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

Primary Purpose

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

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Copanlisib

Nivolumab

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer (NSCLC)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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, progressing on or after prior pembrolizumab therapy with or without chemotherapy, irrespective of PD-L1 expression Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations.
Recurrent or metastatic HNSCC progressing on or after prior pembrolizumab therapy with or without chemotherapy
HCC progressing after any prior therapy.

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

Sites / Locations

Tower Hematology/Oncology Medical Group
Orthopaedic Institute for Children
Rocky Mountain Cancer Centers / Denver, CO
Gabrail Cancer Center
Rhode Island Hospital
Princess Margaret Cancer Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Dose escalation

Dose expansion

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

Phase 1b: Frequency of dose limiting toxicities (DLT) at each dose level associated with administration of copanlisib and nivolumab

Phase 2: Overall response rate (ORR) as per RECIST v 1.1 (Response evaluation criteria in solid tumors, v 1.1) (by local investigator

Secondary Outcome Measures

Phase 1b: Overall response rate (ORR) as per RECIST v 1.1 (by local investigator assessment)

Phase 1b and 2:Maximum drug concentration in plasma (Cmax) of copanlisib

Phase 1b and 2:Area under the curve (AUC) of copanlisib

Phase 1b and 2: Cmax for nivolumab

Phase 1b and 2: Minimum plasma drug concentration (Cmin) for nivolumab

Phase 1b and 2: Overall survival (OS)

Phase 1b and 2: Progression-free survival (PFS)

Phase 1b and 2: Disease control rate (DCR)

Phase 1b and 2: Duration of stable disease (DSD)

Phase 1b and 2: Time to response (TTR)

Phase 1b and 2: Time to progression (TTP)

Phase 1b and 2: Duration of response (DOR)

Phase 1b and 2:Number of participants with Adverse events (AE) and Serious AEs (SAE)

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

Phase 1b and 2:Number of participants with changes in dose including interruptions, reductions and dose intensity

Full Information

NCT ID

NCT03735628

First Posted

October 25, 2018

Last Updated

October 4, 2023

Sponsor

Bayer

1. Study Identification

Unique Protocol Identification Number

NCT03735628

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.

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Completed

Study Start Date

October 17, 2018 (Actual)

Primary Completion Date

October 13, 2022 (Actual)

Study Completion Date

October 13, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bayer

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

Detailed Description

Study was originally designed with both Phase I and Phase II part, but sponsor decided not to conduct Phase 2 part due to strategic portfolio re-prioritization.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose escalation

Arm Type

Experimental

Arm Description

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).

Arm Title

Dose expansion

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Copanlisib

Intervention Description

Copanlisib: lyophilisate for reconstitution and further dilution for infusion

Intervention Type

Drug

Intervention Name(s)

Nivolumab

Intervention Description

Nivolumab: concentrate for solution for infusion

Primary Outcome Measure Information:

Title

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

Title

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 Measure Information:

Title

Phase 1b: Overall response rate (ORR) as per RECIST v 1.1 (by local investigator assessment)

Time Frame

Up to 26 months

Title

Phase 1b and 2:Maximum drug concentration in plasma (Cmax) of copanlisib

Time Frame

At cycle1 day15, cycle2 day15, cycle 6 day15

Title

Phase 1b and 2:Area under the curve (AUC) of copanlisib

Time Frame

At cycle1 day15, cycle2 day15,cycle 6 day15

Title

Phase 1b and 2: Cmax for nivolumab

Time Frame

At cycle1 day15, cycle2 day15,cycle 6 day15

Title

Phase 1b and 2: Minimum plasma drug concentration (Cmin) for nivolumab

Time Frame

At cycle1 day15, cycle2 day15,cycle 6 day15

Title

Phase 1b and 2: Overall survival (OS)

Time Frame

Up to 26 months

Title

Phase 1b and 2: Progression-free survival (PFS)

Time Frame

Up to 26 months

Title

Phase 1b and 2: Disease control rate (DCR)

Time Frame

Up to 26 months

Title

Phase 1b and 2: Duration of stable disease (DSD)

Time Frame

Up to 26 months

Title

Phase 1b and 2: Time to response (TTR)

Time Frame

Up to 26 months

Title

Phase 1b and 2: Time to progression (TTP)

Time Frame

Up to 26 months

Title

Phase 1b and 2: Duration of response (DOR)

Time Frame

Up to 26 months

Title

Phase 1b and 2:Number of participants with Adverse events (AE) and Serious AEs (SAE)

Time Frame

Up to 26 months

Title

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

Title

Phase 1b and 2:Number of participants with changes in dose including interruptions, reductions and dose intensity

Time Frame

Up to 26 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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, progressing on or after prior pembrolizumab therapy with or without chemotherapy, irrespective of PD-L1 expression Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations. Recurrent or metastatic HNSCC progressing on or after prior pembrolizumab therapy with or without chemotherapy HCC progressing after any prior therapy. 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

Facility Information:

Facility Name

Tower Hematology/Oncology Medical Group

City

Beverly Hills

State/Province

California

ZIP/Postal Code

90211-1850

Country

United States

Facility Name

Orthopaedic Institute for Children

City

Los Angeles

State/Province

California

ZIP/Postal Code

90001

Country

United States

Facility Name

Rocky Mountain Cancer Centers / Denver, CO

City

Denver

State/Province

Colorado

ZIP/Postal Code

80218

Country

United States

Facility Name

Gabrail Cancer Center

City

Canton

State/Province

Ohio

ZIP/Postal Code

44718

Country

United States

Facility Name

Rhode Island Hospital

City

Providence

State/Province

Rhode Island

ZIP/Postal Code

20903

Country

United States

Facility Name

Princess Margaret Cancer Centre

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 1Z5

Country

Canada

12. IPD Sharing Statement

Links:

URL

http://clinicaltrials.bayer.com/

Description

Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

Learn more about this trial

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

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