Testing the Combination of the Anti-cancer Drugs Copanlisib, Olaparib, and MEDI4736 (Durvalumab) in Patients With Advanced Solid Tumors With Selected Mutations

NCT03842228 | Active Not Recruiting Phase 1 Results FDA Drug

• 4 other identifiers: NCI-2019-00601NCI1021710217UM1CA186688
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 17

Brief Summary

This phase Ib trial seeks to identify the side effects and best dose of the combination of copanlisib and olaparib when given together with durvalumab. The trial will evaluate how well the drug combinations work in treating patients with advanced cancers who have solid tumors that have spread from where they 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 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. The treatment 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.

Conditions

Advanced Malignant Solid Neoplasm; Unresectable Malignant Solid Neoplasm; Metastatic Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Dose Limiting Toxicities (DLT) as a Measure of Safety Profile to Determine Recommended Phase 2 Dose (RP2D)

  A DLT was evaluated according to the NCI CTCAE 5.0. An AE was defined as DLT if it met any of the following events: any grade 5 toxicity; any grade 2 toxicity that require permanent discontinuation of durvalumab or combination therapies within the first 4 weeks; grade 4 neutropenia; febrile neutropenia; neutropenic infection; grade ≥ 3 thrombocytopenia with bleeding; grade 4 thrombocytopenia; Grade 4 anemia; non-hematological grade ≥ 4 toxicities; confirmation of QTc prolongation; grade ≥3 AE hyperglycemia or hypertension lasting \< 7 days; grade 3 skin rash despite optimal medical intervention; grade 3 diarrhea despite optimal medical intervention; any toxicity greater than baseline \& clinically significant or unacceptable \& disrupts dosing for more than 14 days; any event, including significant dose reductions or omissions as judged by safety review committee; \& any toxicity in any course of treatment that in the opinion of the investigators and medical monitors is dose-limiting.

  The DLT monitoring time frame was Cycle 1 through Cycle 2 Day 1 for the doublet combination (SIL1, SIL2, SIL3, and SIL3A) , and Cycle 1 through Cycle 3 Day 1 for the triplet combination (S2L1)

Secondary Outcomes (6)

• Objective Response Rate (ORR = Complete Response [CR] + Partial [PR])

  Up to 2 years

• Duration of Response

  From time measurement criteria are met for CR or PR until the first date that recurrent or progressive disease is objectively documented, assessed up to 2 years

• Progression-free Survival

  From start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years

• Overall Survival

  Up to 2 years

• Pharmacokinetics of Copanlisib and Olaparib (Doublet Combination); Step 1 Cohorts

  Step 1: C1D8- baseline; 30 and 55 mins post start copanlisib(copa),1 hour (h), 3h, 5h, 7h, and 23h after end of copa; C1D15: baseline, 30 min, 55min post start copa infusion. Step 1 DL3A: only C1D15 timepoints.

Study Arms (1)

Treatment (copanlisib hydrochloride, olaparib, and durvalumab)

EXPERIMENTAL

See Detailed Description

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Copanlisib Hydrochloride; Biological: Durvalumab; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Drug: Olaparib; Procedure: X-Ray Imaging

Interventions

Biopsy Procedure PROCEDURE

Undergo tumor biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (copanlisib hydrochloride, olaparib, and durvalumab)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (copanlisib hydrochloride, olaparib, and durvalumab)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (copanlisib hydrochloride, olaparib, and durvalumab)

Copanlisib Hydrochloride DRUG

Given IV

Also known as: 5-Pyrimidinecarboxamide, 2-Amino-N-(2,3-dihydro-7-methoxy-8-(3-(4-morpholinyl)propoxy)imidazo(1,2-C)quinazolin-5-yl)-, Hydrochloride (1:2), Aliqopa, BAY 80-6946 Dihydrochloride, BAY-80-6946 Dihydrochloride, Copanlisib Dihydrochloride

Treatment (copanlisib hydrochloride, olaparib, and durvalumab)

Durvalumab BIOLOGICAL

Given IV

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI 4736, MEDI-4736, MEDI4736

Treatment (copanlisib hydrochloride, olaparib, and durvalumab)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Treatment (copanlisib hydrochloride, olaparib, and durvalumab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (copanlisib hydrochloride, olaparib, and durvalumab)

Olaparib DRUG

Given PO

Also known as: AZD 2281, AZD-2281, AZD2281, KU 0059436, KU-0059436, KU0059436, Lynparza, Olanib, Olaparix, PARP Inhibitor AZD2281

Treatment (copanlisib hydrochloride, olaparib, and durvalumab)

X-Ray Imaging PROCEDURE

Undergo x-ray

Also known as: Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographs, Radiographic Imaging, Radiographic imaging procedure (procedure), Radiography, RG, Static X-Ray, X-Ray

Treatment (copanlisib hydrochloride, olaparib, and durvalumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ELIGIBILITY CRITERIA FOR ENROLLMENT INTO STEPS 1, 2, AND 3
• Patients must have germline or somatic mutations in DDR genes: BARD1, BRCA1, BRCA2, BRIP1, FANCA, NBN, PALB2, RAD51, RAD51B, RAD51C, RAD51D; or actionable mutations in the PTEN gene, or hotspot mutations in the PIK3CA gene (E542, E545 or H1047 are accepted). Local testing in Clinical Laboratory Improvement Act (CLIA)-certified laboratory will be accepted. Only mutations that have been recognized as actionable by the MD Anderson Precision Oncology Decision Support (PODS) team will be accepted
• Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
• Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Patients must be \>= 3 weeks beyond treatment with any chemotherapy or \>= 4 weeks beyond treatment with other investigational therapy to include hormonal, biological, or targeted agents; or at least 5 half-lives from hormonal, biological, or targeted agents, whichever is shorter at the time of treatment initiation
• Age \>= 18 years. Because no dosing or adverse event (AE) data are currently available on the use of copanlisib in combination with olaparib +/- durvalumab (MEDI4736) in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
• Patients with a mutation within both the DDR and PTEN/PIK3CA pathways will be assessed by the genomics Precision Oncology Decision Support group at MD Anderson, and the patient will be allocated to the PI3K or DDR expansion group deemed to be the main driver. If the actionability between the groups is deemed to be equivocal, then the patient will be allocated to the expansion cohort with fewer patients
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) =\< 1 (Karnofsky \>= 60%)
• Hemoglobin \>= 10 g/dL with no blood transfusion in the past 28 days
• Leukocytes \>= 3,000/mcL
• Lipase =\< 1.5 x upper limit of normal (ULN)
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 140,000/mcL
• Total bilirubin =\< 1.5 x institutional ULN
• Serum bilirubin =\< 1.5 x institutional ULN

You may not qualify if:

• Persistent toxicities (\> Common Terminology Criteria for Adverse Events \[CTCAE\] grade 2) caused by previous cancer therapy, excluding alopecia
• Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
• Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
• Patients who are receiving any other investigational agents
• Other malignancy unless curatively treated with no evidence of disease for \>= 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), or stage 1, grade 1 endometrial carcinoma. A patient with a history of localized triple negative breast cancer may be eligible, provided the patient completed the adjuvant chemotherapy \> 3 years prior to registration, and the patient remains free of recurrent or metastatic disease
• Patients with myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) or with bone marrow findings consistent with MDS/AML
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib, copanlisib, PI3K inhibitors or MEDI4736 (durvalumab) or any of the excipients of any study products
• Concomitant use of strong CYP3A inhibitors and inducers
• Olaparib: concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period for strong or moderate CYP3A inhibitors prior to starting olaparib is 2 weeks
• Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• Concomitant use of known strong CYP3A inducers (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout period for strong or moderate CYP3A inducers prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents
• Copanlisib: copanlisib is primarily metabolized by CYP3A4. Therefore, the concomitant use of strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir), and strong inducers of CYP3A4 (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) are not permitted from 14 days prior to enrollment until the end of the study
• Other medications that are prohibited while on copanlisib treatment:
• Herbal medications/preparations (except for vitamins)
• Anti-arrhythmic therapy other than beta blockers or digoxin

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (17)

Keck Medicine of USC Buena Park

Buena Park, California, 90621, United States

Location

Keck Medicine of USC Koreatown

Los Angeles, California, 90020, United States

Location

Los Angeles General Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

USC Norris Oncology/Hematology-Newport Beach

Newport Beach, California, 92663, United States

Location

Keck Medical Center of USC Pasadena

Pasadena, California, 91105, United States

Location

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Texas at Austin

Austin, Texas, 78712, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555-0565, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Biopsy; Specimen Handling; copanlisib; durvalumab; Immunoglobulin G; Disulfides; Magnetic Resonance Spectroscopy; olaparib; X-Rays; Phantoms, Imaging

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Spectrum Analysis; Chemistry Techniques, Analytical; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Equipment and Supplies

Results Point of Contact

• Title: Dr. Timothy Yap
• Organization: The University of Texas MD Anderson Cancer Center

tyap@mdanderson.org

(713) 839-5458

Study Officials

• Timothy A Yap

  University of Texas MD Anderson Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2019
• First Posted: February 15, 2019
• Study Start: November 21, 2019
• Primary Completion: July 29, 2024
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 29, 2026
• Results First Posted: August 3, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (17)