BAY1895344 and Copanlisib for the Treatment of Molecularly Selected Patients With Advanced Solid Tumors

NCT05010096 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: 2020-0706NCI-2021-06215
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase Ib trial finds out the best dose, possible benefits and/or side effects of BAY1895344 and copanlisib in treating molecularly selected patients with solid tumors that have spread to other places in the body (advanced). BAY1895344 and copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving BAY1895344 and copanlisib together may help control the progression of the disease in patients with advanced solid tumors.

Conditions

Locally Advanced Malignant Solid Neoplasm; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Solid Neoplasm; Recurrent Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (AEs)

  Will assess the incidence and severity of AEs and serious AEs. Individual listings of AEs will be provided and coded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 dictionary if available. The incidence of treatment-emergent adverse events (TEAEs) and drug-related TEAEs, respectively, will be summarized by cohort and for the total study population in frequency tables using the CTCAE grade. Frequency tables will also be provided for the changes of worst CTCAE grade after the start of treatment versus baseline. In addition, the same analysis will be done using Medical Dictionary for Regulatory Activities terms. The incidence of laboratory toxicities will be summarized by worst CTCAE v5.0 grade and by cohort. Frequency tables will be provided for the changes of worst CTCAE grade after the start of treatment versus baseline.

  Up to 30 days after the last dose of study drug

• Incidence of dose limiting toxicities (DLTs)

  Severity of AEs will be graded according to the NCI CTCAE v 5.0.

  Up to 28 days

Secondary Outcomes (6)

• Objective response rate (ORR)

  Up to 2 years

• Clinical benefit rate (CBR)

  Up to 2 years

• Time to response

  Up to 2 years

• Duration of response

  Up to 2 years

• Progression free survival

  Up to 2 years

Study Arms (2)

Arm I (elimusertib, copanlisib)

EXPERIMENTAL

Patients receive Patients receive elimusertib PO BID on days 1-3 and 15-17, and copanlisib IV over 1 hour on days 4 and 18. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may continue to receive elimusertib PO BID and copanlisib IV at the discretion of the treating physician.

Drug: Copanlisib; Drug: Elimusertib

Arm II (elimusertib, copanlisib)

EXPERIMENTAL

Patients receive elimusertib PO BID on days 1-3 and 15-17, and copanlisib IV over 1 hour on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may continue to receive elimusertib PO BID and copanlisib IV at the discretion of the treating physician.

Drug: Copanlisib; Drug: Elimusertib

Interventions

Copanlisib DRUG

Given IV

Also known as: BAY 80-6946, PI3K Inhibitor BAY 80-6946

Arm I (elimusertib, copanlisib); Arm II (elimusertib, copanlisib)

Elimusertib DRUG

Given PO

Also known as: ATR Inhibitor BAY1895344, ATR Kinase Inhibitor BAY1895344, BAY 1895344, BAY-1895344, BAY1895344

Arm I (elimusertib, copanlisib); Arm II (elimusertib, copanlisib)

Eligibility Criteria

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

You may qualify if:

• DOSE ESCALATION: Patients must have a pathogenic or likely pathogenic germline or somatic defect as determined by local assessment and classification in at least one of the following:
• Defect in one or more DNA Damage Response (DDR) genes such as: ATM (including ATM protein loss by IHC), ATRX, ARID1A, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCM, MRE11A, MSH2, NBN, PALB2, RAD51, RAD51B, RAD51C, RAD51D, or other related genes at the discretion of the principal investigator in consultation with the MD Anderson Cancer Center Institute for Personalized Cancer Therapy Precision Oncology Decision Support (PODS) group OR
• PIK3CA hotspot and PTEN mutations
• DOSE EXPANSION: Patients must have a pathogenic or likely pathogenic germline or somatic defect as determined by local assessment and classification
• Cohort A: ATM deleterious mutation or loss of ATM expression
• Cohort B: Actionable PIK3CA hotspot and PTEN mutations
• Patients must have histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors (except primary central nervous system \[CNS\] tumors), that are not amenable form treatment with curative intent or who have refused or are intolerant of standard therapy
• Availability of a fresh or recent tumor tissue sample from a diagnostic biopsy/surgery or a metastatic tumor biopsy; the sample must have been obtained with 12 months prior to study enrollment. When only bone disease is present, an archival tumor tissue sample obtained within 5 years prior to study enrollment may be accepted for non-prostate cancer patients and a fresh bone biopsy may be accepted for prostate cancer patients only
• Patients must be \>=18 years of age
• Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1; or patients may have bone only metastatic disease evaluable by Prostate Cancer Working Group 3 (PCWG3) for subjects with metastatic castration-resistant prostate cancer (mCRPC), or according to the tumor evaluation criteria best suited and accepted for the tumor type being evaluated
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Absolute neutrophil count (ANC) \>= 1,500/mcL.
• Platelets \>= 150,000 / mcL
• Hemoglobin \>= 10 g/dL without dependence on erythropoietin support or blood product support
• Participants must not have received a transfusion (platelets or red blood cells) within 28 days of the first dose of study intervention. Participants must not have received administration of granulocyte colony-stimulating factor, erythropoietin, or thrombopoietic treatments within 14 days of the first dose of study intervention. Hemoglobin (Hb) value must be met without erythropoietin dependency

You may not qualify if:

• Inability or unwillingness to swallow pills
• Active infection requiring intravenous (IV) antibiotics or other uncontrolled intercurrent illness requiring hospitalization. Minor infections, e.g. periodontal infection or urinary tract infection (UTI), which may be treated with short term oral antibiotics are allowed
• History of cerebrovascular accident (CVA), myocardial infarction or unstable angina within the previous 6 months before starting therapy
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has a known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging (as determined by magnetic resonance imaging \[MRI\] or computed tomography \[CT\]) for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline) and have no evidence of new or enlarging brain metastases. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids \> 10mg or equivalent of prednisone for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
• Patients with uncontrolled Type I or II diabetes mellitus (DM); uncontrolled DM is defined as hemoglobin A1c (HbA1c) \> 8.5% and a fasting blood glucose of \> 120 mg/dL within 14 days prior to trial entry
• Patients with congestive heart failure \> New York Heart Association (NYHA) Class 2, unstable angina, or uncontrolled hypertension despite optimal management
• Patients with history or concurrent condition of interstitial lung disease or any severity and/or severely impaired lung function
• Patients with prior anti-cancer therapy within 2 weeks prior to study enrollment or prior radiation therapy within 2 weeks prior to study enrollment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided it has been completed at least 2 days prior to study enrollment and no clinically significant toxicities are expected (e.g. mucositis, esophagitis)
• Patients who have undergone major surgery and have not recovered prior to study enrollment
• Patients who have a known prior severe hypersensitivity to investigational products or any component in their formulations
• Patients with persisting toxicity related to prior therapy (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] v5.0 grade \> 1). However, alopecia and sensory neuropathy grade =\< 2, or other grade =\< 2 adverse events not constituting a safety risk, based on the investigator's judgement, are acceptable
• All participants must be screened for hepatitis B virus (HBV) and hepatitis C virus (HCV) up to 28 days prior to start of study intervention, using the routine hepatitis virus laboratorial panel.
• Participants positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) will be eligible if they are negative for HBV deoxyribonucleic acid (DNA); participants positive for anti-HCV will be eligible if they are negative for HCV ribonucleic acid (RNA)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

copanlisib; BAY 1895344

Condition Hierarchy (Ancestors)

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

Study Officials

• Timothy A Yap, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2021
• First Posted: August 18, 2021
• Study Start: March 22, 2022
• Primary Completion: March 22, 2022
• Study Completion: March 22, 2022
• Last Updated: May 27, 2022

Record last verified: 2022-05