Clinical trial NCT03711058: Study of PI3Kinase Inhibition (Copanlisib) and Anti-PD-1 Antibody Nivolumab in Relapsed/Refractory Solid Tumors With Expansions in Mismatch-repair Proficient (MSS) Colorectal Cancer
Official title: A Phase I/II Study of PI3Kinase Inhibition (Copanlisib) and Anti-PD-1 Antibody Nivolumab in Relapsed/Refractory Solid Tumors With Expansions in Mismatch-repair Proficient (MSS) Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Unresectable or Metastatic Microsatellite Stable (MSS) Solid Tumor Along With Microsatellite Stable (MSS) Colon Cancer
Colon Cancer
Keywords: Immunotherapy
Nivolumab
Copanlisib
Unresectable
Metastatic
PD-1
P13K
Antibody
Solid Tumors
Colon Cancer
MSS
Mismatch-repair proficient
Microsatellite stable
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Bayer
name: Bristol-Myers Squibb
First posted: 2018-10-18
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: A phase I/II study of PI3Kinase inhibition (copanlisib) and anti-PD-1 antibody nivolumab in relapsed/refractory solid tumors with expansions in mismatch-repair proficient (MSS) colorectal cancer.


Eligibility criteria: Inclusion Criteria:

* Age ≥18 years.
* Ability to understand and willingness to sign a written informed consent document.
* Phase I: Must have received all curative treatment options and at least 2 lines of systemic therapy.
* Phase II: Must have received at least 2 lines of systemic therapy including a fluoropyrimidine, oxaliplatin, and irinotecan-containing regimen. KRAS/NRAS/BRAF wildtype patients must have received or refused anti-EGR.
* Must have received all curative treatment options and at least 2 lines of systemic and standard therapy.
* Must have measurable disease based on RECIST 1.1
* Must have biopsiable disease.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Life expectancy of greater than 3 months.
* Patients must have adequate organ and marrow function defined by study-specified laboratory tests within 21 days of initial study drug.
* Men must use acceptable form of birth control while on study.
* Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol.

Exclusion Criteria:

* Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti- PD-L2, anti-CTLA4, etc.).
* Prior therapy with a PI3K inhibitor
* Chemotherapy, target small molecule therapy, investigational therapy, or surgery within 4 weeks prior to first dose of treatment.
* Has received prior radiotherapy within 2 weeks prior to the start of treatment.
* Patient who is receiving or have received any other investigational agents within 4 weeks prior to the first dose of treatment.
* Has received a live vaccine 30 days prior to the first dose of study drug.
* Has known additional malignancy that is progressing or requires active treatment..
* Has known central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Has symptomatic ascites or has required a paracentesis in the last 12 weeks.
* Hypersensitivity reaction to study drug.
* Patients diagnosed of immunodeficiency or are on any immunosuppressive agents within 7 days prior to first dose of study drug.
* Has active autoimmune disease that has required systemic treatment in the past 12 months, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
* Has an active infection requiring systemic therapy.
* Infection with HIV or hepatitis B or C.
* Cytomegalovirus polymerase chain reaction (CMV PCR) positive.
* Known history or concurrent interstitial lung disease.
* Type I diabetes or Type II diabetes requiring treatment with a sulfonylurea, meglitinide, or insulin at screening.
* Uncontrolled cardiovascular disease.
* Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Use of anti-arrhythmic therapy (beta blockers or digoxin are permitted).
* Use of CYP3A4 inhibitors and inducers within 2 weeks of starting study drug and throughout treatment.
* Any arterial or venous thrombotic or embolic events within 3 months of start of study drug.
* Non-healing wound, ulcer, or fracture.
* Patients with evidence or history of bleeding condition.
* Had a blood or platelet transfusion within 7 days of Cycle 1 Day 1 treatment.
* Seizure disorder requiring anti-seizure medication.
* Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures.
* Are pregnant or breastfeeding.
* Unwilling or unable to follow the study schedule for any reason.

Primary outcomes:
measure: Number of Participants Experiencing a Dose Limiting Toxicity
timeFrame: 28 days
measure: 6-month Objective Response Rate (ORR) of Patients Treated With Copanlisib and Nivolumab
timeFrame: 6-months
Secondary outcomes:
measure: Disease Control Rate (DCR) Status at 6 Months.
timeFrame: 6-months
measure: Duration of Response (DOR)
timeFrame: 2 years
measure: Progression Free Survival (PFS)
timeFrame: 2 years
measure: Overall Survival (OS)
timeFrame: 2 years
measure: Number of Participants Experiencing Study Drug-related Toxicities
timeFrame: 2 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center
state: Maryland
Study officials:
affiliation: Johns Hopkins Medical Institution
name: Nilofer Azad, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Morschhauser F, Machiels JP, Salles G, Rottey S, Rule SAJ, Cunningham D, Peyrade F, Fruchart C, Arkenau HT, Genvresse I, Liu L, Kochert K, Shen K, Kneip C, Pena CE, Grevel J, Zhang J, Cisternas G, Reschke S, Granvil C, Awada A. On-Target Pharmacodynamic Activity of the PI3K Inhibitor Copanlisib in Paired Biopsies from Patients with Malignant Lymphoma and Advanced Solid Tumors. Mol Cancer Ther. 2020 Feb;19(2):468-478. doi: 10.1158/1535-7163.MCT-19-0466. Epub 2019 Oct 16.