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

Non-small Cell Lung Cancer (NSCLC) Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT03735628
• Other study ID #: 19769
• Status: Completed
• Phase: Phase 1
• Start date: October 17, 2018
• Est. completion date: October 13, 2022

Study information

• Verified date: October 2023
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: October 13, 2022
• Est. primary completion date: October 13, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Copanlisib
Copanlisib: lyophilisate for reconstitution and further dilution for infusion
• Nivolumab
Nivolumab: concentrate for solution for infusion

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
United States	Tower Hematology/Oncology Medical Group	Beverly Hills	California
United States	Gabrail Cancer Center	Canton	Ohio
United States	Rocky Mountain Cancer Centers / Denver, CO	Denver	Colorado
United States	Orthopaedic Institute for Children	Los Angeles	California
United States	Rhode Island Hospital	Providence	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1b: Frequency of dose limiting toxicities (DLT) at each dose level associated with administration of copanlisib and nivolumab		At the end of Cycle 2 of a 28-day cycle
Primary	Phase 2: Overall response rate (ORR) as per RECIST v 1.1 (Response evaluation criteria in solid tumors, v 1.1) (by local investigator		Up to 26 months
Secondary	Phase 1b: Overall response rate (ORR) as per RECIST v 1.1 (by local investigator assessment)		Up to 26 months
Secondary	Phase 1b and 2:Maximum drug concentration in plasma (Cmax) of copanlisib		At cycle1 day15, cycle2 day15, cycle 6 day15
Secondary	Phase 1b and 2:Area under the curve (AUC) of copanlisib		At cycle1 day15, cycle2 day15,cycle 6 day15
Secondary	Phase 1b and 2: Cmax for nivolumab		At cycle1 day15, cycle2 day15,cycle 6 day15
Secondary	Phase 1b and 2: Minimum plasma drug concentration (Cmin) for nivolumab		At cycle1 day15, cycle2 day15,cycle 6 day15
Secondary	Phase 1b and 2: Overall survival (OS)		Up to 26 months
Secondary	Phase 1b and 2: Progression-free survival (PFS)		Up to 26 months
Secondary	Phase 1b and 2: Disease control rate (DCR)		Up to 26 months
Secondary	Phase 1b and 2: Duration of stable disease (DSD)		Up to 26 months
Secondary	Phase 1b and 2: Time to response (TTR)		Up to 26 months
Secondary	Phase 1b and 2: Time to progression (TTP)		Up to 26 months
Secondary	Phase 1b and 2: Duration of response (DOR)		Up to 26 months
Secondary	Phase 1b and 2:Number of participants with Adverse events (AE) and Serious AEs (SAE)		Up to 26 months
Secondary	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		Up to 26 months
Secondary	Phase 1b and 2:Number of participants with changes in dose including interruptions, reductions and dose intensity		Up to 26 months

External Links

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