Clinical Trials /

An Study to Evaluate the Safety and Efficacy of Copanlisib in Combination With Nivolumab in Patients With Advanced Solid Tumors

NCT03735628

Description:

The purpose of the dose escalation part of this study is to determine the feasibility of using the combination of copanlisib and nivolumab in subjects with advanced solid tumors, and to determine the maximum tolerated dose of copanlisib in combination with nivolumab. The maximum tolerated dose will then be used in Phase 2 (dose expansion) of the study.

Related Conditions:
  • Colorectal Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: An Study to Evaluate the Safety and Efficacy of Copanlisib in Combination With Nivolumab in Patients With Advanced Solid Tumors
  • Official Title: An Open-label, Multi-center, Phase 1b/2 Study to Evaluate the Safety and Efficacy of Copanlisib in Combination With Nivolumab in Patients With Advanced Solid Tumors.

Clinical Trial IDs

  • ORG STUDY ID: 19769
  • NCT ID: NCT03735628

Conditions

  • Non-small Cell Lung Cancer (NSCLC), Head and Neck Squamous Cell Carcinoma (HNSCC), Colorectal Cancer (CRC), Hepatocellular Carcinoma (HCC)

Interventions

DrugSynonymsArms
CopanlisibDose escalation
NivolumabDose escalation

Purpose

The purpose of the dose escalation part of this study is to determine the feasibility of using the combination of copanlisib and nivolumab in subjects with advanced solid tumors, and to determine the maximum tolerated dose of copanlisib in combination with nivolumab. The maximum tolerated dose will then be used in Phase 2 (dose expansion) of the study.

Trial Arms

NameTypeDescriptionInterventions
Dose escalationExperimentalCopanlisib: 45 mg (dose level -1) or 60 mg (dose level 1) on Day 1, Day 8 and Day 15 (28 day cycle) Nivolumab: 240 mg on Day 15 of Cycle 1 and on Day 1 and Day 15 of subsequent cycles (28 day cycle).
  • Copanlisib
  • Nivolumab
Dose expansionExperimentalCopanlisib: Recommended phase 2 dose established in the phase 1b part on Day 1, Day 8 and Day 15 (28 day cycle) Nivolumab: 240 mg on Day 15 of Cycle 1 and on Day 1 and Day 15 of subsequent cycles (28 day cycle).
  • Copanlisib
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Participants with a histologically confirmed diagnosis of:

        Phase 1b:

          -  Advanced solid tumors where nivolumab is indicated as per the latest nivolumab
             Prescribing Information,

        Phase 2:

          -  Metastatic NSCLC, relapsed after prior platinum containing chemotherapy, irrespective
             of PD-L1 expression AND non-responding (no CR/PR) nonprogressing (no PD) on current
             nivolumab treatment. Patients with Epidermal growth factor receptor (EGFR) or
             Anaplastic lymphoma kinase (ALK) genomic tumor aberrations should have disease
             progression on FDA-approved therapy for these aberrations. Participants must have been
             on nivolumab therapy for at least 3 months prior to screening.

          -  Recurrent or metastatic HNSCC with disease progression on or after platinum-containing
             chemotherapy

          -  Microsatellite instability-high (MSI-H)/ Mismatch repair deficient) dMMR metastatic
             CRC that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and
             irinotecan

          -  HCC previously treated with Sorafenib

        Exclusion Criteria:

          -  Active, known or suspected autoimmune disease. Participants with vitiligo, type I
             diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring
             hormone replacement, psoriasis not requiring systemic treatment, or conditions not
             expected to recur in the absence of an external trigger are permitted to enroll.

          -  Major surgery, open biopsy or significant traumatic injury ≤ 28 days prior to first
             administration of study intervention. Central line surgery is not considered major
             surgery

          -  Symptomatic metastatic brain or meningeal carcinomatosis or tumors unless the
             participant is > 6 months from definitive therapy (surgery or radiotherapy), has no
             evidence of tumor growth on an imaging study and is clinically stable with respect to
             the tumor at the start of study intervention.

          -  Other malignancy within the last 5 years except for the following, which are
             permitted:

               -  curatively treated basal cell/squamous cell skin cancer,

               -  carcinoma in situ of the cervix,

               -  superficial transitional cell bladder carcinoma (if BCG [Bacillus
                  Calmette-Guerin] treatment was given, there should be a minimum of 6 months
                  between last dose and enrollment),

               -  in situ ductal carcinoma of the breast after complete resection,

               -  participants with localized, resected and/or low-risk prostate cancer may be
                  eligible after discussion with the sponsor's designated medical representative
                  and sponsor's approval.

          -  Other protocol inclusion/exclusion criteria may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1b: Frequency of dose limiting toxicities (DLT) at each dose level associated with administration of copanlisib and nivolumab
Time Frame:At the end of Cycle 2 of a 28-day cycle
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Phase 1b: Overall response rate (ORR) as per RECIST v 1.1 (by local investigator assessment)
Time Frame:Up to 26 months
Safety Issue:
Description:
Measure:Phase 1b and 2:Maximum drug concentration in plasma (Cmax) of copanlisib
Time Frame:At cycle1 day15, cycle2 day15, cycle 6 day15
Safety Issue:
Description:
Measure:Phase 1b and 2:Area under the curve (AUC) of copanlisib
Time Frame:At cycle1 day15, cycle2 day15,cycle 6 day15
Safety Issue:
Description:
Measure:Phase 1b and 2: Cmax for nivolumab
Time Frame:At cycle1 day15, cycle2 day15,cycle 6 day15
Safety Issue:
Description:
Measure:Phase 1b and 2: Minimum plasma drug concentration (Cmin) for nivolumab
Time Frame:At cycle1 day15, cycle2 day15,cycle 6 day15
Safety Issue:
Description:
Measure:Phase 1b and 2: Overall survival (OS)
Time Frame:Up to 26 months
Safety Issue:
Description:
Measure:Phase 1b and 2: Progression-free survival (PFS)
Time Frame:Up to 26 months
Safety Issue:
Description:
Measure:Phase 1b and 2: Disease control rate (DCR)
Time Frame:Up to 26 months
Safety Issue:
Description:
Measure:Phase 1b and 2: Duration of stable disease (DSD)
Time Frame:Up to 26 months
Safety Issue:
Description:
Measure:Phase 1b and 2: Time to response (TTR)
Time Frame:Up to 26 months
Safety Issue:
Description:
Measure:Phase 1b and 2: Time to progression (TTP)
Time Frame:Up to 26 months
Safety Issue:
Description:
Measure:Phase 1b and 2: Duration of response (DOR)
Time Frame:Up to 26 months
Safety Issue:
Description:
Measure:Phase 1b and 2:Number of participants with Adverse events (AE) and Serious AEs (SAE)
Time Frame:Up to 26 months
Safety Issue:
Description:
Measure:Phase 1b and 2:Number of participants with clinically significantly abnormal changes in electrocardiograms (ECG) including heart rate and measures PR, QRS, QT, and QTc intervals
Time Frame:Up to 26 months
Safety Issue:
Description:
Measure:Phase 1b and 2:Number of participants with changes in dose including interruptions, reductions and dose intensity
Time Frame:Up to 26 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Bayer

Last Updated