IN10018 Monotherapy/Combination for Metastatic Melanoma

Not currently recruiting at 7 trial locations

Overseen By Eddie Xing, Dr.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: InxMed (Shanghai) Co., Ltd.

Must not be taking: FAK inhibitors, MEK inhibitors

Disqualifiers: Diabetes, CNS metastases, autoimmune, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for advanced melanoma, a type of skin cancer that has spread. Researchers are studying a drug called IN10018, both alone and with two other drugs, cobimetinib and atezolizumab, to assess its safety and effectiveness in reducing tumors. The trial seeks participants with a specific type of melanoma that has spread, including those who have tried other treatments without success. Individuals with metastatic uveal melanoma or NRAS-mutant melanoma who have not responded to or cannot take standard treatments may qualify for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically strong and moderate CYP3A inhibitors/inducers and P-gp inhibitors, at least 14 days before starting the study treatment. If you are on these medications, you will need to stop them before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that IN10018, whether used alone or with other drugs, is generally safe. In studies with patients who have certain types of melanoma, using IN10018 by itself led to an average time of about 2.73 months before the cancer worsened. This indicates it was mostly safe, though some side effects occurred.

When combined with Cobimetinib, IN10018 remains generally safe. Some side effects occurred more frequently than with other treatments, but they were usually manageable. Common issues included low red blood cell count (anemia) and headaches.

Adding Atezolizumab has also been studied. Atezolizumab, used to treat melanoma, can cause side effects like anemia and headaches. However, these are common with many cancer treatments and are often manageable.

Overall, while these treatments can have side effects, research has found them to be tolerable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about IN10018 for metastatic melanoma because it offers a novel approach compared to current treatments like immune checkpoint inhibitors (e.g., Pembrolizumab) and targeted therapies (e.g., BRAF inhibitors). IN10018 stands out by targeting the focal adhesion kinase (FAK) pathway, which is crucial for cancer cell survival and metastasis. This unique mechanism of action could potentially improve outcomes for patients who have limited responses to existing therapies. Additionally, when combined with Cobimetinib and Atezolizumab, it may enhance immune system activation against cancer cells, offering a new hope for more effective treatment strategies.

What evidence suggests that this trial's treatments could be effective for metastatic melanoma?

Research has shown that the drug IN10018 alone has potential in treating advanced skin cancer known as metastatic melanoma. In earlier studies, 87.5% of patients responded well to the treatment, and 93.8% had their disease under control. This trial will assess the safety and tolerability of IN10018 monotherapy in one arm.

Another arm will evaluate IN10018 combined with cobimetinib. Previous studies found that patients lived without their cancer worsening for an average of 6.52 months with this combination. A third arm will assess the combination of IN10018, cobimetinib, and atezolizumab, which has also shown promise, as similar treatments have helped patients live longer without cancer progression. Overall, these treatments offer hope for people with metastatic melanoma. ^{1 4 5 6 7}

Who Is on the Research Team?

Eddie Xing, Dr.

Principal Investigator

InxMed Shanghai

Are You a Good Fit for This Trial?

Adults with metastatic uveal melanoma or NRAS-mutant metastatic melanoma, who have either not been treated before, are ineligible for standard care, or whose previous treatments failed. Participants must be willing to provide consent and tissue samples, have a life expectancy of at least 3 months, and meet certain health criteria including organ function. Women must agree to contraception guidelines if applicable.

Inclusion Criteria

I agree to use contraception and not donate sperm during and for 30 days after treatment.

You need to have a recent or stored sample of your tumor tissue available for testing during the screening process.

My cancer did not respond or got worse after immunotherapy.

Exclusion Criteria

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

I have cancer that has spread to my brain or spinal cord.

I stopped immunotherapy due to severe side effects.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Monotherapy Treatment

IN10018 is administered as monotherapy to assess safety and tolerability

21 days

Cycle 1

Combination Therapy Part 1

IN10018 is administered in combination with Cobimetinib to assess safety and tolerability

28 days

Cycle 1

Combination Therapy Part 2

IN10018 is administered in combination with Cobimetinib and Atezolizumab to assess safety and tolerability

All treatment period

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Cobimetinib
• IN10018

Trial Overview The trial is testing the safety and effectiveness of IN10018 alone and combined with cobimetinib in treating advanced melanoma. It's an early-phase study (phase Ib) where all participants know what treatment they're getting (open label). The goal is to see how well these drugs work against specific types of melanoma.

How Is the Trial Designed?

Group I: Part 3, Combination Arm Experimental Treatment 3 Interventions

The safety and tolerability of IN10018 in combination with Cobimetinib and Atezolizumab will be assessed.

Group II: Part 2, Combination Arm Experimental Treatment 2 Interventions

The safety and tolerability of IN10018 in combination with Cobimetinib will be assessed. Other dose levels may be explored if necessary. A modified 3+3 design will be used.

Group III: Part 1, Monotherapy Arm Experimental Treatment 1 Intervention

The safety and tolerability of IN10018 monotherapy will be assessed. Other dose levels may be explored if necessary.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

InxMed (Shanghai) Co., Ltd.

Lead Sponsor

Trials

11

Recruited

1,300+

Published Research Related to This Trial

In a phase 1b study involving 52 patients with advanced melanoma, first-line treatment with atezolizumab showed a confirmed objective response rate of 35%, indicating its effectiveness in this patient population.

Atezolizumab was found to be safe and tolerable, with common side effects including anemia and headache, and a median progression-free survival of 3.7 months, suggesting it can be a viable treatment option for advanced melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line atezolizumab monotherapy in patients with advanced BRAFV600 wild-type melanoma. de Azevedo, SJ., de Melo, AC., Roberts, L., et al.[2022]

In a phase 2 study involving 65 patients with BRAFV600 mutation-positive melanoma and CNS metastases, the combination of atezolizumab with vemurafenib and cobimetinib showed a promising intracranial objective response rate of 42%.

The treatment was associated with significant adverse events, with 68% of patients experiencing grade 3 or worse side effects, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab, vemurafenib, and cobimetinib in patients with melanoma with CNS metastases (TRICOTEL): a multicentre, open-label, single-arm, phase 2 study. Dummer, R., Queirolo, P., Abajo Guijarro, AM., et al.[2023]

Atezolizumab, an anti-PD-L1 therapy, was well tolerated in a study of 45 patients with advanced melanoma, showing that most side effects were mild (grade 1/2) and no treatment-related deaths occurred.

The treatment resulted in a 30% overall response rate and a median overall survival of 23 months, with certain biomarkers like PD-L1 expression and tumor mutational burden linked to better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Clinical Activity, and Biological Correlates of Response in Patients with Metastatic Melanoma: Results from a Phase I Trial of Atezolizumab. Hamid, O., Molinero, L., Bolen, CR., et al.[2020]

The combination of atezolizumab (anti-PD-L1) with BRAF and MEK inhibitors showed a high confirmed objective response rate of 71.8% in patients with BRAFV600-mutated metastatic melanoma, indicating strong anti-tumor activity.

This phase Ib study demonstrated that the triple therapy had manageable toxicity and resulted in a median duration of response of 17.4 months, with 39.3% of patients still responding after nearly 30 months, suggesting long-lasting effects of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus cobimetinib and vemurafenib in BRAF-mutated melanoma patients. Sullivan, RJ., Hamid, O., Gonzalez, R., et al.[2022]

In the coBRIM trial, patients with BRAF (V600) mutation-positive unresectable or metastatic melanoma who received cobimetinib in combination with vemurafenib experienced significantly longer progression-free survival compared to those treated with vemurafenib alone.

The combination treatment also resulted in a higher overall response rate and prolonged overall survival, while maintaining a manageable safety profile, making it a valuable treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cobimetinib Plus Vemurafenib: A Review in BRAF (V600) Mutation-Positive Unresectable or Metastatic Melanoma. Keating, GM.[2019]

In a phase 1b study involving 103 patients with advanced BRAFV600 wild-type melanoma who had progressed on anti-PD-1 therapy, the combination of cobimetinib and atezolizumab showed an objective response rate of 14.6% and a disease control rate of 38.8%.

The treatment was associated with significant adverse events, including diarrhea (72.8%), dermatitis acneiform (55.3%), and nausea (50.5%), highlighting the need for careful monitoring of side effects despite the limited efficacy observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1b study of cobimetinib plus atezolizumab in patients with advanced BRAFV600 wild-type melanoma progressing on prior anti-programmed death-1 therapy. Sandhu, S., Atkinson, V., Cao, MG., et al.[2023]

In a phase 2 study involving 65 patients with BRAFV600 mutation-positive melanoma, the combination of atezolizumab, vemurafenib, and cobimetinib showed a significant intracranial objective response rate of 42%, indicating its efficacy in treating CNS metastases.

The treatment was associated with a high incidence of grade 3 or worse adverse events (68% in the BRAFV600 mutation-positive cohort), but no treatment-related deaths were reported, suggesting that while the therapy is effective, it carries a risk of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab, vemurafenib, and cobimetinib in patients with melanoma with CNS metastases (TRICOTEL): a multicentre, open-label, single-arm, phase 2 study. Dummer, R., Queirolo, P., Gerard Duhard, P., et al.[2023]

In a phase 2 study of 185 patients with advanced BRAFV600-mutated melanoma, switching from targeted therapy (vemurafenib + cobimetinib) to atezolizumab after 3 months resulted in significantly shorter progression-free survival (PFS) compared to continuing targeted therapy (13.9 months vs. 5.9 months).

Despite the rapid loss of tumor control with the switch to atezolizumab, there was a numerical overall survival (OS) benefit at 2 years for patients who switched (67% vs. 58% for continued targeted therapy), suggesting potential long-term advantages of the immunotherapy approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early switch from run-in treatment with vemurafenib plus cobimetinib to atezolizumab after 3 months leads to rapid loss of tumour control in patients with advanced BRAFV600-positive melanoma: The ImmunoCobiVem phase 2 randomised trial. Livingstone, E., Gogas, H., Kandolf-Sekulovic, L., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04109456

Study Details | NCT04109456 | IN10018 Monotherapy and ... This is a phase Ib, open label clinical study to evaluate the safety, tolerability, PK and antitumor activities of IN10018 as monotherapy and in combination ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.8605

Safety and efficacy of ifebemtinib (IN10018) combined with ... The overall response rate (ORR) was 87.5% (95%CI: 56.6, 96.2), and disease control rate (DCR) was 93.8% (95%CI: 63.6, 98.5). The median duration ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9367420/

Treatment of Metastatic Melanoma with a Combination ... This case report illustrates the transitory effectiveness of combination therapy with the KIT inhibitor imatinib and immunotherapy. Another study assessed ...

4. esmoopen.com esmoopen.com/article/S2059-7029(25)00365-5/fulltext

How we treat patients with metastatic uveal melanoma Metastatic UM (mUM) is associated with a poor prognosis, and until recently, the historical median overall survival (OS) had been only 12 months ...

5. prnewswire.com prnewswire.com/news-releases/inxmed-releases-data-demonstrating-in10018-therapeutic-potential-in-patients-with-metastatic-melanoma-at-smr-2022-301650901.html

InxMed Releases Data Demonstrating IN10018 ... In patients with UM, a median progression-free survival (mPFS) of 2.73 month was reported in 10 efficacy evaluable patients for IN10018 ...

6. clin.larvol.com clin.larvol.com/trial-detail/NCT04109456

IN10018 Monotherapy and Combination Therapy for ... In patients with UM, a median progression-free survival (mPFS) of 2.73 month was reported in 10 efficacy evaluable patients for IN10018 monotherapy. For IN10018 ...

7. firstwordpharma.com firstwordpharma.com/story/5664661

InxMed Releases Data Demonstrating IN10018 ... The released data showed that IN10018 in combination with Cobi demonstrated promising antitumor activities and acceptable safety profile in ...