific monoclonal antibody that targets specific proteins on cancer cells to help the immune system fight cancer. Since the treatment is still in Phase 1/2 trials, it has shown enough promise in lab and animal studies to warrant testing in humans. This suggests potential safety, but detailed safety information for humans remains unavailable.

In these early stages, researchers closely monitor participants to identify any side effects. This helps them understand how well the treatment is tolerated in humans. Participants in the trial can expect regular check-ups to ensure their safety while receiving LB101. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about LB101 because it represents a novel approach to treating solid tumors. Unlike many current cancer treatments that often target rapidly dividing cells indiscriminately, LB101 is designed to specifically target and bind to cancer cells, potentially minimizing damage to healthy cells. This targeted mechanism could lead to more effective treatments with fewer side effects, making it a promising option in the fight against solid tumors.

What evidence suggests that LB101 might be an effective treatment for solid tumors?

Research has shown that LB101, the investigational treatment in this trial, may help treat advanced solid tumors. In early results, LB101 improved the response duration and effectiveness in 14 out of 16 tumors. It targets the PD-L1 protein, enhancing the immune system's ability to fight cancer. Additionally, studies in animals, such as monkeys, found that high doses of LB101 could be administered without causing blood-related side effects. These findings suggest LB101 might enhance the body's defense system against solid tumors. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

Adults (18+) with advanced solid tumors, including specific types of lung, head and neck, cervical, ovarian cancers. Must have tried checkpoint inhibitors previously or have no standard treatment options left. Participants need to be in relatively good health with a life expectancy of at least 12 weeks and weigh over 40 kg. They must agree to use two effective contraception methods if applicable and provide tissue samples.

Inclusion Criteria

Participants with life expectancy >= 12 weeks

My blood counts are within a healthy range.

I have a stored sample of my tumor tissue.

Exclusion Criteria

I have not received immunotherapy for my cancer.

My advanced disease worsened within 6 months after finishing my initial cancer treatment.

I am currently on IV medication for an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Part 1a)

Participants receive LB101 once every 2 weeks in a 28-day cycle to determine safe dose levels

28 days

2 visits (in-person)

Dose Optimization (Part 1b)

Participants receive optimized dose levels and/or schedules deemed safe from Part 1a

Varies based on dose schedule

Dose Expansion (Part 2)

Further evaluation of safety, efficacy, tolerability, pharmacokinetics, and immune response of LB101

Varies based on results from Part 1

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LB101

Trial Overview The trial is testing LB101 as a solo treatment for various advanced solid tumors to see how safe it is and if it works. It involves people who've already had certain treatments like immune checkpoint inhibitors or those without other treatment choices.

How Is the Trial Designed?

Group I: LB101 Experimental Treatment 1 Intervention

Part 1 Part 1a participants will receive LB101 once every 2 weeks (Q2W) (28-day cycle), with a preliminary plan for 6 sequential dose levels. Part 1b will be a dose optimization and will include \>1 dose levels and/or dose schedules that have been deemed safe and tolerable in Part 1a. Part 2 Dose regimen(s) for participants in Part 2 will be based on the results of Part 1.

LB101 is already approved in United States for the following indications:

Approved in United States as LB101 for:

• None approved; currently in Phase 1/2a clinical trial for advanced solid tumors

Who Is Running the Clinical Trial?

Centessa Pharmaceuticals (UK) Limited

Lead Sponsor

Trials

2

Recruited

100+

LockBody Therapeutics Ltd

Industry Sponsor

Trials

1

Recruited

30+

Published Research Related to This Trial

The novel bispecific T cell engager (BiTE) PD-L1×CD3 nanobody effectively activates T cells to produce important immune signals (TNF-α and IFN-γ) in a dose-dependent manner, with an IC50 value of 4.208 μg/mL.

BiTE PD-L1×CD3 Nb demonstrated significant cytotoxic activity against melanoma cells, particularly those with high PD-L1 expression, indicating its potential as a targeted therapy for advanced melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A PD-L1xCD3 bispecific nanobody as a novel T-cell engager in treating PD-L1 overexpression melanoma. Li, B., Wang, S., Shan, B., et al.[2023]

A new noninvasive imaging technique using radiolabeled antibodies can effectively determine PD-L1 expression in tumors, which is crucial for selecting patients who are likely to benefit from anti-PD-1/PD-L1 therapies.

The study demonstrated that the radiolabeled antibody (111)In-PD-L1.3.1 specifically accumulates in tumors with high PD-L1 expression, allowing for better patient stratification and monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive Imaging of Tumor PD-L1 Expression Using Radiolabeled Anti-PD-L1 Antibodies. Heskamp, S., Hobo, W., Molkenboer-Kuenen, JD., et al.[2021]

The newly developed PET tracers [18F]AlF-NOTA-ZPD-L1_4 and [68Ga]NOTA-ZPD-L1_4 showed significantly higher accumulation in PD-L1 positive tumors compared to PD-L1 negative tumors, indicating improved targeting for monitoring PD-L1 expression during immunotherapy.

Both tracers demonstrated favorable biodistribution in rhesus monkeys, with fast kidney clearance and low liver background, suggesting they are suitable for same-day clinical imaging of PD-L1, although high kidney accumulation may limit the radioactive doses used in repeated studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo Evaluation and Dosimetry Estimate for a High Affinity Affibody PET Tracer Targeting PD-L1. Rubins, DJ., Meng, X., McQuade, P., et al.[2021]

The study successfully developed a Nanobody-based probe for imaging human PD-L1 expression using positron emission tomography, achieving over 95% radiochemical purity with two different radiolabeling strategies.

Both site-specific and random conjugation methods for labeling the Nanobody showed effective tumor targeting in vivo, indicating that random lysine-conjugation is a viable option for clinical applications despite potential concerns about affinity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-human PD-L1 Nanobody for Immuno-PET Imaging: Validation of a Conjugation Strategy for Clinical Translation. Bridoux, J., Broos, K., Lecocq, Q., et al.[2021]

The PD-1 pathway plays a crucial role in suppressing T-cell activation, which is important for maintaining immune tolerance, but its high expression in tumors contributes to a suppressive environment that promotes cancer growth.

Blocking the PD-1 axis using PD-L2 fusion proteins or monoclonal antibodies has been clinically tested across various tumor types, showing promise in enhancing antitumor immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Cancer Immunotherapy with PD-1/PD-L1 Blockade. Zheng, P., Zhou, Z.[2022]

In a case report involving three patients with renal cell carcinoma and melanoma, all experienced disease progression after receiving a second PD-1 inhibitor (nivolumab) following initial treatment with a PD-1/PD-L1 inhibitor, indicating limited efficacy of sequential PD-1 therapies.

The authors recommend that clinicians avoid using multiple PD-1/PD-L1 inhibitors sequentially outside of clinical trials until more data is available, highlighting the need for further research to understand the mechanisms of resistance and to validate the safety and efficacy of these treatments in later lines of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to single agent PD-1 inhibitor after progression on previous PD-1/PD-L1 inhibitors: a case series. Martini, DJ., Lalani, AA., Bossé, D., et al.[2018]

A novel PD-L1-binding affibody (M1) was developed using mRNA display, demonstrating low nanomolar affinity for both human and mouse PD-L1, which is crucial for potential diagnostic applications.

The M1 affibody effectively inhibited PD-L1:PD-1 signaling in a cell-based assay and showed significant tumor uptake in vivo, indicating its potential as a molecular imaging probe in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Directed Evolution of PD-L1-Targeted Affibodies by mRNA Display. Grindel, BJ., Engel, BJ., Ong, JN., et al.[2023]

In a study of 144 breast cancer patients, PD-L1 expression was found more frequently in triple negative breast cancer (TNBC) patients, suggesting that these patients may benefit from PD-L1 inhibition therapy due to their resistance to standard chemotherapy.

The study found no significant difference in soluble PD-L1 serum levels between breast cancer patients and healthy women, indicating that low serum levels of sPD-L1 are unlikely to interfere with PD-L1 inhibition therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 expression in tumor lesions and soluble PD-L1 serum levels in patients with breast cancer: TNBC versus TPBC. Yazdanpanah, P., Alavianmehr, A., Ghaderi, A., et al.[2021]

The PD-L1/PD-1 axis is a crucial immune checkpoint mechanism that cancer cells exploit to evade immune detection, making it a key target for cancer immunotherapy with FDA-approved anti-PD-L1 antibodies like atezolizumab, durvalumab, and avelumab.

While anti-PD-L1 antibodies show promise in clinical trials, their effectiveness can be limited by factors such as low T cell infiltration in tumors; thus, using these antibodies as carriers for toxic payloads (immunoconjugates) may enhance their therapeutic potential against PD-L1 expressing cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD-L1 immunoconjugates for cancer therapy: Are available antibodies good carriers for toxic payload delivering? Zanello, A., Bortolotti, M., Maiello, S., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05821777

NCT05821777 | A Study to Evaluate Safety, Tolerability ... The purpose of this study is to assess safety, tolerability, and preliminary activity of LB101 monotherapy in participants with advanced solid tumors. Detailed ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.2562

LB101, a conditionally tetravalent PD-L1xCD47 bispecific ... Monotherapy LB101 exhibited greatly improved efficacy and durability of response (14/16 tumors ... solid tumors: Interim results. Sophia Frentzas ...

3. investors.centessa.com investors.centessa.com/news-releases/news-release-details/centessa-pharmaceuticals-announces-non-human-primate

Release Details These new non-clinical data demonstrate systemic delivery of high doses of LB101 without hematological toxicity in non-human primates, resulting ...

4. withpower.com withpower.com/trial/phase-2-neoplasms-2-2023-a7c4f

LB101 for Solid Tumors · Info for Participants Research shows that blocking the PD-L1 protein, which is targeted by LB101, can help the immune system fight cancer cells more effectively. Similar treatments ...

5. ctv.veeva.com ctv.veeva.com/study/a-study-to-evaluate-safety-tolerability-and-preliminary-activity-of-lb101-in-participants-with-adva

A Study to Evaluate Safety, Tolerability and Preliminary ... The purpose of this study is to assess safety, tolerability, and preliminary activity of LB101 monotherapy in participants with advanced solid tumors.

6. investors.centessa.com investors.centessa.com/node/8161/ixbrl-viewer

0001847903-23-000032 | 8-K | iXBRL Viewer LB101 is a conditionally tetravalent PD-L1xCD47 LockBody bispecific monoclonal antibody, being developed for solid tumors. BOSTON & LONDON, January 26, 2023 ...