Neoplasms

Digestive System Diseases

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Colonic Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

All Drugs and Chemicals

Antineoplastic Agents

Herbal and Botanical

Antibodies

Immunomodulating Agents

Nivolumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Cola

Copanlisib will be administered as a 60 minute IV infusion (-5min/+10min) at a dose of 45 mg - 60 mg IV. Copanlisib will be administered once a week (days 1, 8, and 15 or Day 1 and Day 15 of each 28 day cycle).

Drug: 45 or 60 mg IV

Copanlisib

Nivolumab 480 mg will be administered as a 30 minute IV infusion (-5min/+10min) on Day 1 of each 28 day cycle.

Drug: 480 mg IV

Nilofer Azad, MD

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 of PI3Kinase Inhibition (Copanlisib) and Anti-PD-1 Antibody Nivolumab in Relapsed/Refractory Solid Tumors With Expansions in Mismatch-repair Proficient (MSS) Colorectal Cancer

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

Number of participants experiencing a Dose Limiting Toxicity (DLT) in each dose level. DLT is defined as any of the following study drug-related toxicities occurring during the first cycle of study drug on study:

* Grade 4 anemia
* Grade ≥ 3 neutropenia lasting ≥ 14 days
* Grade ≥ 3 febrile neutropenia
* Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with clinically significant bleeding
* Treatment-related ≥ grade 4 AEs, except transient hyperglycemia
* Grade ≥ 3 Pneumonitis or recurrent Grade 2 pneumonitis
* Grade ≥ 3 Nephritis
* Grade ≥ 3 elevated AST or ALT
* Grade ≥ 2 eye pain or reduction of visual acuity that does not respond to topical therapy, improve to ≤ grade 1 within 2 weeks of topical therapy, or requires systemic therapy
* Any other Grade ≥ 3 toxicities (with certain exceptions for transient AEs or asymptomatic labs)

The proportion of subjects with partial response (PR) or complete response (CR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Per RECIST 1.1, complete response is defined as disappearance of all target lesions, and partial response is defined as at least a 30% decrease in the sum of diameters of target lesions. Lesions are assessed by CT or MRI.

Percentage of participants achieving stable disease (SD) or better (SD + PR + CR).

Per RECIST 1.1, complete response is defined as disappearance of all target lesions, partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, stable disease occurs when there is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least 20% increase). Lesions are assessed by CT or MRI.

Number of months from the first documentation of a response to date of disease progression.

Number of months from treatment to disease progression (PD)

Number of months from the date of first treatment until death or end of follow-up.

Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0.

Bayer

Bristol-Myers Squibb

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements.

Copanlisib will be administered as a 60-minute IV infusion (-5min/+10min) at Dose Level 1: 60mg on Day 1, 8, and 15 of each 28-day cycle.

Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.

Phase I - Dose Finding (Dose Level 1)

Copanlisib 60 mg will be administered as a 60-minute IV infusion (-5min/+10min) on Day 1, 8, and 15 of each 28-day cycle.

Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each 28-day cycle.

Phase II /Cohort A - PI3K Mutation

Phase II /Cohort B - PI3K Wild Type

Copanlisib: Copanlisib will be administered as a 60 minute IV infusion (-5min/+10min) at one of three dose levels:

Dose Level 1: 60mg on Day 1, 8, and 15

Dose Level -1: 60mg on Day 1 and 15

Dose Level -2: 45 mg on Day 1 and 15

Nivolumab: Nivolumab 480 mg will be administered as a 30 minute IV infusion (-5min/+10min) on Day 1 of each cycle.

Cycle length is 28 days.

Only Dose Level 1 was tested.

Phase I - Dose Finding

Phase II/Cohort B - PI3K Wild Type

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Measure description: The ECOG scale measures performance status , which scores ranging from 0-5: 0=fully active , performs without restrictions, 1=can ambulate,but restricted in physical strenuous activity,2=ambulatory and capable of self care , but unable to work , active for \>50%of waking hours,3=limited self care, confined to bed or chair for \>50%of waking hours,4=completely disabled, totally confined tp bed/chair,5= deceased

Eastern Cooperative Oncology Group (ECOG) Classification of Participants

Per protocol, Dose Limiting Toxicities (DLTs) were only assessed in Phase I subjects in order to determine the Phase II dose of copanlisib. Since no subjects experienced DLTs in Dose Level 1, this was the only dose level tested.

Number of Participants Experiencing a Dose Limiting Toxicity

Phase II /Cohort A- PI3K Mutation

Phase II /Cohort B- PI3K Wild Type

6-month Objective Response Rate (ORR) of Patients Treated With Copanlisib and Nivolumab

Copanlisib will be administered as a 60-minute IV infusion (-5min/+10min) at one of three dose levels:

Dose Level 1: 60mg on Day 1, 8, and 15

Dose Level -1: 60mg on Day 1 and 15

Dose Level -2: 45 mg on Day 1 and 15

Nivolumab 480 mg will be administered as a 30-minute IV infusion (-5min/+10min) on Day 1 of each cycle.

Cycle length is 28 days.

Only Dose Level 1 was tested.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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	NCT03711058	Unresectable or... Colon Cancer	Copanlisib Nivolumab	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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	NCT03711058	Unresectable or... Colon Cancer	Copanlisib Nivolumab	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Spots Global Cancer Trial Database for unresectable or metastatic microsatellite stable (mss) solid tumor along with microsatellite stable (mss) colon cancer