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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

Completed Phase 1, PHASE2 Results posted Last updated 16 September 2025
What this trial tests

Phase 1, PHASE2 trial testing Copanlisib in Unresectable or Metastatic Microsatellite Stable (MSS) Solid Tumor in 48 participants. Completed in 30 June 2025.

Timeline
17 January 2019
Primary endpoint
14 June 2022
30 June 2025

Quick facts

Lead sponsorSidney Kimmel Comprehensive Cancer Center at Johns Hopkins
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment48
Start date17 January 2019
Primary completion14 June 2022
Estimated completion30 June 2025
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins — full company profile →

Who can join

18 and older, any sex, with Unresectable or Metastatic Microsatellite Stable (MSS) Solid Tumor or Microsatellite Stable (MSS) Colon Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Experiencing a Dose Limiting Toxicity Primary · 28 days

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 r

GroupValue95% CI
Phase I - Dose Finding (Dose Level 1)0
6-month Objective Response Rate (ORR) of Patients Treated With Copanlisib and Nivolumab Primary · 6-months

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.

GroupValue95% CI
Phase I - Dose Finding (Dose Level 1)0
Phase II /Cohort A- PI3K Mutation2
Phase II /Cohort B- PI3K Wild Type0
Disease Control Rate (DCR) Status at 6 Months. Secondary · 6-months

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.

GroupValue95% CI
Phase I - Dose Finding0
Phase II /Cohort A - PI3K Mutation5
Phase II /Cohort B - PI3K Wild Type3
Duration of Response (DOR) Secondary · 3 years

Number of months from the first documentation of a partial or complete response by RECIST 1.1 to date of disease progression. Responses may be documented at any time on the study, including patients responding after the 6-month evaluation used for the primary outcome.

GroupValue95% CI
Phase II /Cohort A- PI3K Mutation20.617.0 – 22.8
Phase II /Cohort B- PI3K Wild Type13.113.1 – 13.1
Progression Free Survival (PFS) Secondary · 3 years

Number of months from treatment to disease progression (PD)

GroupValue95% CI
Phase I - Dose Finding (Dose Level 1)1.641.38 – NA
Phase II /Cohort A- PI3K Mutation1.681.64 – NA
Phase II /Cohort B- PI3K Wild Type1.821.68 – NA
Overall Survival (OS) Secondary · 3 years

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

GroupValue95% CI
Phase I - Dose Finding (Dose Level 1)5.612.4 – NA
Phase II /Cohort A- PI3K Mutation6.774.21 – 16.04
Phase II /Cohort B- PI3K Wild Type10.264.8 – NA
Number of Participants Experiencing Study Drug-related Toxicities Secondary · 51 months

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

GroupValue95% CI
Phase I - Dose Finding (Dose Level 1)5
Phase II /Cohort A- PI3K Mutation16
Phase II /Cohort B- PI3K Wild Type10

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 51 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase I - Dose Finding (Dose Level 1)
Serious: 3/6 (50%)
Deaths: 6/6
Phase II /Cohort A - PI3K Mutation
Serious: 11/21 (52%)
Deaths: 14/21
Phase II /Cohort B - PI3K Wild Type
Serious: 6/12 (50%)
Deaths: 9/12

Serious adverse events (26 terms)

ReactionSystemPhase I - Dose Finding (Do…Phase II /Cohort A - PI3K …Phase II /Cohort B - PI3K …
Disease progressionGeneral disorders
ColitisGastrointestinal disorders
Abdominal painGastrointestinal disorders
FeverGeneral disorders
Chylous ascitesGastrointestinal disorders
Colonic obstructionGastrointestinal disorders
Colonic perforationGastrointestinal disorders
DiarrheaGastrointestinal disorders
NauseaGastrointestinal disorders
Upper gastrointestinal hemorrhageGastrointestinal disorders
VomitingGastrointestinal disorders
Hepatic failureHepatobiliary disorders
Hip fractureInjury, poisoning and procedural complications
HyperglycemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
ChylothoraxRespiratory, thoracic and mediastinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Rash maculopapularSkin and subcutaneous tissue disorders
Thromboembolic eventVascular disorders
Oral MucositisGastrointestinal disorders
Vocal Cord ParalysisRespiratory, thoracic and mediastinal disorders
SepsisInfections and infestations
Respiratory FailureRespiratory, thoracic and mediastinal disorders
Other adverse events (114 terms — click to expand)

ReactionSystemPhase I - Dose Finding (Do…Phase II /Cohort A - PI3K …Phase II /Cohort B - PI3K …
NauseaGastrointestinal disorders
FatigueGeneral disorders
VomitingGastrointestinal disorders
HypertensionVascular disorders
Weight lossInvestigations
Rash maculopapularSkin and subcutaneous tissue disorders
HyperglycemiaMetabolism and nutrition disorders
DiarrheaGastrointestinal disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
ALT increasedInvestigations
PruritusSkin and subcutaneous tissue disorders
AnemiaBlood and lymphatic system disorders
Alkaline phosphatase increasedInvestigations
Lipase increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Oral MucositisGastrointestinal disorders
Edema limbsGeneral disorders
Infusion related reactionInjury, poisoning and procedural complications
AST increasedInvestigations
Serum amylase increasedInvestigations
AnorexiaMetabolism and nutrition disorders
DehydrationMetabolism and nutrition disorders
HeadacheNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
HyperthyroidismEndocrine disorders
HypothyroidismEndocrine disorders
AscitesGastrointestinal disorders
BelchingGastrointestinal disorders
BloatingGastrointestinal disorders
ColitisGastrointestinal disorders
Dry mouthGastrointestinal disorders
FlatulenceGastrointestinal disorders
Lip painGastrointestinal disorders
ChillsGeneral disorders
FeverGeneral disorders
ThrushInfections and infestations
Blood bilirubin increasedInvestigations
HypomagnesemiaMetabolism and nutrition disorders

Most-reported serious reactions: Disease progression, Colitis, Abdominal pain, Fever, Chylous ascites, Colonic obstruction, Colonic perforation, Diarrhea.

Data from ClinicalTrials.gov NCT03711058 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Tumor-Associated Macrophages Regulate PD-1/PD-L1 Immunosuppression.
    Pu Y, Ji Q. · · 2022 · cited 212× · PMID 35592338 · DOI 10.3389/fimmu.2022.874589
  2. Emerging role of PTEN loss in evasion of the immune response to tumours.
    Vidotto T, Melo CM, Castelli E, Koti M, et al · · 2020 · cited 163× · PMID 32327707 · DOI 10.1038/s41416-020-0834-6
  3. Immunotherapy efficacy on mismatch repair-deficient colorectal cancer: From bench to bedside.
    Lizardo DY, Kuang C, Hao S, Yu J, et al · · 2020 · cited 160× · PMID 33035640 · DOI 10.1016/j.bbcan.2020.188447
  4. PI3K/Akt/mTOR Signaling Pathway as a Target for Colorectal Cancer Treatment.
    Leiphrakpam PD, Are C. · · 2024 · cited 105× · PMID 38542151 · DOI 10.3390/ijms25063178
  5. Defects in Macrophage Reprogramming in Cancer Therapy: The Negative Impact of PD-L1/PD-1.
    Cai H, Zhang Y, Wang J, Gu J. · · 2021 · cited 100× · PMID 34248982 · DOI 10.3389/fimmu.2021.690869
  6. Harnessing the immune system against cancer: current immunotherapy approaches and therapeutic targets.
    Kumar AR, Devan AR, Nair B, Vinod BS, et al · · 2021 · cited 98× · PMID 34671902 · DOI 10.1007/s11033-021-06752-9
  7. Neutrophils in the era of immune checkpoint blockade.
    Faget J, Peters S, Quantin X, Meylan E, et al · · 2021 · cited 94× · PMID 34301813 · DOI 10.1136/jitc-2020-002242
  8. PD-1 and PD-L1 inhibitors in cold colorectal cancer: challenges and strategies.
    Lin KX, Istl AC, Quan D, Skaro A, et al · · 2023 · cited 90× · PMID 37831146 · DOI 10.1007/s00262-023-03520-5

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