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Anti-metabolites

Azacitidine + Pembrolizumab for Melanoma

Phase 2

Waitlist Available

Led By Hussein Tawbi, MD, PHD

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

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

Must have

Age >/= 18 years at the time of signing informed consent

Patients who have not received prior PD-1 directed therapy (Arm A) or have progressed despite prior PD-1 directed therapy (Arm B)

Must not have

Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment

Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not recovered from adverse events

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial is for people with advanced melanoma who have been treated with ipilimumab and, if their disease progressed, a BRAF or MEK inhibitor.

Who is the study for?

This study is for adults with advanced melanoma who haven't had PD-1 therapy (Arm A) or have worsened despite it (Arm B). Participants need functioning organs, measurable disease, and must not be pregnant or breastfeeding. They should agree to use birth control and provide a tissue sample from the tumor. Those with active infections, recent other cancer treatments, certain heart diseases, CNS metastases, or immunodeficiency can't join.

What is being tested?

The trial investigates if combining oral azacitidine (CC-486) with pembrolizumab (MK-3475) can control advanced melanoma and studies the safety of this mix. Both drugs are FDA approved separately; their combination for treating melanoma is experimental. Up to 71 participants at MD Anderson will receive these drugs to see how well they work together.

What are the potential side effects?

Potential side effects include reactions related to immune system activation such as inflammation in various organs, infusion-related reactions like fever or chills, fatigue, possible blood disorders including changes in white cell counts leading to increased infection risk.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years old or older.

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I have never had PD-1 therapy (Arm A) or my cancer got worse despite it (Arm B).

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I am fully active or restricted in physically strenuous activity but can do light work.

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My melanoma cannot be removed by surgery and is in stage III or IV.

Exclusion Criteria

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

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I haven't taken steroids or immunosuppressants in the last 7 days.

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I haven't had chemotherapy, targeted therapy, or radiation in the last 2 weeks.

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I am currently being treated for an infection.

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I have not received a live vaccine in the last 30 days.

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I have been diagnosed with HIV.

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I have not had serious heart problems in the last 6 months.

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I have an active tuberculosis infection.

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I have a history of or currently have non-infectious lung inflammation.

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I have an active Hepatitis B or C infection.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Objective Response Rate in Participants with Metastatic Melanoma That Are PD-1 Naïve (Arm A) or That Have Progressed on PD-1 Directed Therapy (Arm B)

Secondary study objectives

Overall Survival in Participants with Metastatic Melanoma That Are PD-1 Naïve (Arm A) or That Have Progressed on PD-1 Directed Therapy (Arm B)

Progression Free Survival in Participants with Metastatic Melanoma That Are PD-1 Naïve (Arm A) or That Have Progressed on PD-1 Directed Therapy (Arm B)

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

Clostridium difficile colitis

Systemic infection

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

Placebo + CRT Followed by Placebo

Pembrolizumab + CRT Followed by Pembrolizumab

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm B: Metastatic Melanoma - Post PD-1 ProgressionExperimental Treatment2 Interventions

Thirty-five participants with metastatic melanoma that have progressed on PD-1 directed therapy enrolled in treatment Arm B. Treatment consists of 3-week cycles and continues until disease progression. Oral Azacitidine administered by mouth daily for 15 days (Days 1-15) of every cycle. Pembrolizumab administered by vein every 3 weeks and after the oral dose of Azacitidine on concurrent treatment days.

Group II: Arm A: Metastatic Melanoma - PD-1 NaiveExperimental Treatment2 Interventions

Thirty-six participants with metastatic melanoma that are PD-1 naïve enrolled in treatment Arm A. Treatment consists of 3-week cycles and continues until disease progression. Oral Azacitidine administered by mouth daily for 15 days (Days 1-15) of every cycle. Pembrolizumab administered by vein every 3 weeks and after the oral dose of Azacitidine on concurrent treatment days.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Azacitidine

2012

Completed Phase 3

~1440

Pembrolizumab

2017

Completed Phase 3

~3150