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

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ClinicalTrials.gov Identifier: NCT03735628
Recruitment Status : Not yet recruiting
First Posted : November 8, 2018
Last Update Posted : November 8, 2018
Sponsor:
Information provided by (Responsible Party):
Bayer

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer (NSCLC), Head and Neck Squamous Cell Carcinoma (HNSCC), Colorectal Cancer (CRC), Hepatocellular Carcinoma (HCC) Drug: Copanlisib Drug: Nivolumab Phase 1 Phase 2

Study Type : Interventional
Estimated Enrollment : 160 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Estimated Study Start Date : October 31, 2018
Estimated Primary Completion Date : April 30, 2021
Estimated Study Completion Date : April 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dose escalation

Copanlisib:

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).

Drug: Copanlisib
Copanlisib: lyophilisate for reconstitution and further dilution for infusion

Drug: Nivolumab
Nivolumab: concentrate for solution for infusion

Experimental: Dose expansion

Copanlisib:

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).

Drug: Copanlisib
Copanlisib: lyophilisate for reconstitution and further dilution for infusion

Drug: Nivolumab
Nivolumab: concentrate for solution for infusion




Primary Outcome Measures :
  1. 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 ]
  2. Phase 2: Overall response rate (ORR) as per RECIST v 1.1 (Response evaluation criteria in solid tumors, v 1.1) (by local investigator [ Time Frame: Up to 26 months ]

Secondary Outcome Measures :
  1. Phase 1b: Overall response rate (ORR) as per RECIST v 1.1 (by local investigator assessment) [ Time Frame: Up to 26 months ]
  2. Phase 1b and 2:Maximum drug concentration in plasma (Cmax) of copanlisib [ Time Frame: At cycle1 day15, cycle2 day15, cycle 6 day15 ]
  3. Phase 1b and 2:Area under the curve (AUC) of copanlisib [ Time Frame: At cycle1 day15, cycle2 day15,cycle 6 day15 ]
  4. Phase 1b and 2: Cmax for nivolumab [ Time Frame: At cycle1 day15, cycle2 day15,cycle 6 day15 ]
  5. Phase 1b and 2: Minimum plasma drug concentration (Cmin) for nivolumab [ Time Frame: At cycle1 day15, cycle2 day15,cycle 6 day15 ]
  6. Phase 1b and 2: Overall survival (OS) [ Time Frame: Up to 26 months ]
  7. Phase 1b and 2: Progression-free survival (PFS) [ Time Frame: Up to 26 months ]
  8. Phase 1b and 2: Disease control rate (DCR) [ Time Frame: Up to 26 months ]
  9. Phase 1b and 2: Duration of stable disease (DSD) [ Time Frame: Up to 26 months ]
  10. Phase 1b and 2: Time to response (TTR) [ Time Frame: Up to 26 months ]
  11. Phase 1b and 2: Time to progression (TTP) [ Time Frame: Up to 26 months ]
  12. Phase 1b and 2: Duration of response (DOR) [ Time Frame: Up to 26 months ]
  13. Phase 1b and 2:Number of participants with Adverse events (AE) and Serious AEs (SAE) [ Time Frame: Up to 26 months ]
  14. 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 ]
  15. Phase 1b and 2:Number of participants with changes in dose including interruptions, reductions and dose intensity [ Time Frame: Up to 26 months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03735628


Contacts
Contact: Bayer Clinical Trials Contact (+)1-888-84 22937 clinical-trials-contact@bayer.com
Contact: For trial location information (Phone Menu Options '3' or '4') (+)1-888-84 22937

Sponsors and Collaborators
Bayer

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT03735628     History of Changes
Other Study ID Numbers: 19769
First Posted: November 8, 2018    Key Record Dates
Last Update Posted: November 8, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Carcinoma, Squamous Cell
Carcinoma, Hepatocellular
Head and Neck Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Adenocarcinoma
Liver Neoplasms
Liver Diseases
Nivolumab