Triple Drug Combo for Advanced Cancer

Palo Alto (17 mi)

Overseen byTimothy A Yap

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: National Cancer Institute (NCI)

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?This phase Ib trial studies side effects and best dose of copanlisib and olaparib when given together with durvalumab, and how well they work in treating patients with solid tumors that has spread from where it first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving combinations of copanlisib and olaparib or copanlisib, olaparib, and durvalumab may work better in treating patients with solid tumors compared to usual treatments such as surgery, radiation, or other chemotherapy drugs.

Eligibility Criteria

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.

Inclusion Criteria

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

My heart's pumping ability is normal or above.

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

I am 18 years old or older.

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

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

I am 18 years old or older.

My tumor can be easily biopsied.

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

My cancer has specific genetic changes recognized by experts.

I am mostly active and can carry out light work.

Exclusion Criteria

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

I have severe heart disease.

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

I am allergic to certain cancer drugs or their ingredients.

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

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

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

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

I am currently pregnant or breastfeeding.

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

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

I have or had an autoimmune or inflammatory disorder.

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

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

I have unstable chest pain.

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

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

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

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

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

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

Treatment Details

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.

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.