RO7247669 for Melanoma

Not currently recruiting at 38 trial locations

Overseen By Reference Study ID Number: BP43963 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hoffmann-La Roche

Must not be taking: Immunomodulatory agents

Disqualifiers: Ocular melanoma, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called RO7247669, an anti-PD-1/anti-LAG-3 bispecific antibody, for individuals with advanced melanoma. This type of skin cancer cannot be surgically removed or has spread to other parts of the body. The study aims to determine the safety and effectiveness of this treatment by testing two different doses. Participants will receive either a high or low dose every three weeks to identify the most effective option. Suitable candidates have melanoma that cannot be surgically removed or has spread, and they know their tumor's BRAF mutation status. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had prior systemic anticancer therapy for unresectable or metastatic melanoma or certain immunomodulatory agents.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have had prior systemic anticancer therapy for melanoma, you may not be eligible to participate.

Is there any evidence suggesting that RO7247669 is likely to be safe for humans?

Research shows that RO7247669 could be a promising treatment for melanoma. Earlier studies found this treatment to be generally safe. Most patients tolerated it well, with only a few experiencing serious side effects. For example, one study found that only 2.5% of patients had severe side effects, a lower rate compared to some other cancer treatments. As the drug is still under investigation, researchers closely monitor its safety. Prospective participants should know that while some side effects might occur, past studies have shown the treatment to be well-received. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for melanoma?

RO7247669 is unique because it offers a new approach to treating melanoma by potentially targeting specific pathways that other treatments may not address. Most treatments for melanoma, like immunotherapies and targeted therapies, work by enhancing the immune system or targeting specific genetic mutations. However, RO7247669 is designed to be administered in varying doses every three weeks, which could optimize its effectiveness and minimize side effects. Researchers are excited about the potential of RO7247669 to provide a more tailored treatment option that could improve outcomes for patients with melanoma.

What evidence suggests that RO7247669 might be an effective treatment for melanoma?

Research shows that RO7247669, a treatment targeting both PD-1 and LAG-3 proteins, holds promise in fighting melanoma, a type of skin cancer. This trial will evaluate RO7247669 at different dosages, with participants receiving either a high or low dose every three weeks. Studies have found that this treatment can slow cancer progression longer than PD-1 inhibitors alone. This combination strongly affects tumors and only slightly increases side effects compared to using one treatment alone. Early results suggest that this dual approach might more effectively stop cancer growth. These findings encourage those considering joining a clinical trial for this treatment. ^{1 3 6 7 8}

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 unresectable or metastatic melanoma, who haven't had certain previous treatments. They must have measurable disease, be in good physical condition (ECOG 0-1), and have their major organs functioning well. Participants can't join if they've had anti-LAG3 therapy, ocular melanoma, recent serious health events like heart attacks or strokes, are pregnant/breastfeeding, or have active infections.

Inclusion Criteria

I know my cancer's BRAF V600 mutation status.

Your disease can be measured using specific guidelines for imaging.

My melanoma cannot be surgically removed and is classified as Stage III or IV.

Exclusion Criteria

I haven't had a major heart or stroke issue in the last 6 months.

I have previously been treated with anti-LAG3 therapy.

I have had treatment for melanoma that couldn't be removed by surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive RO7247669 every three weeks until loss of clinical benefit, unacceptable toxicity, or a maximum of 24 months

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• RO7247669

Trial Overview The study tests two doses of a new medication called RO7247669 to see how effective and safe it is for treating melanoma that cannot be removed by surgery or has spread. Researchers will also look at how the body processes the drug and its effects on the disease.

How Is the Trial Designed?

Group I: Low dose every three weeks (Q3W) Experimental Treatment 1 Intervention

Participants will receive RO7247669 Q3W until loss of clinical benefit, unacceptable toxicity, or a maximum of 24 months.

Group II: High dose Q3W Experimental Treatment 1 Intervention

Participants will receive RO7247669 Q3W until loss of clinical benefit, unacceptable toxicity, or a maximum of 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

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 both LAG-3 and PD-L1, shows promise in overcoming resistance to PD-L1 therapies by enhancing T-cell activity and reducing immune suppression, demonstrating better efficacy than using single antibodies.

In mouse models, FS118 significantly suppressed tumor growth and revealed a unique mechanism where treatment led to decreased LAG-3 expression on T cells, suggesting a novel way to reinvigorate exhausted immune cells in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FS118, a Bispecific Antibody Targeting LAG-3 and PD-L1, Enhances T-Cell Activation Resulting in Potent Antitumor Activity. Kraman, M., Faroudi, M., Allen, NL., et al.[2022]

In a study of 100 melanoma patients treated with adjuvant anti-PD-1 antibodies (nivolumab and pembrolizumab), 39% experienced disease recurrence after a median follow-up of 11.5 months, with 12-month recurrence-free survival at 64.8%.

The treatment was associated with a manageable safety profile, as 16 patients had severe adverse events and 22 discontinued treatment due to side effects, while also proving to be cost-effective at €13,330 per quality-adjusted life year compared to observation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant anti-PD-1 antibody treatment in stage III/IV melanoma: real-world experience and health economic considerations. Koelblinger, P., Hoellwerth, M., Dernoscheg, MT., et al.[2021]

Nivolumab and pembrolizumab, two anti-PD-1 antibodies, have demonstrated significant antitumor activity and acceptable safety profiles in patients with metastatic melanoma during early clinical trials.

Ongoing Phase III studies are further evaluating the efficacy and safety of anti-PD-1 therapies, including promising results from combinations with other treatments like anti-CTLA-4 antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD1 and anti-PD-L1 in the treatment of metastatic melanoma. Simeone, E., Grimaldi, AM., Ascierto, PA.[2023]

The study introduces new bi-specific and tri-specific antibodies (GB265, GB266, and GB266T) that target PD-L1, TIGIT, and LAG-3, showing enhanced T cell expansion and tumor cell killing in laboratory tests compared to existing treatments.

In animal models, the new antibodies demonstrated superior tumor suppression, suggesting they could effectively overcome resistance seen with current cancer immunotherapies that target single immune checkpoints.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fc-competent multispecific PDL-1/TIGIT/LAG-3 antibodies potentiate superior anti-tumor T cell response. Yang, R., Huang, S., Huang, C., et al.[2023]

Blocking the PD-1 pathway with specific drugs has shown clinical effectiveness in treating advanced cancers like melanoma and lung cancer, by enhancing the body's anti-tumor immune response.

These PD-1/PD-L1 blocking drugs have a manageable safety profile, making them suitable for outpatient treatment and potential use in combination therapies, with ongoing research focused on identifying biomarkers for better patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antagonists of PD-1 and PD-L1 in Cancer Treatment. Lipson, EJ., Forde, PM., Hammers, HJ., et al.[2022]

Blocking the PD-1/PD-L1 interaction has shown impressive antitumor effects, particularly in melanoma, with nivolumab demonstrating improved overall survival compared to traditional treatments like dacarbazine.

Combination therapies using PD-1 and CTLA-4 blockade can enhance response rates in patients less likely to respond to single-agent therapies, although they may also lead to increased immune-related adverse events that require careful management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Next Immune-Checkpoint Inhibitors: PD-1/PD-L1 Blockade in Melanoma. Mahoney, KM., Freeman, GJ., McDermott, DF.[2022]

In a study of 717 patients with resected stage III BRAF-mutant melanoma, those treated with adjuvant BRAF/MEK inhibitors showed better recurrence-free survival (RFS) at 12 months (85%) compared to those treated with anti-PD-1 (68%), although this difference was not observed at 18 months.

BRAF/MEK therapy had a high rate of early discontinuation (45.6%) due to toxicity, with 11.5% of patients experiencing grade ≥ 3 adverse effects, indicating that while BRAF/MEK may offer initial benefits, its safety profile raises concerns for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant BRAF-MEK Inhibitors versus Anti PD-1 Therapy in Stage III Melanoma: A Propensity-Matched Outcome Analysis. De Meza, MM., Blokx, WAM., Bonenkamp, JJ., et al.[2023]

TSAxCD28 bispecific antibodies can enhance the effectiveness of anti-PD-1 therapy, enabling immune responses and long-term memory against tumors that typically do not respond to PD-1 blockers, as demonstrated in preclinical models.

These bispecifics show minimal toxicity compared to other T cell activators, making them a promising and safe addition to cancer immunotherapy regimens, potentially improving outcomes for patients with resistant tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-targeted CD28 bispecific antibodies enhance the antitumor efficacy of PD-1 immunotherapy. Waite, JC., Wang, B., Haber, L., et al.[2021]

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 tribodies (TR0304 and TR0506) demonstrated similar binding affinity to their targets as existing monoclonal antibodies but showed enhanced lymphocyte activation and greater in vitro cytotoxicity against tumor cells compared to traditional combination therapies.

These tribodies may offer advantages over conventional treatments, including lower production costs and reduced dosage requirements, making them promising candidates for treating cancer patients who are resistant to current therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comparison of the Antitumor Efficacy of Novel Multi-Specific Tribodies with Combinations of Approved Immunomodulatory Antibodies. Manna, L., Rapuano Lembo, R., Yoshioka, A., et al.[2023]

ABL501, a bispecific antibody targeting both LAG-3 and PD-L1, enhances T cell activation more effectively than using single antibodies, leading to improved immune responses against tumors.

In preclinical models, ABL501 demonstrated strong antitumor efficacy and is currently being evaluated in a first-in-human clinical trial, indicating its potential as a novel cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LAG-3xPD-L1 bispecific antibody potentiates antitumor responses of T cells through dendritic cell activation. Sung, E., Ko, M., Won, JY., et al.[2023]

The combination of LAG-3 and PD-1 blockade, specifically using relatlimab and nivolumab, is being investigated as a promising new treatment approach for melanoma.

Two clinical trials have been conducted to evaluate the effectiveness of this combination therapy in patients with metastatic and high-risk, node-positive melanoma, indicating a potential advancement in melanoma treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relatlimab and nivolumab in the treatment of melanoma. Au, L., Larkin, J., Turajlic, S.[2023]

Citations

1. nature.com nature.com/articles/s41591-025-03967-2

the randomized phase 1b/2 Morpheus-Melanoma trial In phase 2/3 trials, concurrent checkpoint inhibition of PD-1 and LAG-3 led to an improved progression-free survival versus PD-1 inhibition ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04140500

NCT04140500 | Dose Escalation Study of a PD1-LAG3 ... 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 ...

3. 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 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10357068/

The introduction of LAG-3 checkpoint blockade in melanoma LAG-3 inhibition in combination with PD-1 inhibition offered impressive efficacy with modest increases in toxicity over single agent PD-1 inhibitor.

5. curemelanoma.org curemelanoma.org/blog/clinical-trials-to-watch-july-2025

Melanoma Clinical Trials to Watch: July 2025 Combinations of anti-PD1 drugs with other immune checkpoint drugs have been tested to see if they have better anti-tumor killing activity ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)02722-3/fulltext

745P Clinical activity, safety, and PK/PD from the first in ... RO7247669 is a novel, PD1-LAG3 bispecific antibody which delivers dual checkpoint inhibition through monovalent high affinity binding to PD-1, and monovalent ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40993242/

the randomized phase 1b/2 Morpheus-Melanoma trial Tobemstomig demonstrated improved safety versus nivolumab plus ipilimumab, with 2.5% (1/40) and 22.7% (5/22) of patients experiencing grade 3 or ...

8. clinicaltrial.be clinicaltrial.be/en/details/60499?per_page=20&only_recruiting=0&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_eligible=0&only_active=0

Dose Escalation Study of a PD1-LAG3 Bispecific Antibody i... Participants will receive RO7247669 every 2 weeks (Q2W) or every 3 weeks (Q3W) up to the maximum tolerated dose (MTD) until disease progression, ...