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.
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)
- Hepatocellular Carcinoma (HCC)
Interventions
Drug | Synonyms | Arms |
---|
Copanlisib | | Dose escalation |
Nivolumab | | Dose 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.
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Dose escalation | Experimental | 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). | |
Dose expansion | Experimental | 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). | |
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
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 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Bayer |
Last Updated
July 27, 2021