PD1-LAG3 Bispecific Antibody for Solid Tumors

Not currently recruiting at 53 trial locations

Overseen By Reference Study ID: NP41300 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hoffmann-La Roche

Must be taking: Anti-PD-1, Anti-PD-L1

Must not be taking: Immunosuppressants, Antibiotics

Disqualifiers: Pregnancy, CNS metastases, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called RO7247669, a PD1-LAG3 bispecific antibody, for individuals with advanced solid tumors. The trial aims to determine the safest dose and evaluate its effectiveness against cancer. It includes different groups, focusing on specific cancer types, such as melanoma or lung cancer. This trial may suit those who have tried other treatments without success and have a solid tumor diagnosis. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot be on regular immunosuppressive therapy or have had recent treatment with antibiotics or other investigational drugs.

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

Research shows that RO7247669, the treatment under study, has a good safety record. In earlier studies, participants handled the treatment well, experiencing few serious side effects. Most side effects were mild and manageable. Some studies also suggest that the treatment may help fight tumors, indicating its potential effectiveness. As this is an early-stage trial, the researchers focus on finding the optimal dose that balances safety and effectiveness. So far, the results appear promising for prospective participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for solid tumors, which often include chemotherapy and radiation, RO7247669 is a bispecific antibody that targets both PD-1 and LAG-3 pathways. This dual-targeting approach is exciting because it might enhance the immune system's ability to recognize and attack cancer cells more effectively than single-target therapies. Researchers are particularly interested in its potential to work in tumors that haven't responded well to existing immunotherapies, offering new hope for patients with limited options.

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

Research has shown that RO7247669, a special type of antibody, has produced promising results in early trials. This treatment targets two proteins, PD-1 and LAG-3, which help tumors evade the immune system. By blocking these proteins, RO7247669 may enhance the immune system's ability to find and attack cancer cells. Initial findings suggest that the treatment is generally safe and can shrink tumors. It has been well-tolerated by patients and has shown potential in reducing tumor size. However, more research is needed to fully understand its effectiveness in treating solid tumors. Participants in this trial will receive RO7247669 either in a single-agent dose escalation or in tumor-specific expansion cohorts to further evaluate its safety and effectiveness. ^{1 2 4 5 6}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced solid tumors, including melanoma and non-small cell lung cancer. Participants must have tried standard treatments without success or cannot tolerate them. They should be in good physical condition (ECOG 0-1) and agree to use birth control. Those with more than two prior treatments for metastatic disease or specific genetic mutations are excluded.

Inclusion Criteria

I have been treated with drugs targeting PD-1 or PD-L1.

My melanoma is at an advanced stage and cannot be surgically removed.

My cancer is advanced or has spread, and standard treatments are not suitable for me.

Exclusion Criteria

I have not received any live vaccines in the last 28 days.

I have another type of cancer that is currently active.

I have not received neo-adjuvant therapy targeting PD-1 or PD-L1.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive RO7247669 every 2 or 3 weeks to establish the maximum tolerated dose (MTD) and/or define the recommended phase 2 dose (RP2D)

Up to 24 months

Bi-weekly or tri-weekly visits

Tumor Specific Expansion

Participants with selected solid tumor indications receive RO7247669 at a dose derived from Part A to evaluate anti-tumor activity and confirm safety and tolerability

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• RO7247669

Trial Overview The study tests RO7247669, a new bispecific antibody targeting PD-1 and LAG-3 proteins on immune cells, which may help the body fight cancer. It's an early-phase trial to find the safest dose with potential anti-cancer effects in patients who've had previous treatments like PD-L1/PD-1 inhibitors.

How Is the Trial Designed?

Group I: Part B: Tumor Specific Expansion Cohorts Experimental Treatment 1 Intervention

Participants with selected solid tumor indications will receive RO7247669 at a dose derived from Part A until disease progression, unacceptable drug toxicity, or withdrawal of consent, for up to 24 months.

Group II: Part A: Single-Agent Dose Escalation Experimental Treatment 1 Intervention

Participants will receive RO7247669 every 2 weeks (Q2W) or every 3 weeks (Q3W) up to the maximum tolerated dose (MTD) until disease progression, unacceptable drug toxicity, or withdrawal of consent, for up to 24 months.

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

IBI323, a bispecific antibody targeting both PD-L1 and LAG-3, shows promising anti-tumor effects in preclinical models, demonstrating superior immune stimulation and anti-tumor activity compared to its parent antibodies.

In humanized mouse models, IBI323 not only effectively blocked key immune checkpoints but also enhanced the activation of tumor-specific T cells, suggesting it could be a valuable new approach for overcoming resistance to existing PD-1/PD-L1 therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1/LAG-3 bispecific antibody enhances tumor-specific immunity. Jiang, H., Ni, H., Zhang, P., et al.[2021]

In a phase 1 clinical trial involving 269 patients with advanced solid tumors or hematologic malignancies, tebotelimab, a bispecific PD-1×LAG-3 DART molecule, demonstrated safety with 68% of patients experiencing treatment-related adverse events, and a recommended phase 2 dose of 600 mg every 2 weeks was established.

Tebotelimab showed anti-tumor activity, with a 34% tumor decrease in patients treated with monotherapy and a 19% objective response rate in patients with HER2+ tumors when combined with the anti-HER2 antibody margetuximab, indicating potential effectiveness even in previously resistant cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The PD-1- and LAG-3-targeting bispecific molecule tebotelimab in solid tumors and hematologic cancers: a phase 1 trial. Luke, JJ., Patel, MR., Blumenschein, GR., et al.[2023]

The novel bispecific antibody YG-003D3 effectively targets both PD-1 and LAG-3 immune checkpoints, enhancing immune cell activation and demonstrating superior anti-tumor effects compared to single or combined therapies in vitro and in a mouse model.

In humanized mouse models, YG-003D3 not only showed strong anti-tumor activity but also significantly increased the presence of key immune cells (CD45+, CD3+, CD8+ T cells) in the tumor microenvironment, indicating its potential as a promising candidate for cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1/LAG-3 bispecific antibody potentiates T cell activation and increases antitumor efficacy. Shi, N., Zhou, Y., Liu, Y., et al.[2023]

FS118, a bispecific antibody targeting LAG-3 and PD-L1, was well tolerated in a phase 1 study with 43 patients who had advanced cancer resistant to anti-PD-(L)1 therapy, showing no serious adverse events or dose-limiting toxicities.

The study demonstrated a disease control rate of 46.5%, with a higher rate of 54.8% in patients receiving doses of 1 mg/kg or greater, indicating potential efficacy in this difficult-to-treat population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1 First-in-Human Study of FS118, a Tetravalent Bispecific Antibody Targeting LAG-3 and PD-L1 in Patients with Advanced Cancer and PD-L1 Resistance. Yap, TA., LoRusso, PM., Wong, DJ., et al.[2023]

The monoclonal antibody TSR-033 effectively targets LAG-3, enhancing T-cell activation and improving the immune response against tumors when used alongside PD-1 blockade in both in vitro and in vivo models.

In humanized mouse models of non-small cell lung carcinoma, TSR-033 significantly increased the antitumor efficacy of PD-1 therapy, leading to greater T-cell proliferation and durable immune memory, suggesting its potential as a powerful treatment option in cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TSR-033, a Novel Therapeutic Antibody Targeting LAG-3, Enhances T-Cell Function and the Activity of PD-1 Blockade In Vitro and In Vivo. Ghosh, S., Sharma, G., Travers, J., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04140500

NCT04140500 | Dose Escalation Study of a PD1-LAG3 ... Participants with selected solid tumor indications will receive RO7247669 at a dose derived from Part A until disease progression, unacceptable drug toxicity, ...

2. veri.larvol.com veri.larvol.com/news/ro7247669/drug

News - tobemstomig (RG6139) Conclusions RO7274669 has a favorable safety profile and has shown encouraging anti-tumor activity in the dose escalation phase. Expansion cohorts in CPI ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10935874/

The enhanced antitumor activity of bispecific antibody ... BsAbs offer a multifaceted approach to cancer immunotherapy by simultaneously targeting PD-L1 and other immune regulatory molecules.

4. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/dose-escalation-study-of-a-pd1-lag3-bispecific-antibody-65890.html

AN OPEN LABEL, MULTICENTER, DOSE ESCALATION ... A clinical trial to look at how safe and how well different doses of RO7247669 work in people with solid tumours that have grown or spread, and how the body ...

5. forpatients.roche.com forpatients.roche.com/content/patient-platform/global/en/trials/cancer/dose-escalation-study-of-a-pd1-lag3-bispecific-antibody-65890.pdf

A clinical trial to look at how safe and how well different doses ... This clinical trial aims to find out the highest, safest dose of RO7247669 that can be given, and to understand the side effects of RO7247669 at different doses ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04785820

NCT04785820 | A Study of Lomvastomig (RO7121661 ... This is a Phase II, randomized, blinded, active-controlled, global, multicenter study designed to evaluate the safety and efficacy of lomvastomig and ...