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PI3K inhibitor

Triple Drug Combo for Advanced Cancer

Phase 1

Waitlist Available

Led By Timothy A Yap

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

GFR >= 51 mL/min, based on a 24-hour urine test for creatinine clearance or estimated using the Cockcroft-Gault equation

LVEF >= 50%

Must not have

Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of investigational product (IP)

New York Heart Association class III or IV heart disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the side effects and best dose of copanlisib and olaparib when given together with durvalumab, and how well they work in treating patients with metastatic or unresectable solid tumors.

Who is the study for?

This trial is for adults with advanced solid tumors that have spread or can't be removed by surgery, and who haven't responded to standard treatments. Participants must have specific gene mutations (like BRCA1/2 or PTEN), meet certain blood and organ function criteria, not be pregnant or breastfeeding, agree to use contraception if of childbearing potential, and cannot have had certain recent treatments or uncontrolled illnesses.

What is being tested?

The trial tests a combination of three anti-cancer drugs: Copanlisib (blocks enzymes for cell growth), Olaparib (stops tumor cells from repairing DNA damage), and Durvalumab (helps the immune system attack cancer). It aims to find the best dose with acceptable side effects and see if this combo works better than current treatments.

What are the potential side effects?

Potential side effects include reactions related to the immune system attacking normal organs, infusion-related reactions from drug administration, fatigue, digestive issues like nausea or diarrhea, changes in blood counts leading to increased infection risk or bleeding problems. Specific risks will vary based on individual patient health.

Eligibility Criteria

Inclusion Criteria

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

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My kidney function, measured by GFR, is 51 mL/min or higher.

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My heart's pumping ability is normal or above.

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I am mostly self-sufficient and can carry out daily activities.

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I am 18 years old or older.

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My hemoglobin level is at least 10 g/dL without recent blood transfusions.

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My cancer has spread, cannot be surgically removed, and standard treatments are not effective.

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I am 18 years old or older.

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My tumor can be easily biopsied.

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My cancer has specific genetic changes in DDR, PTEN, or PIK3CA genes.

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My cancer has specific genetic changes recognized by experts.

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I am mostly active and can carry out light work.

Exclusion Criteria

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

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I have not had major surgery within the last 28 days.

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I have severe heart disease.

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I have had a bone marrow or cord blood transplant in the past.

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I am allergic to certain cancer drugs or their ingredients.

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I haven't had chemotherapy or radiotherapy (except for comfort care) in the last 3 weeks.

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I am not taking strong drugs that affect liver enzyme activity.

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I have a wound, ulcer, or bone fracture that hasn't healed.

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I have lasting side effects from cancer treatment, but not hair loss.

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I am currently pregnant or breastfeeding.

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I haven't taken high-dose steroids or other immune-weakening drugs in the last 14 days.

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I cannot take pills by mouth or have a condition that affects how my body absorbs medication.

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I have or had an autoimmune or inflammatory disorder.

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I do not have a serious infection worse than a moderate level.

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I have previously received treatments targeting PD-1, PD-L1, or CTLA-4.

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I have unstable chest pain.

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I have cancer that has spread to my brain or spinal cord.

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I have been diagnosed with MDS/AML or my bone marrow shows signs of these conditions.

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I do not have an active infection needing IV antibiotics or any severe illness requiring hospitalization.

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I had another cancer but was treated successfully over 5 years ago with no signs of it returning.

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I have not had major surgery in the last 2 weeks or have fully recovered from one.

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I do not have any severe illnesses that my doctors are still trying to get under control.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 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

Maximum-tolerated dose (MTD) of copanlisib and olaparib

Secondary study objectives

Copy number variation profile

Duration of response

Immune-modulatory changes

+8 more

Side effects data

From 2022 Phase 2 trial • 80 Patients • NCT03015129

65%

Fatigue

63%

Abdominal pain

55%

Diarrhea

43%

Pain

40%

Weight loss

35%

Hypertension

30%

Anorexia

30%

Constipation

28%

Nausea

28%

Pruritus

25%

Vomiting

20%

Dyspnea

20%

Urinary tract infection

18%

Rash maculo-papular

15%

Cough

15%

Abdominal Pain

15%

Back pain

15%

Increased Urinary Frequency

15%

Weight gain

13%

Arthralgia

10%

Dizziness

10%

Anxiety

10%

Bladder infection

10%

Nasal congestion

10%

Vaginal discharge

Colitis

Dry mouth

Dry skin

Fever

Anal pain

Edema limbs

Flatulence

Headache

Hot flashes

Myalgia

Small intestinal obstruction

Thromboembolic event

Urinary frequency

Urinary tract pain

Confusion

Renal and urinary disorders - Other, specify

Adrenal insufficiency

Anemia

Ascites

Gastroesophageal reflux disease

Hypomagnesemia

Lymphedema

Memory impairment

Mucositis oral

Pneumonitis

Rash acneiform

Sinus bradycardia

Upper respiratory infection

Urinary urgency

Vaginal hemorrhage

Alanine aminotransferase increased

Aspartate aminotransferase increased

Alkaline phosphatase increased

Colonic perforation

Dysarthria

Blood bilirubin increased

CPK increased

Creatinine increased

Myositis

Rectal hemorrhage

Hypothyroidism

Left ventricular systolic dysfunction

Lethargy

Muscle weakness left-sided

Myocarditis

Rectal pain

Weight Loss

Fall

Generalized muscle weakness

Hyperglycemia

Hyperkalemia

Pain in extremity

Peripheral sensory neuropathy

Pleural effusion

Skin infection

100%

80%

60%

40%

20%

Study treatment Arm

Durvalubmab

Durvalubmab + Tremelimumab

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: Treatment (copanlisib hydrochloride, olaparib, and durvalumab)Experimental Treatment9 Interventions

Patients receive copanlisib hydrochloride IV over 1 hour on days 1 and 15 or days 1, 8, and 15 depending on dose level and olaparib PO BID on days 1-28 of each cycle. Beginning cycle 2, patients receive durvalumab IV over 1 hour on day 1 of each cycle. Cycles repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples at baseline within 7 days of C1D1, days 8 and 15 of cycle 1 and day 15 of subsequent cycles, at time of restaging, and end of treatment/progression. Patients undergo x-ray, CT, and MRI at the end of cycle 2 and then every 8 weeks. Patients also undergo an ECHO during pre-study within 28 days of C1D1 and tumor biopsy at baseline within 7 days of C1D1 and day 15 of cycle 1 or 2, and may undergo an optional biopsy at end of treatment/progression.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biopsy

2014

Completed Phase 4

~1150

Magnetic Resonance Imaging

2017

Completed Phase 3

~1180