DYP688 for Metastatic Uveal Melanoma

Not currently recruiting at 11 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Novartis Pharmaceuticals

Must not be taking: Anticoagulants, Chemotherapy, Immuno-oncologics

Disqualifiers: Other malignancies, Active brain metastases, 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 explores a new treatment called DYP688 for individuals with metastatic uveal melanoma, a type of eye cancer that has spread. The study examines the safety and effectiveness of DYP688 in fighting tumors, particularly in those with specific genetic mutations (GNAQ/11). Participants may qualify if they have uveal melanoma that has spread, regardless of prior treatment with the drug tebentafusp, or if they have other melanomas with similar mutations. The trial seeks to find new options for those whose cancer hasn't responded to standard treatments. As a Phase 1, Phase 2 trial, this research focuses on understanding how DYP688 works in people and measuring its effectiveness in an initial group, offering participants a chance to access a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires stopping certain cancer treatments before starting the study drug. Specifically, you must stop fluoropyrimidine therapy 2 weeks before, radiation therapy 4 weeks before, and other cancer therapies like chemotherapy or immunotherapy 4 to 6 weeks before, depending on the type. The protocol does not specify about non-cancer medications, so you should discuss this with the study team.

Is there any evidence suggesting that DYP688 is likely to be safe for humans?

A previous study tested DYP688, a new treatment, on individuals with certain types of melanoma. The research showed that participants generally tolerated the treatment well in these initial trials. Some side effects occurred, but most were mild or moderate, meaning they were not severe and could be managed.

Since the study is in an early phase, it focuses on assessing the safety of DYP688 in humans. Early phase studies indicate that researchers are still learning about the treatment's safety. However, testing in humans suggests that initial lab tests were promising enough to proceed.

In summary, while some safety information is available, more research is needed to fully understand the safety of DYP688 for treating metastatic uveal melanoma and similar conditions. ^{1 2 3 4 5}

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

Most treatments for metastatic uveal melanoma involve immunotherapy or chemotherapy, which can have limited effectiveness for some patients. However, DYP688 is unique because it targets specific mutations in the GNAQ and GNA11 genes, which are common drivers of this cancer. This targeted approach could lead to more effective and personalized treatment options. Researchers are excited about DYP688 because it has the potential to improve outcomes for patients who don't respond well to current therapies and offers a new mechanism of action by specifically addressing genetic mutations.

What evidence suggests that DYP688 might be an effective treatment for metastatic uveal melanoma?

Research has shown that DYP688, which participants in this trial may receive, may help treat metastatic uveal melanoma (MUM) and other melanomas with GNAQ/11 mutations. In animal studies, DYP688 significantly reduced tumor size. This treatment targets cancer cells with these mutations, possibly stopping their growth. Early results suggest that DYP688 can lead to long-lasting tumor shrinkage, effectively reducing tumor size over time. Although more research is needed, these initial findings are promising for people with these types of melanomas. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for patients with metastatic uveal melanoma or other melanomas with GNAQ/11 mutations. Adults and, in some cases, children over 12 can join if they weigh at least 40 kg and are healthy enough (good performance status). They must be willing to undergo biopsies unless medically inadvisable. Patients should not have active brain metastases, significant bleeding risks, recent cancer treatments that could interfere, other cancers, severe allergies to similar drugs, or uncontrolled heart disease.

Inclusion Criteria

You have advanced uveal melanoma and have either not received treatment before or have tried other treatments that did not work. If you have non-uveal melanoma, it must have spread and not responded to standard treatments, and you must have a specific GNAQ/11 mutation.

For the phase II trial, patients with advanced uveal melanoma that has not responded to standard treatments or for whom there are no other treatment options may be eligible. Also, patients with certain mutations in cutaneous or mucosal melanomas and no other effective treatment options may be eligible.

I am mostly active and can care for myself regardless of my age.

Exclusion Criteria

I haven't had specific cancer treatments recently before starting the study treatment.

I do not have any cancer other than the one being treated in this study.

I have active brain metastases or leptomeningeal disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I: Dose Escalation

Dose escalation to determine the maximum tolerated dose (MTD) and/or recommended dose (RD) of DYP688 in patients with metastatic uveal melanoma and other GNAQ/11 mutant melanomas

9 months

Phase II: Treatment

Treatment of patients in different groups: tebentafusp-naïve, tebentafusp-pre-treated, and non-uveal melanoma based on emerging data

17 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• DYP688

Trial Overview The study is testing DYP688 as a single agent for its safety and effectiveness against certain types of advanced melanoma. It's an open-label trial meaning everyone knows what treatment they're getting. The first phase checks the right dose and the second phase sees how well it works on different groups including those who've had standard treatments or specific prior therapy.

How Is the Trial Designed?

Group I: Phase II: Tebe pre-treated Experimental Treatment 1 Intervention

Patients with metastatic uveal melanoma that have been previously treated with tebentafusp

Group II: Phase II: Tebe naive group Experimental Treatment 1 Intervention

Patients with metastatic uveal melanoma that has not received prior treatment with tebentafusp

Group III: Phase II: Non-uveal melanoma Experimental Treatment 1 Intervention

Optional Arm: To explore patients with non-uveal melanoma that harbor GNAQ or 11 mutations, based on emerging data from dose escalation

Group IV: Phase I: Dose Escalation Experimental Treatment 1 Intervention

Patients with metastatic uveal melanoma or other GNAQ/11 mutant melanomas

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.9509

A first-in-human study of DYP688, an antibody drug ... 9509Background: GNAQ/11 mutations occur in up to 95% of uveal melanomas (UM) and a subset of non-uveal melanomas.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05415072

NCT05415072 | A Phase I/II Study of DYP688 in Patients ... A Phase I/​II Study of DYP688 in Patients With Metastatic Uveal Melanoma and Other GNAQ/​11 Mutant Melanomas ... GNAQ/11 mutation based on local data. For ...

3. asco.org asco.org/abstracts-presentations/ABSTRACT484332

A first-in-human study of DYP688, an antibody drug ... ... metastatic uveal melanoma (MUM) and other GNAQ/11 mutant melanomas. A first-in-human study of DYP688, an antibody drug conjugate delivering a direct Gq/11 ...

4. aacrjournals.org aacrjournals.org/mct/article/23/12_Supplement/IA022/750259/Abstract-IA022-DYP688-a-first-in-class-PMEL17

Abstract IA022: DYP688, a first-in-class PMEL17-targeted ... In vivo, DYP688 exhibits marked and durable tumor regression in GNAQ/11-mutant UVM models, including patient-derived xenograft and liver ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05415072?cond=Uveal%20Melanoma,%20Metastatic&viewType=Table&rank=2

A Phase I/II Study of DYP688 in Patients With Metastatic ... A Phase I/​II Study of DYP688 in Patients With Metastatic Uveal Melanoma and Other GNAQ/​11 Mutant Melanomas ... GNAQ/11 mutation based on local data. For ...