RO7247669 for Melanoma

Recruiting at 31 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

93 Participants Needed

Trial Summary

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.

What data supports the idea that RO7247669 for Melanoma is an effective treatment?

The available research shows that treatments similar to RO7247669, which target both PD-1 and LAG-3, have shown promising results in enhancing the body's immune response against tumors. For example, one study found that a similar bispecific antibody increased the activity of immune cells and improved their ability to attack tumor cells. Another study demonstrated that these types of treatments could activate immune cells more effectively than using single-target drugs. Although the specific data for RO7247669 in melanoma is not provided, these findings suggest that targeting both PD-1 and LAG-3 could be a powerful approach in treating melanoma. ^{1 2 3 4 5}

What data supports the effectiveness of the drug RO7247669 for treating melanoma?

Research on similar bispecific antibodies, which target both PD-1 and LAG-3, shows that they can enhance the body's immune response against tumors. These antibodies have demonstrated stronger anti-tumor activity and increased activation of immune cells compared to using single-target antibodies, suggesting potential effectiveness for treatments like RO7247669. ^{2 3 4 5 6}

What safety data is available for RO7247669 in melanoma treatment?

The provided research does not specifically mention RO7247669 or its other names like Tobemstomig or Anti PD-1 anti LAG-3 bispecific antibody. The articles focus on PD-1 and PD-L1 inhibitors in general, such as nivolumab and pembrolizumab, which have shown acceptable tolerability and manageable safety profiles in melanoma treatment. However, specific safety data for RO7247669 is not available in the provided research. ^{7 8 9 10 11}

Is RO7247669 safe for humans?

The safety profile of drugs that block PD-1, like RO7247669, is generally considered manageable, making them suitable for outpatient use. These drugs have shown acceptable tolerability in patients with melanoma in clinical trials. ^{7 8 9 10 11}

Is the drug RO7247669 promising for treating melanoma?

Yes, the drug RO7247669 is promising for treating melanoma. It combines two powerful approaches to boost the immune system's ability to fight cancer. By targeting both PD-1 and LAG-3, it can potentially overcome resistance seen in other treatments and enhance the body's natural defenses against tumors. This dual action has shown strong anti-tumor effects in studies, making it a valuable candidate for further development in cancer therapy. ^{2 3 12 13 14}

What makes the drug RO7247669 unique for treating melanoma?

RO7247669 is unique because it is a bispecific antibody that targets both PD-1 and LAG-3, two proteins that can suppress the immune system's ability to fight cancer. This dual targeting approach may enhance the immune response against tumors more effectively than targeting each protein individually. ^{2 3 12 13 14}

What is the purpose of this trial?

The purpose of this study is to assess the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics of two dose levels of RO7247669 in participants with unresectable or metastatic melanoma to select the recommended dose for further development.

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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]

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]

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]

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]

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]

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]

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]

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]

References

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

Tumor-targeted CD28 bispecific antibodies enhance the antitumor efficacy of PD-1 immunotherapy. [2021]

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

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

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

FS118, a Bispecific Antibody Targeting LAG-3 and PD-L1, Enhances T-Cell Activation Resulting in Potent Antitumor Activity. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

A Comparison of the Antitumor Efficacy of Novel Multi-Specific Tribodies with Combinations of Approved Immunomodulatory Antibodies. [2023]

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

LAG-3xPD-L1 bispecific antibody potentiates antitumor responses of T cells through dendritic cell activation. [2023]

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

Antagonists of PD-1 and PD-L1 in Cancer Treatment. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Adjuvant anti-PD-1 antibody treatment in stage III/IV melanoma: real-world experience and health economic considerations. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Anti-PD1 and anti-PD-L1 in the treatment of metastatic melanoma. [2023]

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

The Next Immune-Checkpoint Inhibitors: PD-1/PD-L1 Blockade in Melanoma. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Adjuvant BRAF-MEK Inhibitors versus Anti PD-1 Therapy in Stage III Melanoma: A Propensity-Matched Outcome Analysis. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Fc-competent multispecific PDL-1/TIGIT/LAG-3 antibodies potentiate superior anti-tumor T cell response. [2023]

13. 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]

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

Relatlimab and nivolumab in the treatment of melanoma. [2023]