Alintegimod + Ipilimumab + Nivolumab for Cancer

Recruiting at 3 trial locations

Overseen By VP Clinical Affairs and Regulatory

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: 7 Hills Pharma, LLC

Must not be taking: CYP3A inhibitors, Immunosuppressants

Disqualifiers: Active brain metastasis, Cardiac conditions, HIV, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

126 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a new combination of drugs, including alintegimod (an experimental treatment), ipilimumab, and nivolumab, can treat certain advanced or metastatic cancers. The focus is on cancers like melanoma, lung cancer, and others that might respond well to these medications. Participants should have one of these cancers and not have certain medical conditions, such as active brain metastasis or untreated autoimmune diseases. The study aims to determine the safest and most effective doses for these drugs to manage these cancers. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you should avoid medications that strongly affect liver enzymes (CYP3A) within 2 weeks before starting the trial. It's best to discuss your current medications with the trial team.

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

Research has shown that Alintegimod is generally well-tolerated when used alone in healthy volunteers. In one study, 36 out of 48 participants took Alintegimod without major problems. In contrast, Ipilimumab, another drug in this trial, has caused serious side effects in about 26% of people during past treatments. Discussing these possible side effects with a doctor is important.

Nivolumab, the third treatment in this trial, is usually well-tolerated. About 15% of patients have reported immune-related issues, and a small number, around 7%, stopped treatment due to side effects. These figures suggest that most people manage Nivolumab well.

For those considering joining this trial, understanding the history of these treatments is crucial. Always discuss personal health situations with a healthcare professional to make the best choice. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Alintegimod, Ipilimumab, and Nivolumab for cancer treatment because it offers a unique multi-faceted approach. Unlike traditional treatments that primarily rely on chemotherapy, this combination leverages the body's own immune system to fight cancer. Alintegimod, a novel component, is believed to enhance immune response, potentially leading to more effective results when paired with Ipilimumab and Nivolumab, which are known immune checkpoint inhibitors. This approach could offer patients a more targeted therapy with potentially fewer side effects compared to conventional treatments.

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

Research has shown that Alintegimod can increase T cell activity, crucial for the immune system, in lab tests and improve survival in cancer models. This suggests it might help the body fight cancer more effectively. In this trial, participants will receive Alintegimod in a dose escalation phase, with some receiving it as monotherapy and others in combination with Ipilimumab and Nivolumab. Studies on Ipilimumab, often used with Nivolumab, have demonstrated long-term survival benefits for various cancers, such as melanoma and kidney cancer. Specifically, using Ipilimumab and Nivolumab together has led to higher survival rates and a lower risk of death in patients with certain cancers. These treatments aim to boost the immune system's ability to fight cancer cells, offering hope for better outcomes. ^{1 2 3 6 7}

Who Is on the Research Team?

Lionel Lewis, MA, MB.Bch, MD

Principal Investigator

7 Hills Pharma

Are You a Good Fit for This Trial?

This trial is for adults with various advanced cancers, including skin, kidney, liver cancer, and more. Participants must have a specific genetic feature (like Lynch Syndrome) or high levels of certain proteins. Pregnant women and those with autoimmune diseases or other conditions that could interfere with the study are excluded.

Inclusion Criteria

Has a life expectancy of > 12 weeks

My kidney function is good.

All patients must have measurable disease by applicable RECIST criteria

Exclusion Criteria

Previous participation in a study of any investigational agent within 21 days of enrollment or within 5 half-lives of the study treatment

Any condition that may compromise patient's participation in the trial

Patients with known soy allergy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation - Open Label Phase 1b

Alintegimod dose escalation with 3 cohorts, followed by Alintegimod monotherapy for 1 cycle, Alintegimod + Ipilimumab for 4 cycles, and Nivolumab for 11 cycles

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Alintegimod
• Ipilimumab
• Nivolumab

Trial Overview The trial is testing Alintegimod combined with Ipilimumab followed by Nivolumab alone in two parts: Phase 1b to find safe doses and Phase 2a to compare this combo against standard treatments. It's an open-label study initially but will become blinded later on.

How Is the Trial Designed?

Group I: Dose Escalation - Open Label Phase 1b Experimental Treatment 3 Interventions

Alintegimod dose escalation, 4 cohorts Alintegimod monotherapy 1 cycle Alintegimod + Ipilimumab - 4 cycles Nivolumab - 11 cycles

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

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

7 Hills Pharma, LLC

Lead Sponsor

Trials

2

Recruited

190+

Published Research Related to This Trial

In a review of 129 oncology patients treated with immune checkpoint inhibitors, 51.9% experienced at least one immune-related adverse event (irAE), highlighting the common occurrence of these side effects.

Nearly half of the irAEs were managed according to established guidelines, but there was significant variability in documentation and management practices, indicating a need for improved adherence as immunotherapy use increases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Adherence to Toxicity Management Guidelines for Immune-Related Adverse Events. Teimouri, A., Minard, LV., Scott, SN., et al.[2022]

Combining nivolumab and ipilimumab shows improved effectiveness in treating metastatic melanoma compared to using either drug alone, based on a retrospective analysis of approximately 7700 patients.

The combination therapy presents a safety profile that includes immune-related adverse events from both drugs, indicating that while the combination is effective, it also carries a heightened risk of toxicity that needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. Soldatos, TG., Dimitrakopoulou-Strauss, A., Larribere, L., et al.[2022]

In a phase 2 trial involving 142 patients with untreated advanced melanoma, the combination of nivolumab and ipilimumab resulted in a 2-year overall survival rate of 63.8%, compared to 53.6% for those receiving ipilimumab alone, suggesting improved survival outcomes with the combination therapy.

However, the combination treatment was associated with a higher incidence of severe side effects, with 54% of patients experiencing grade 3-4 adverse events compared to 20% in the ipilimumab-only group, indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Hodi, FS., Chesney, J., Pavlick, AC., et al.[2022]

In a study of 1255 patients with metastatic non-small cell lung cancer (NSCLC), first-line treatment with nivolumab plus ipilimumab (NIVO+IPI) showed a high incidence of treatment-related adverse events (TRAEs), with 78% experiencing any-grade TRAEs and 34% experiencing severe (grade 3 or 4) TRAEs, but the treatment was generally well tolerated.

Patients who discontinued NIVO+IPI due to TRAEs still had a favorable long-term survival rate, with a 3-year overall survival of 50%, indicating that stopping treatment because of side effects did not negatively impact their long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. Paz-Ares, LG., Ciuleanu, TE., Pluzanski, A., et al.[2023]

Combining nivolumab with ipilimumab results in higher response rates in cancer treatment compared to using nivolumab alone, indicating a potentially more effective therapeutic strategy.

This combination therapy may enhance the immune response against cancer, but specific details on the number of subjects or study duration are not provided in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus Ipilimumab Achieves Responses in dMMR/MSI-H Tumors. [2019]

In a study analyzing 2,088 individual case safety reports (ICSRs) related to immune checkpoint inhibitors (ICIs) in Italy, 801 reports documented serious immune-related adverse drug reactions (irADRs), primarily affecting male patients with gastrointestinal and skin toxicities.

Among the ICIs, nivolumab and pembrolizumab were most frequently associated with irADRs, with significant risks identified for pembrolizumab and ipilimumab, highlighting the need for oncologists to recognize and manage these serious side effects effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors and Immune-Related Adverse Drug Reactions: Data From Italian Pharmacovigilance Database. Ruggiero, R., Fraenza, F., Scavone, C., et al.[2022]

In the Asian subpopulation with advanced non-small cell lung cancer (NSCLC) and PD-L1 expression ≥1%, patients treated with nivolumab plus ipilimumab showed significantly improved overall survival (OS) and progression-free survival (PFS) compared to those receiving chemotherapy, with a 3-year OS rate of 53% versus 37%.

The safety profile of nivolumab plus ipilimumab was manageable, with grade 3-4 treatment-related adverse events occurring in 40% of patients, similar to the 36% in the chemotherapy group, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. O'Byrne, KJ., Lee, KH., Kim, SW., et al.[2022]

In a phase 3 trial involving 1150 patients with advanced non-small-cell lung cancer (NSCLC), the combination of nivolumab and ipilimumab with two cycles of chemotherapy significantly improved overall survival compared to chemotherapy alone, with a median survival of 15.6 months versus 10.9 months.

The treatment regimen showed a favorable safety profile, with serious treatment-related adverse events occurring in 30% of the experimental group compared to 18% in the control group, indicating that the benefits of the combination therapy outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Paz-Ares, L., Ciuleanu, TE., Cobo, M., et al.[2021]

In a phase 2 trial involving 117 patients with advanced, refractory squamous non-small-cell lung cancer, nivolumab demonstrated a 14.5% objective response rate, indicating its potential effectiveness as a treatment option.

The safety profile of nivolumab was manageable, with 17% of patients experiencing severe treatment-related adverse events, suggesting that while there are risks, the benefits may outweigh them for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Rizvi, NA., Mazières, J., Planchard, D., et al.[2022]

In a pooled analysis of 1332 patients with advanced non-small-cell lung cancer (NSCLC), the combination of nivolumab and ipilimumab showed a median overall survival (OS) of 18.6 months and a 3-year OS rate of 35%, indicating significant long-term survival benefits compared to traditional chemotherapy.

The study found that patients who responded to treatment at 6 months had markedly better survival rates, with a 3-year OS of 66% for responders, highlighting the importance of early response in predicting long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. Borghaei, H., Ciuleanu, TE., Lee, JS., et al.[2023]

Nivolumab is a PD-1 immune checkpoint inhibitor that effectively enhances antitumor immunity by blocking the PD-1 receptor on activated T cells, which helps reverse immune suppression in cancer patients.

Clinical trials have demonstrated the efficacy of nivolumab in treating various cancers, including non-small-cell lung cancer, melanoma, and renal cell carcinoma, making it a promising option in targeted immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab as Programmed Death-1 (PD-1) Inhibitor for Targeted Immunotherapy in Tumor. Guo, L., Zhang, H., Chen, B.[2022]

Nivolumab plus ipilimumab showed durable and long-term efficacy in treating advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, regardless of tumor PD-L1 expression levels.

These findings are based on updated results from part 1 of the phase 3 CheckMate 227 trial, indicating that this combination therapy could be a more effective frontline treatment option for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. Kahl, KL.[2021]

Nivolumab combined with ipilimumab significantly improves overall survival in adult patients with intermediate/poor-risk advanced renal cell carcinoma compared to sunitinib, with a hazard ratio of 0.63, indicating a 37% reduction in the risk of death.

In the study involving 1096 patients, the median overall survival was not reached for the nivolumab + ipilimumab group, while it was 25.95 months for the sunitinib group, highlighting the potential of this combination therapy for better long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European Medicines Agency extension of indication to include the combination immunotherapy cancer drug treatment with nivolumab (Opdivo) and ipilimumab (Yervoy) for adults with intermediate/poor-risk advanced renal cell carcinoma. Ali, S., Camarero, J., Hennik, P., et al.[2021]

In a phase 1b trial involving 137 patients with relapsed/refractory lymphoid malignancies, the combination of nivolumab with ipilimumab or lirilumab showed significant activity in classical Hodgkin lymphoma, with overall response rates of 74% and 76%, respectively.

However, the combination therapies did not demonstrate a meaningful improvement in efficacy compared to single-agent nivolumab, and the combination with ipilimumab resulted in higher rates of severe treatment-related adverse events (29%) compared to lirilumab (15%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1b study of dual PD-1 and CTLA-4 or KIR blockade in patients with relapsed/refractory lymphoid malignancies. Armand, P., Lesokhin, A., Borrello, I., et al.[2021]

In a meta-analysis of 2,946 cancer patients, the combination therapy of nivolumab and ipilimumab was found to significantly increase the risk of immune-related adverse events (irAEs) compared to nivolumab alone.

Patients receiving the combination therapy experienced higher rates of various irAEs, including skin reactions, gastrointestinal issues, and liver enzyme elevation, indicating a need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of immune-related adverse events associated with ipilimumab-plus-nivolumab and nivolumab therapy in cancer patients. Zhou, S., Khanal, S., Zhang, H.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06362369

NCT06362369 | A Study of Oral 7HP349 (Alintegimod) in ... This Phase study is designed to evaluate the safety, tolerability, and preliminary efficacy of oral Alintegimod (Alintegimod) alone, and then in combination ...

2. reporter.nih.gov reporter.nih.gov/search/AaFf1AX5pUy9xWJM8IFD0w/project-details/10761171

7HP349, an Integrin Activator to Treat Patients With anti-PD-1 ... 7HP349 shows augmented T cell activity in vitro, and enhanced antitumor efficacy and survival in tumor models, with increased T cell infiltration into tumors ...

3. jitc.bmj.com jitc.bmj.com/content/10/Suppl_2/A632

603 A randomized, placebo-controlled, first in human ... In B16 and CT26 syngeneic models 7HP349 monotherapy has anti-tumor efficacy and enhanced anti-CTLA-4 and anti-PD-1 tumoricidal effects. 7HP349 ...

4. cancernetwork.com cancernetwork.com/view/fast-track-designation-granted-to-novel-immunostimulant-7hp349-in-anti-pd-1-resistant-melanoma

Fast Track Designation Granted to Novel Immunostimulant ... The confirmed ORR in the investigational arm was 52.3% vs 46.6% in the chemotherapy · Camrelizumab/Famitinib Show First-Line PFS Benefit in ...

5. texasheart.org texasheart.org/7-hills-pharma-announces-first-patient-in-phase-1b-2a-clinical-trial-testing-alintegimod-against-apd-1-resistant-solid-tumors/

7 Hills Pharma Announces First Patient in Phase 1b/2a ... 7 Hills Pharma Inc. (7 Hills), a clinical-stage pharmaceutical company, announcing that their first cancer patient has been safely dosed with alintegimod.

6. onclive.com onclive.com/view/fda-grants-fast-track-status-to-7hp349-for-pd-1-resistant-metastatic-melanoma

FDA Grants Fast Track Status to 7HP349 for PD-1– ... Preclinical data have illustrated that these compounds can result in a 100-fold increase in the adhesion of activated T cells to simulated tumor ...

7. targetedonc.com targetedonc.com/view/fda-grants-fast-track-designation-to-7hp349-for-anti-pd-1-metastatic-melanoma

FDA Grants Fast Track Designation to 7HP349 for Anti-PD- ... The primary end point was safety and tolerability of 7HP349 with secondary end points including pharmacokinetics as assessed by maximum plasma ...