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PI3K inhibitor

Copanlisib + Nivolumab + Ipilimumab for Advanced Cancers

Phase 1

Waitlist Available

Led By A P Chen

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

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

Must have

Age >= 18 years

Patients who have had prior monoclonal antibody therapy must have completed that therapy >= 6 weeks (or 3 half-lives of the antibody, whichever is shorter) prior to enrollment on protocol (minimum of 1 week between prior therapy and study enrollment)

Must not have

Human immunodeficiency virus (HIV)-positive patients are eligible if on stable dose of highly active antiretroviral therapy (HAART), no clinically significant drug-drug interactions are anticipated with the current HAART regimen, and viral load is undetectable. Patients on HAART regimens that include CYP3A4 inhibitors (e.g. ritonavir or cobicistat) are excluded. All patients must be screened for HIV up to 28 days prior to enrollment

Patients with clinically significant illnesses which would compromise participation in the study, including but not limited to active or uncontrolled infection, immune deficiencies, hepatitis B, hepatitis C, active tuberculosis, uncontrolled asthma, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, myocardial infarction within the past 6 months, cerebral vascular accident/stroke within the past 6 months, or psychiatric illness/social situations that would limit compliance with study requirements

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 6 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the side effects and best dose of the drugs copanlisib and nivolumab when given together. It is also testing the side effects of copanlisib when given together with nivolumab and ipilimumab.

Who is the study for?

Adults with advanced solid tumors or lymphoma, who have tried at least one line of therapy without a cure available. They must have acceptable organ function and blood counts, not be on certain medications, agree to use contraception, and provide tissue samples for research. Excluded are those with significant illnesses or conditions like brain metastases, uncontrolled hypertension or diabetes, recent immunosuppressants use, known allergies to trial drugs, active autoimmune diseases requiring treatment within the past 3 months.

What is being tested?

The trial is testing how well patients tolerate the combination of Copanlisib (blocks tumor growth proteins) and Nivolumab (boosts immune system against cancer), as well as this duo plus Ipilimumab (another immune booster). It aims to find the best dose for Copanlisib when used with these immunotherapies in treating advanced cancers and lymphomas.

What are the potential side effects?

Potential side effects include reactions related to immune system activation such as inflammation in various organs including lungs (pneumonitis), liver issues from elevated enzymes/bilirubin levels; skin reactions; endocrine disorders like thyroid dysfunction; gastrointestinal symptoms like diarrhea; fatigue; increased risk of infections due to immune suppression.

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 finished my last monoclonal antibody therapy at least 6 weeks ago, or 3 half-lives of the antibody, whichever is shorter.

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My kidney function, measured by creatinine levels or clearance, is within the required range.

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I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

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

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I am HIV-positive, on stable HAART without CYP3A4 inhibitors, and have an undetectable viral load.

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I do not have any major health issues that would stop me from participating in the study.

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My blood pressure is consistently below 140/90 mm Hg.

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I have not had, nor am I planning to have, any organ or stem cell transplant.

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I am not taking any herbal medications except for vitamins.

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I am not on any anti-arrhythmic drugs except for beta blockers or digoxin.

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I have been screened for hepatitis B and C, and if positive, my viral load is undetectable.

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I have been tested for CMV within the last 28 days and my results were negative.

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I am allergic to certain cancer medications similar to copanlisib or nivolumab.

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I haven't had specific immune or gene therapies for my condition.

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I am not pregnant or breastfeeding.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 6 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 6 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 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

Incidence of adverse events

Recommended phase 2 dose of copanlisib and nivolumab combination

Other study objectives

Biomarkers of AKT inhibition, deoxyribonucleic acid damage (gammaH2AX, pNbs1, Rad51), apoptosis, and epithelial-mesenchymal transition assessed in pre- and post- treatment tumor biopsies

Markers of anti-tumor immunity assessed in circulating immune cells, circulating tumor cells, and pre- and post-treatment tumor biopsies

Preliminary antitumor activity

Side effects data

From 2021 Phase 2 trial • 24 Patients • NCT02631590

75%

Platelet count decreased

75%

Lymphocyte count decreased

71%

Fatigue

71%

White blood cell decreased

67%

Anemia

67%

Neutrophil count decreased

63%

Hypertension

54%

Hyperglycemia

50%

Nausea

46%

Diarrhea

46%

Lipase increased

46%

Anorexia

42%

Alanine aminotransferase increased

42%

Abdominal Pain

33%

Fever

29%

Hyponatremia

25%

Weight loss

25%

Dehydration

25%

Hyperkalemia

25%

Hypotension

25%

Vomiting

25%

Constipation

25%

Rash maculo-papular

21%

Edema limbs

21%

Aspartate aminotransferase increased

21%

Serum amylase increased

17%

Chills

17%

Pain

17%

Alkaline phosphatase increased

17%

Creatinine increased

17%

Thromboembolic event

17%

Sinus tachycardia

17%

Dizziness

13%

Pain in extremity

13%

Dyspnea

13%

Generalized muscle weakness

13%

Blood bilirubin increased

13%

Hypoalbuminemia

13%

Infusion related reaction

13%

Non-cardiac chest pain

13%

Gastrointestinal disorders - Other

13%

Mucositis oral

13%

Sepsis

13%

Upper respiratory infection

13%

Urinary tract infection

13%

Anxiety

13%

Tinnitus

Back pain

Cough

Pleural effusion

Hypoxia

Ascites

Neck pain

Insomnia

Gallbladder obstruction

Bloating

General disorders and administration site conditions -Other

Abdominal distension

Dysphagia

Pruritus

Rash acneiform

Peripheral sensory neuropathy

Infections and infestations - Other

Dysgeusia

Depression

Phlebitis

Neoplasms benign, malignant and unspecified - Other

Colitis

Colonic obstruction

Gastrointestinal disorders -Other

Cholecystitis

Dry mouth

Pancreatitis

Stomach pain

Toothache

Gait disturbance

Infusion site extravasation

Activated partial thromboplastin time prolonged

Blood antidiuretic hormone abnormal

Investigations - Other

Urine output decreased

Hypercalcemia

Hypernatremia

Hyperuricemia

Hypokalemia

Hypomagnesemia

Aspiration

Atelectasis

Epistaxis

Hiccups

Hoarseness

Nasal congestion

Pneumonitis

Postnasal drip

Productive cough

Sore throat

Wheezing

Bone pain

Paroxysmal atrial tachycardia

Pericarditis

Confusion

Acute kidney injury

Ear pain

Cataract

Dry eye

Fracture

Injury, poisoning and procedural complications - Other

Venous injury

Allergic reaction

Hepatic infection

Infections and Infestations - Other

Urinary tract obstruction

Lung infection

Gastroesophageal reflux disease

Malaise

Musculoskeletal and connective tissue disorders - Other

Skin ulceration

Headache

Parathesia

Gallbladder infection

Dry skin

Skin and subcutaneous tissue disorders - Other

Sinus bradycardia

Cystitis noninfective

Hematuria

Renal and urinary disorders - Other

Urine discoloration

100%

80%

60%

40%

20%

Study treatment Arm

Combination Therapy

Awards & Highlights

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Group I: Cohort III (Triplet) (copanlisib, nivolumab, ipilmumab)Experimental Treatment7 Interventions

Patients receive copanlisib IV over 1 hour on days 1, 8, and 15 of each cycle, nivolumab IV over 30 minutes on day 15 of cycle 1 and then day 1 of each subsequent cycles, and ipilimumab IV over 90 minutes on day 1 for cycles 2-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan and/or MRI throughout the trial. Patients undergo blood sample collection on study and during follow-up, as well as tumor biopsy on study. Patients also undergo an ECHO during screening and as clinically indicated on study.

Group II: Cohort II (Triplet Safety) (copanlisib, nivolumab, ipilimumab)Experimental Treatment8 Interventions

Patients receive copanlisib IV over 1 hour on days 1, 8, and 15 of each cycle, nivolumab IV over 30 minutes on day 1 of each cycle, and ipilimumab IV over 90 minutes on day 1 for cycles 1-4. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan and/or MRI throughout the trial. Patients undergo an ECHO during screening and as clinically indicated on study.

Group III: Cohort I (Doublet) (copanlisib, nivolumab)Experimental Treatment7 Interventions

Patients receive copanlisib IV over 1 hour on days 1 and 15 or days 1, 8, and 15 of each cycle and nivolumab IV over 30 minutes on day 1 or days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan and/or MRI throughout the trial. Patients undergo blood sample collection on study and during follow-up, as well as tumor biopsy on study. Patients also undergo an ECHO during screening and as clinically indicated on study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Echocardiography

2013

Completed Phase 4

~11580

Biopsy

2014

Completed Phase 4

~1150