PD1-LAG3 Bispecific Antibody for Solid Tumors

Recruiting at 43 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

170 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug RO7247669 for solid tumors?

Research on similar bispecific antibodies targeting PD-1 and LAG-3 shows that they can enhance the body's immune response against tumors by activating immune cells more effectively than using single-target drugs. These studies suggest that targeting both PD-1 and LAG-3 can improve antitumor activity, making it a promising approach for cancer treatment. ^{1 2 3 4 5}

Is the PD1-LAG3 bispecific antibody safe for humans?

In a phase 1 trial of a similar bispecific antibody called tebotelimab, 68% of patients experienced treatment-related side effects, with 22% being severe. No maximum tolerated dose was found, and the recommended dose for further study was 600 mg every two weeks. ^{1 2 4 5 6}

What makes the drug RO7247669 unique for treating solid tumors?

RO7247669 is a bispecific antibody that targets both PD-1 and LAG-3, which are proteins that can suppress the immune system's ability to fight cancer. This dual targeting approach is designed to enhance the immune response against tumors more effectively than treatments that target only one of these proteins. ^{1 2 3 4 5}

What is the purpose of this trial?

This is a first-in-human, open-label, multicenter, Phase I multiple-ascending dose (MAD) study of RO7247669, an anti PD-1 (programmed death-1) and LAG-3 (Lymphocyte-activation gene 3) bispecific antibody, for participants with advanced and/or metastatic solid tumors. This study aims to establish the maximum tolerated dose (MTD) and/or define the recommended phase 2 dose (RP2D) based on the safety, tolerability, pharmacokinetic (PK) and/or pharmacodynamic (PD) profile of RO7247669, and to evaluate preliminary anti-tumor activity in participants with solid tumors. An expansion part of the study is planned to enroll tumor-specific cohorts to evaluate anti-tumor activity of the MTD and/or RP2D of RO7247669 and to confirm safety and tolerability in participants with selected tumor types.

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

PD-L1/LAG-3 bispecific antibody enhances tumor-specific immunity. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

PD-1/LAG-3 bispecific antibody potentiates T cell activation and increases antitumor efficacy. [2023]

3. United States 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. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Clinical landscape of LAG-3-targeted therapy. [2022]

5. United States 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. [2023]

6. United States 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. [2023]