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PI3K Inhibitor

Duvelisib + Nivolumab for Melanoma

Phase 1 & 2

Waitlist Available

Led By John Kirkwood, MD

Research Sponsored by John Kirkwood

Eligibility Criteria Checklist

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

Must have

ECOG performance status ≤ 2 or Karnofsky ≥ 60%

Age ≥ 18 years

Must not have

Subjects who are unable or unwilling to take prophylaxis for Pneumocystis jirovecii, human simplex virus (HSV) or herpes zoster (VZV) at time of screening

Subject had therapy with radiation, surgery or chemotherapy within 4 weeks prior to time of consent and/or has not recovered from adverse events to due to prior therapy. Subjects should be adequately recovered from all toxicities, complications, or acute illnesses prior to starting investigational therapy.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline (prior to treatment), at 12 weeks after start of treatment; up to 2 years (cohort)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new combination therapy to treat advanced melanoma that has progressed after anti-PD1 therapy. The new therapy consists of two drugs, given orally and intravenously. The goal is to find the recommended dose of the oral drug and to see if the combination therapy can help the patient's disease from progressing.

Who is the study for?

Adults (18+) with advanced unresectable melanoma that worsened after anti-PD1 therapy can join. They must have measurable disease, be willing to use effective birth control, and have normal organ/bone marrow function. Excluded are those with significant infections, recent treatments, allergies to trial drugs, CNS metastases unless stable, autoimmune diseases except mild ones like type I diabetes or skin disorders not needing systemic treatment.

What is being tested?

The study tests a combination of oral duvelisib and intravenous nivolumab in patients with advanced melanoma who didn't respond to previous anti-PD1 therapy. The Phase I part determines the safe dose for Phase II where it's given up to one year or until disease progression or unacceptable side effects occur.

What are the potential side effects?

Potential side effects include immune-related issues such as inflammation in organs; reactions at the infusion site; fatigue; digestive problems; blood disorders; increased risk of infection; and possible harm to an unborn baby.

Eligibility Criteria

Inclusion Criteria

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

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I can take care of myself but might not be able to do heavy physical work.

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I am 18 years old or older.

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I have a tumor that can be measured and is at least 10mm in size.

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I am a woman capable of becoming pregnant.

Exclusion Criteria

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

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I cannot or will not take preventive medication for certain infections.

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I haven't had cancer treatment in the last 4 weeks and have recovered from any side effects.

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I do not have chronic liver issues, veno-occlusive disease, nor do I abuse alcohol or use illicit drugs, except for marijuana.

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I do not have serious heart problems.

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I cannot or do not want to have blood drawn from my veins.

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I am not allergic to duvelisib or its ingredients.

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I haven't taken strong CYP3A affecting drugs or certain foods in the last 2 weeks.

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I do not have uveal or mucosal melanoma.

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I have had severe lung inflammation or liver enzyme issues.

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I have been treated with PI3K inhibitors before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline (prior to treatment), at 12 weeks after start of treatment; up to 2 years (cohort)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline (prior to treatment), at 12 weeks after start of treatment; up to 2 years (cohort)

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline (prior to treatment), at 12 weeks after start of treatment; up to 2 years (cohort) for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Change in CD +8 TIL frequency

Nivolumab

Overall Response Rate (ORR)

Secondary study objectives

Adverse events graded by CTCAE v5.0

Clinical Benefit

Duration of Response

+3 more

Other study objectives

Immune Cell Function

Mechanism of anti-PD1 Resistance

Tumor Microenvironment (TME)

Side effects data

From 2021 Phase 3 trial • 319 Patients • NCT02004522

50%

Diarrhoea

34%

Neutropenia

29%

Pyrexia

25%

Anaemia

24%

Nausea

23%

Cough

17%

Thrombocytopenia

17%

Constipation

16%

Fatigue

16%

Pneumonia

15%

Vomiting

15%

Decreased appetite

14%

Upper respiratory tract infection

13%

Asthenia

13%

Colitis

13%

Weight decreased

13%

Bronchitis

11%

Abdominal pain

11%

Rash

10%

Hypokalaemia

10%

Oedema peripheral

Aspartate aminotransferase increased

Dyspnoea

Alanine aminotransferase increased

Back pain

Dizziness

Headache

Hypertension

Nasopharyngitis

Arthralgia

Pruritus

Hyperkalaemia

Respiratory tract infection

Rash maculo-papular

Febrile neutropenia

Rhinorrhoea

Dyspepsia

Pain in extremity

Abdominal pain upper

Dehydration

Insomnia

Productive cough

Dry mouth

Muscle spasms

Paraesthesia

Pneumonitis

Renal failure acute

Toxic skin eruption

Hypotension

General physical health deterioration

Gastroenteritis

Gastritis

Pneumonia pseudomonas aeruginosa

Pancytopenia

Cardiac failure

Sepsis

Pneumocystis jirovecii pneumonia

Pneumonia pneumococcal

Pulmonary embolism

Interstitial lung disease

Respiratory failure

Pneumonia aspiration

Pneumonia klebsiella

Urinary tract infection

Pneumonia staphylococcal

Pleural haemorrhage

Streptococcal sepsis

Skin infection

Rash erythematous

Accidental overdose

Fungal oesophagitis

Upper gastrointestinal haemorrhage

Proctitis

Enterocolitis

Mental impairment

Intestinal adenocarcinoma

Deep vein thrombosis

Haemolytic anaemia

Atrial fibrillation

Cardiac failure congestive

Myocardial infarction

Pericarditis

Death

Mucosal inflammation

Multi-organ failure

Sudden death

Transitional cell carcinoma

Bronchiolitis

Bronchitis viral

Bronchopneumonia

Cytomegalovirus colitis

Pneumonia escherichia

Pneumonia mycoplasmal

Septic shock

Streptococcal bacteraemia

Subdural haematoma

Lipase increased

Nephrolithiasis

Renal colic

Renal failure

Renal failure chronic

Lung disorder

Ventricular tachycardia

Colitis ischaemic

Enteritis

Pancreatitis acute

Ileal ulcer

Aspergillus infection

Bronchopulmonary aspergillosis

Campylobacter gastroenteritis

Clostridium difficile colitis

Fungal infection

Influenza

Pseudomonal sepsis

Lower respiratory tract infection

Pneumonia bacterial

Enterococcal infection

Enterococcal sepsis

Escherichia sepsis

Escherichia urinary tract infection

Gastroenteritis viral

Haemophilus infection

Infection

Infusion site cellulitis

Lobar pneumonia

Lower respiratory tract infection viral

Lung infection

Pneumonia respiratory syncytial viral

Pneumonia streptococcal

Pseudomonas bronchitis

Wound infection staphylococcal

Cervical vertebral fracture

Femur fracture

Traumatic haematoma

Malnutrition

Hyponatraemia

Tumour lysis syndrome

Arthritis

Bone pain

Malignant melanoma

Brain stem haemorrhage

Dementia

Acute respiratory distress syndrome

Acute respiratory failure

Chronic obstructive pulmonary disease

Dermatitis exfoliative

Thrombosis

Infusion related reaction

Neuroendocrine tumour

Pleural effusion

Mallory-Weiss syndrome

Diverticulitis

Pyelonephritis

Haemorrhagic stroke

Dermatitis allergic

Respiratory tract infection bacterial

Splenic rupture

Neuroendocrine carcinoma of the skin

100%

80%

60%

40%

20%

Study treatment Arm

Duvelisib

Ofatumumab

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Duvelisib plus NivolumabExperimental Treatment2 Interventions

Phase 1: Duvelisib will be taken orally in doses from 15mg once a day, 25mg once a day or 25mg twice a day, 12 hours a part, to determine the recommended dose for the Phase II study when combined with nivolumab. Nivolumab, 240mg, IV, every 2 weeks for the first four cycles; thereafter it may be switched to 480mg, IV, once every 4 weeks if deemed appropriate by the study doctor. Phase II: The Recommended Phase II dosage of duvelisib administered will not be determined until Phase I is completed. Nivolumab, 480mg, IV, every 4 weeks, for up to 1 year.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nivolumab

2014

Completed Phase 3

~5220

Duvelisib

2016

Completed Phase 3

~760