IMM60 + Pembrolizumab for Melanoma

No longer recruiting at 15 trial locations

Overseen By Portage Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: iOx Therapeutics

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Cardiac conditions, Active malignancy, Transplant, CNS metastases, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, IMM60 (an experimental treatment), alone or combined with pembrolizumab (also known as KEYTRUDA, an immunotherapy drug), for individuals with advanced melanoma or non-small cell lung cancer (NSCLC). The goal is to determine if these treatments are safe and effective in halting cancer progression. The trial seeks participants with specific types of melanoma or stage IV NSCLC, who lack certain genetic mutations and have a measurable tumor. This offers an opportunity to try cutting-edge therapies that might improve outcomes for these cancers. As a Phase 1 and Phase 2 trial, the research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, providing a chance to be among the first to benefit from these innovative therapies.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that IMM60, both alone and with pembrolizumab, has been safe in earlier studies. These studies found no major safety problems when patients took IMM60. The combination with pembrolizumab was also well-tolerated, with most patients experiencing no serious side effects.

Pembrolizumab is already approved for treating cancers like melanoma and has been safely used in many patients. It is known to help people live longer with manageable side effects.

Based on current data, IMM60 and its combination with pembrolizumab appear to be safe for people. However, since this trial is partly in an early phase, the full safety profile is still under investigation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore a novel approach for treating melanoma. Unlike traditional therapies, IMM60 is a unique agent that may stimulate the immune system to better recognize and attack cancer cells. Pembrolizumab, a well-known immunotherapy, works by blocking the PD-1 pathway, which cancers often exploit to avoid detection by the immune system. The combination of IMM60 and pembrolizumab aims to enhance the body's natural defenses against melanoma, potentially offering more effective outcomes than current therapies alone. This innovative approach could pave the way for more powerful and targeted cancer treatments.

What evidence suggests that this trial's treatments could be effective for melanoma and non-small cell lung cancer?

Research shows that pembrolizumab effectively treats advanced melanoma. Studies indicate that it helps many patients live longer, with 62% surviving at least one year and 24% showing a positive response to the treatment. In this trial, some participants will receive pembrolizumab alone, while others will receive a combination of pembrolizumab and a new treatment called IMM60. Early results for the combination appear encouraging but remain limited. IMM60 aims to enhance the effects of pembrolizumab. The goal is to improve treatment outcomes for patients with melanoma and non-small cell lung cancer. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with advanced melanoma or stage IV non-small cell lung cancer (NSCLC) who are in good physical condition, have at least one measurable lesion, and proper organ function. NSCLC patients must not have certain gene mutations and need a PD-L1 assessment. Melanoma patients require known BRAF mutation status. Participants must agree to contraception use.

Inclusion Criteria

I agree to use contraception and not donate sperm for 120 days after my last treatment dose.

My NSCLC has been tested for PD-L1 levels.

I have a tumor that can be measured and has not been treated with radiation.

Exclusion Criteria

I have received an organ or tissue transplant from another person.

You have a prolonged QT interval, uncontrolled high blood pressure, moderate or severe heart failure, or recent heart attack or frequent chest pain.

I have or had lung inflammation that needed steroids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Dose Finding

Initial safety assessment and dose finding for IMM60 alone and in combination with pembrolizumab

Up to 6 cycles (each cycle is 3 weeks)

Every 3 weeks

Phase 2: Randomized Treatment

Participants receive IMM60 + pembrolizumab or pembrolizumab alone to assess progression-free survival

Up to 35 cycles (each cycle is 3 weeks)

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months after last participant enrolled

What Are the Treatments Tested in This Trial?

Interventions

• IMM60
• Pembrolizumab

Trial Overview The study tests IMM60 alone or combined with pembrolizumab on participants with melanoma or NSCLC. Phase 1 focuses on safety and finding the right dose of IMM60. Phase 2 compares the effectiveness of IMM60 plus pembrolizumab against pembrolizumab alone in improving survival without disease progression after 12 months.

How Is the Trial Designed?

Group I: Phase 2 PD-L1 ≥50% NSCLC Cohort 1 (Randomized, IMM60 + pembrolizumab) Experimental Treatment 2 Interventions

Pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles will be administered in combination with IMM60 IV every 3 weeks for up to 6 cycles. The IMM60 dose will be determined based on the results of the Phase 1 dose escalation safety cohorts.

Group II: Phase 2 PD-L1 <1% NSCLC Cohort 2 Experimental Treatment 2 Interventions

Participants will be treated with one cycle of IMM60 with a tumor biopsy before and after, to determine any changes in PD-L1 expression. After this one cycle, the participants will receive the combination of IMM60 IV for up to 6 total cycles + pembrolizumab 200 mg every 3 weeks administered IV. The IMM60 dose will be determined based on the results of the Phase 1 dose escalation cohorts.

Group III: Phase 1 IMM60 dose escalation safety arm Experimental Treatment 1 Intervention

3 dose levels of IMM60 will be assessed (1, 3, 9 and 36 mg/m\^2 administered IV every 3 weeks for up to 6 cycles)

Group IV: Phase 1 IMM60 + pembrolizumab combination safety arm Experimental Treatment 2 Interventions

Pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles will be administered in combination with IMM60 IV every 3 weeks for up to 6 cycles. The IMM60 dose will be determined based on the results of the IMM60 dose escalation safety cohort.

Group V: Melanoma Cohort Experimental Treatment 1 Intervention

IMM60 IV every 3 weeks for up to 6 cycles. The IMM60 dose will be determined based on the results of the Phase 1 dose escalation cohorts.

Group VI: Phase 2 PD-L1 ≥50% NSCLC Cohort 1 (Randomized, pembrolizumab monotherapy) Active Control 1 Intervention

Pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles.

Who Is Running the Clinical Trial?

iOx Therapeutics

Lead Sponsor

Trials

1

Recruited

1+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

In a study of 88 advanced melanoma patients treated with pembrolizumab, 81.8% experienced any-grade toxicities, with skin and gastrointestinal issues being the most common side effects.

Despite the high incidence of side effects, pembrolizumab was found to be well tolerated in real-world settings, and severe toxicities were manageable with systemic steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with pembrolizumab toxicities in advanced melanoma patients: a single-center experience in the UK. So, AC., Board, RE.[2022]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a post hoc analysis of the KEYNOTE-006 study involving 555 patients with advanced melanoma, both ipilimumab and BRAF ± MEK inhibitors showed antitumor activity as subsequent therapies after pembrolizumab, with overall response rates (ORR) of 17.5% for ipilimumab and 30.5% for BRAF ± MEK inhibitors.

Patients who had not previously received BRAF ± MEK inhibitors showed a significantly higher ORR of 43.2% when treated with these agents after pembrolizumab, indicating that prior treatment status may influence the effectiveness of subsequent therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of ipilimumab or BRAF ± MEK inhibition after pembrolizumab treatment in patients with advanced melanoma: analysis from KEYNOTE-006. Long, GV., Arance, A., Mortier, L., et al.[2022]

Pembrolizumab (Keytruda) is an effective treatment for advanced melanoma, showing significant improvements in progression-free survival and overall response rates compared to ipilimumab and chemotherapy in clinical trials involving patients with varying treatment histories.

The drug has a manageable safety profile, with immune-related side effects that are generally reversible, making it a valuable option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. Deeks, ED.[2022]

Pembrolizumab (PEM) significantly improved short-term treatment effectiveness and long-term survival rates in patients with advanced cutaneous malignant melanoma compared to chemotherapy with Temozolomide, with a notable increase in one-year survival rates (53.85% vs. 40.00%).

The use of PEM did not lead to a higher incidence of adverse reactions compared to the control group, indicating that it is a relatively safe treatment option for patients with this type of melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical application effect of Pembrolizumab in the treatment of advanced cutaneous malignant melanoma. Fu, L., Zhang, H., Jiang, J., et al.[2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.2582

A phase 1 first-in-human dose finding/randomized ... The study seeks to assess the safety and efficacy of IMM-60 alone and in combination with PEM. Results: 5 subjects have been enrolled in the ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05709821

IMM60 and Pembrolizumab in Melanoma and NSCLC The goal of this clinical trial is to learn about IMM60 with or without pembrolizumab in participants with advanced melanoma or non-small cell lung cancer.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37937397/

Real-world outcomes with immuno-oncology therapies in ... The OPTIMIzE study shows that immunotherapy is effective and tolerable for patients with advanced melanoma in the real-world setting.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0959804924017660

Improved survival of advanced melanoma patients ... Melanoma patients who received concomitant anticoagulation during their ICI treatment had a significantly improved outcome when compared to the reference group, ...

5. dana-farber.org dana-farber.org/newsroom/news-releases/2024/long-term-metastatic-melanoma-survival-dramatically-improves-on-immunotherapy

Long-term Metastatic Melanoma Survival Dramatically ... Half of patients with metastatic melanoma treated with a combination of immune checkpoint inhibitors survive cancer-free for 10 years or more.

6. onclive.com onclive.com/view/nk-t-cell-agonist-under-investigation-in-combination-with-pembrolizumab-in-melanoma-and-nsclc

NK T-Cell Agonist Under Investigation in Combination With ... The main findings we've seen preclinically are that IMM60 can have a direct effect upon tumor cells. Preclinical work shows activity directly ...

7. isrctn.com isrctn.com/pdf/80472712

Testing IMM60 in combination with pembrolizumab in ... The TMG will also review safety data and permit proceeding to the phase 2 component if safe to do so. Planned arms in the Phase 2 component ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12454464/

Real-World Outcomes of Pembrolizumab in Advanced ... The primary objectives were to assess real-world survival, treatment persistence, and safety outcomes for patients initiating pembrolizumab for ...