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

NCT03735628 | Completed Phase 1 FDA Drug

• 1 other identifier: 19769
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 6

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (15)

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

  Up to 26 months

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

  At cycle1 day15, cycle2 day15, cycle 6 day15

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

  At cycle1 day15, cycle2 day15,cycle 6 day15

• Phase 1b and 2: Cmax for nivolumab

  At cycle1 day15, cycle2 day15,cycle 6 day15

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

  At cycle1 day15, cycle2 day15,cycle 6 day15

Study Arms (2)

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).

Drug: Copanlisib; Drug: Nivolumab

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).

Drug: Copanlisib; Drug: Nivolumab

Interventions

Copanlisib DRUG

Copanlisib: lyophilisate for reconstitution and further dilution for infusion

Dose escalation; Dose expansion

Nivolumab DRUG

Nivolumab: concentrate for solution for infusion

Dose escalation; Dose expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bayer: lead

Study Sites (6)

Tower Hematology/Oncology Medical Group

Beverly Hills, California, 90211-1850, United States

Location

Orthopaedic Institute for Children

Los Angeles, California, 90001, United States

Location

Rocky Mountain Cancer Centers / Denver, CO

Denver, Colorado, 80218, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 20903, United States

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 1Z5, Canada

Location

Related Links

• 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.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Hepatocellular

Interventions

copanlisib; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2018
• First Posted: November 8, 2018
• Study Start: October 17, 2018
• Primary Completion: October 13, 2022
• Study Completion: October 13, 2022
• Last Updated: October 6, 2023

Record last verified: 2023-10

Locations

US (5); CA (1)