What is the mechanism of action of this treatment?

Immune checkpoint inhibitors, such as Anti-LAG-3 (e.g., Fianlimab) and Anti-PD-1 (e.g., Cemiplimab), are pivotal in treating melanoma by enhancing the body's immune response against cancer cells. Anti-PD-1 inhibitors block the programmed cell death-1 (PD-1) receptor on T cells, preventing cancer cells from evading immune detection. Anti-LAG-3 inhibitors target the lymphocyte-activation gene 3 (LAG-3) protein, further boosting T cell activity. These mechanisms are crucial for melanoma patients as they can lead to more effective and sustained immune responses, potentially improving survival rates and quality of life.

What side effects are associated with this type of intervention?

Common side effects of immune checkpoint inhibitors used in melanoma treatment, such as Anti-PD-1 (e.g., nivolumab, pembrolizumab) and Anti-CTLA-4 (e.g., ipilimumab), include fatigue, skin reactions (rash, pruritus), and gastrointestinal issues (diarrhea, colitis). More severe but less common side effects can involve endocrine disorders (hypothyroidism, adrenal insufficiency), liver toxicity (hepatitis), and lung inflammation (pneumonitis). These side effects are generally manageable with immunosuppressive treatments like corticosteroids.

What prior FDA approvals exist?

The FDA has approved several immune checkpoint inhibitors for the treatment of melanoma. Pembrolizumab (Keytruda) and Nivolumab (Opdivo) are both anti-PD-1 therapies that have shown significant efficacy in treating advanced melanoma. Ipilimumab (Yervoy), an anti-CTLA-4 therapy, has also been approved and is often used in combination with Nivolumab for enhanced effectiveness. Cemiplimab (Libtayo), another anti-PD-1 therapy, has been approved for various cancers, including melanoma. These approvals highlight the effectiveness of targeting immune checkpoints in melanoma treatment.

What other types of research exist?

Promising novel alternatives to Fianlimab and Cemiplimab for melanoma patients include: <ol> <li>Ipilimumab (Anti-CTLA-4) in combination with Nivolumab (Anti-PD-1), which has shown efficacy in various cancers including melanoma.</li> <li></li> </ol> Pembrolizumab (Anti-PD-1), which is already approved for melanoma and continues to be a strong option. 3. Avelumab (Anti-PD-L1), which has shown durable responses in clinical trials. 4. Talimogene laherparepvec (T-VEC) combined with Pembrolizumab, which has shown promise in advanced melanoma. 5. Experimental therapies such as CAR-T cell therapies and other novel immune checkpoint inhibitors targeting different pathways.

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Monoclonal Antibodies

Fianlimab + Cemiplimab for Melanoma

Phase 3

Recruiting

Research Sponsored by Regeneron Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients with histologically confirmed unresectable Stage III and Stage IV (metastatic) melanoma who have not received prior systemic therapy for advanced unresectable disease

Age ≥12 years on the date of providing informed consent

Must not have

Uveal melanoma

Unknown v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation status as described in the protocol

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline to end of study, approximately 6 years

Awards & highlights

Pivotal Trial

Summary

This trial is testing two new drugs, fianlimab and cemiplimab, to treat melanoma skin cancer. It examines their effectiveness and how they work in both teenagers and adults. The drugs help the immune system fight cancer cells.

Who is the study for?

Adolescents and adults with advanced melanoma that hasn't spread too much can join this trial. They should be over 12 years old, have a life expectancy of at least 3 months, and not have had previous systemic treatments for their condition. People with certain types of melanoma or those who are immunocompromised can't participate.

What is being tested?

The study is testing if combining two drugs, Fianlimab and Cemiplimab, works better than Pembrolizumab alone in stopping the cancer from progressing. It also looks at overall survival rates, response to treatment, safety in young people (12-18), quality of life impacts, and how the body processes the drugs.

What are the potential side effects?

Possible side effects include immune system reactions that could affect organs or cause infections; infusion-related reactions; fatigue; skin issues like rash; hormonal imbalances requiring hormone therapy; digestive problems such as diarrhea or liver inflammation.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have advanced melanoma that cannot be surgically removed and haven't received systemic therapy for it.

Select...

I am 12 years old or older.

Select...

I am mostly active and can carry out daily activities without significant assistance.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have been diagnosed with uveal melanoma.

Select...

I don't know my cancer's BRAF V600 mutation status.

Select...

I do not have an uncontrolled HIV, HBV, or HCV infection or a related immunodeficiency.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline to end of study, approximately 6 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline to end of study, approximately 6 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to end of study, approximately 6 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression-free survival (PFS)

Secondary study objectives

Change in GHS/QoL per EORTC QLQ-C30

Change in global health status/quality of life (GHS/QoL) per EORTC QLQ-C30

Change in physical functioning per EORTC QLQ-C30

+13 more

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Dysgeusia

33%

Vomiting

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Hypoacusis

20%

Alanine aminotransferase increased

20%

Hyponatraemia

19%

Tinnitus

19%

Oral candidiasis

19%

Asthenia

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hyperthyroidism

10%

Hypoalbuminaemia

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Neck pain

Peripheral sensory neuropathy

Gastrooesophageal reflux disease

Hiccups

Hyperglycaemia

Hyperuricaemia

Dizziness

Hypophosphataemia

Urinary tract infection

Ear pain

Localised oedema

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Sepsis

Pneumonia aspiration

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Systemic infection

Clostridium difficile colitis

Cardiac arrest

Death

Bronchitis

Hepatitis

Immune-mediated hepatitis

Oesophagitis

General physical health deterioration

Hypophagia

Tumour haemorrhage

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Colitis

Mouth haemorrhage

Hypersensitivity

Acute myocardial infarction

Abscess neck

Device related infection

Stoma site infection

Vascular device infection

Wound infection

Hypercalcaemia

Pulmonary embolism

Respiratory failure

100%

80%

60%

40%

20%

Study treatment Arm

Pembrolizumab + CRT Followed by Pembrolizumab

Placebo + CRT Followed by Placebo

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

4Treatment groups

Experimental Treatment

Group I: C: cemiplimab+placeboExperimental Treatment2 Interventions

As defined in Protocol Amendment 5

Group II: B: pembrolizumab+placeboExperimental Treatment2 Interventions

As defined in Protocol Amendment 5

Group III: A: fianlimab+cemiplimab dose 1Experimental Treatment2 Interventions

As defined in Protocol Amendment 5

Group IV: A1: fianlimab+cemiplimab dose 2Experimental Treatment2 Interventions

As defined in Protocol Amendment 5

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Placebo

1995

Completed Phase 3

~2670

Cemiplimab

2015

Completed Phase 3

~1470

Pembrolizumab

2017

Completed Phase 3

~3130

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Immune checkpoint inhibitors, such as Anti-LAG-3 (e.g., Fianlimab) and Anti-PD-1 (e.g., Cemiplimab), are pivotal in treating melanoma by enhancing the body's immune response against cancer cells. Anti-PD-1 inhibitors block the programmed cell death-1 (PD-1) receptor on T cells, preventing cancer cells from evading immune detection. Anti-LAG-3 inhibitors target the lymphocyte-activation gene 3 (LAG-3) protein, further boosting T cell activity. These mechanisms are crucial for melanoma patients as they can lead to more effective and sustained immune responses, potentially improving survival rates and quality of life.

Clinical studies with anti-CTLA-4 antibodies in non-melanoma indications.