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NCT03651271

Nivolumab With or Without Ipilimumab in Advanced Metastatic Cancer

Completed Phase 2 Results posted Last updated 7 February 2024
What this trial tests

Phase 2 trial testing Nivolumab Monotherapy in Advanced Metastatic Cancer in 100 participants. Completed in 30 June 2023.

Timeline
17 October 2018
Primary endpoint
30 June 2023
30 June 2023

Quick facts

Lead sponsorParker Institute for Cancer Immunotherapy
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment100
Start date17 October 2018
Primary completion30 June 2023
Estimated completion30 June 2023
Sites6 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Parker Institute for Cancer Immunotherapy

Who can join

18 and older, any sex, with Advanced Metastatic Cancer or Advanced Prostate 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.

Clinical Benefit Rate (CBR) of Nivolumab With or Without Ipilimumab Primary · Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy, whichever occurred first, up to 43 months

CBR is defined as the percentage of participants who show clinical benefit, defined as obtaining a complete response (CR; disappearance of all target and non-target lesions), partial response (PR; ≥ 30% decrease in the sum of the longest diameter of target lesions), or stable disease (SD) for ≥ 6 months, as determined by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1.

GroupValue95% CI
"Hot" Tumors for Advanced Metastatic Cancer1
"Cold" Tumors for Advanced Metastatic Cancer18
"Hot" Tumors for Advanced Prostate Cancer1
"Cold" Tumors for Advanced Prostate Cancer Cohort A1
"Cold" Tumors for Advanced Prostate Cancer Cohort B3
Percentage of Participants Whose Tumors Convert From CD8 Low (<15% Tumoral CD8) to CD8 High (>=15%). Primary · From initiation of study intervention through the 2nd on-treatment tumor biopsy, up to 8 months

Percentage of participants in the nivolumab plus ipilimumab ("CD8 low") arm whose tumors convert from CD8 low (\<15%) to CD8 high (\>=15%) as measured by the percentage of tumoral CD8 cells. Participants in the CD8 high arms are not evaluated for this outcome. On-treatment biopsies for the advanced metastatic cancer cohort were scheduled for as early as possible after the 2nd and 4th doses of ipilimumab (Day 2 - 10 of Cycle 2 and Cycle 6, respectively). On-treatment biopsies for the advanced prostate cancer cohort were scheduled for within 3 days (+/-) of the 2nd and 4th doses of nivolumab (D

GroupValue95% CI
"Cold" Tumors for Advanced Metastatic Cancer14
"Cold" Tumors for Advanced Prostate Cancer Cohort A1
"Cold" Tumors for Advanced Prostate Cancer Cohort B1
Number of Participants With Treatment-related Adverse Events (TRAE) Secondary · From signing informed consent (prior to Screening) through 100 days after last dose, up to 43 months.

Investigators recorded adverse events (AEs) during each participant encounter. AE severity was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, which grades AEs on a 1 to 5 scale: Grades 1 and 2 indicate mild to moderate events; Grade 3 denotes severe events; Grades 4 and 5 signify life-threatening or fatal outcomes. A TRAE is defined as any event that either occurs after the initiation of study intervention, having been absent at baseline, or, if present at baseline, appears to have worsened in severity or frequency, that is deemed 'Possibly', 'Probably'

Any Treatment-related adverse event (TRAE)
GroupValue95% CI
"Hot" Tumors for Advanced Metastatic Cancer4
"Cold" Tumors for Advanced Metastatic Cancer58
"Hot" Tumors for Advanced Prostate Cancer1
"Cold" Tumors for Advanced Prostate Cancer Cohort A4
"Cold" Tumors for Advanced Prostate Cancer Cohort B12
Grade 3 or Grade 4 TRAE
GroupValue95% CI
"Hot" Tumors for Advanced Metastatic Cancer0
"Cold" Tumors for Advanced Metastatic Cancer20
"Hot" Tumors for Advanced Prostate Cancer0
"Cold" Tumors for Advanced Prostate Cancer Cohort A2
"Cold" Tumors for Advanced Prostate Cancer Cohort B6
Grade 5 TRAE
GroupValue95% CI
"Hot" Tumors for Advanced Metastatic Cancer0
"Cold" Tumors for Advanced Metastatic Cancer0
"Hot" Tumors for Advanced Prostate Cancer0
"Cold" Tumors for Advanced Prostate Cancer Cohort A0
"Cold" Tumors for Advanced Prostate Cancer Cohort B0
Serious TRAE
GroupValue95% CI
"Hot" Tumors for Advanced Metastatic Cancer0
"Cold" Tumors for Advanced Metastatic Cancer10
"Hot" Tumors for Advanced Prostate Cancer0
"Cold" Tumors for Advanced Prostate Cancer Cohort A1
"Cold" Tumors for Advanced Prostate Cancer Cohort B6
TRAE leading to treatment discontinuation
GroupValue95% CI
"Hot" Tumors for Advanced Metastatic Cancer0
"Cold" Tumors for Advanced Metastatic Cancer4
"Hot" Tumors for Advanced Prostate Cancer0
"Cold" Tumors for Advanced Prostate Cancer Cohort A0
"Cold" Tumors for Advanced Prostate Cancer Cohort B5
Objective Response Rate (ORR) Secondary · Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy, whichever occurred first, up to 43 months

Objective Response Rate (ORR) is defined as the percentage of participants who attain a best overall response of complete response (CR; disappearance of all target and non-target lesions) or partial response (PR; \>= 30% decrease in the sum of the longest diameter of target lesions), as determined by Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.

GroupValue95% CI
"Hot" Tumors for Advanced Metastatic Cancer1
"Cold" Tumors for Advanced Metastatic Cancer14
"Hot" Tumors for Advanced Prostate Cancer0
"Cold" Tumors for Advanced Prostate Cancer Cohort A0
"Cold" Tumors for Advanced Prostate Cancer Cohort B1
Progression-free Survival (PFS) Secondary · Initiation of study drug through death, radiographic progression or initiation of new anti-cancer therapy, whichever occurred first, up to 43 months

PFS is defined as the time from initiation of study intervention to the date of first documented radiographic progression of disease or date of death due to any cause, whichever occurred first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

GroupValue95% CI
"Hot" Tumors for Advanced Metastatic Cancer2.01.1 – NA
"Cold" Tumors for Advanced Metastatic Cancer2.32.0 – 4.3
"Hot" Tumors for Advanced Prostate CancerNANA – NA
"Cold" Tumors for Advanced Prostate Cancer Cohort A3.71.1 – NA
"Cold" Tumors for Advanced Prostate Cancer Cohort B5.72.0 – 7.9
Overall Survival (OS) Secondary · From initiation of study drug until death due to any cause, up to 43 months

OS is defined as the time from initiation of study intervention until death due to any cause. Participants not reported as having died at the time of analysis were censored at the most recent contact date they were known to be alive.

GroupValue95% CI
"Hot" Tumors for Advanced Metastatic Cancer15.812.1 – NA
"Cold" Tumors for Advanced Metastatic Cancer13.98.9 – 21.1
"Hot" Tumors for Advanced Prostate CancerNANA – NA
"Cold" Tumors for Advanced Prostate Cancer Cohort ANA1.1 – NA
"Cold" Tumors for Advanced Prostate Cancer Cohort BNA4.9 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: From initiation of study drug until death due to any cause, up to 43 months. All adverse events (AEs), regardless of relationship to study drug, were collected from the time the participant signed informed consent until 100 days after the last dose of study intervention. Serious Adverse Events (SAEs) that occurred after the end of the AE reporting period (100-days post last dose) and that were considered to be reasonably related to the study drug by the investigator, were also collected.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

"Hot" Tumors for Advanced Metastatic Cancer
Serious: 2/7 (29%)
Deaths: 4/7
"Cold" Tumors for Advanced Metastatic Cancer
Serious: 30/72 (42%)
Deaths: 39/72
"Hot" Tumors for Advanced Prostate Cancer
Serious: 0/1 (0%)
Deaths: 0/1
"Cold" Tumors for Advanced Prostate Cancer Cohort A
Serious: 2/5 (40%)
Deaths: 2/5
"Cold" Tumors for Advanced Prostate Cancer Cohort B
Serious: 8/15 (53%)
Deaths: 6/15

Serious adverse events (58 terms)

ReactionSystem"Hot" Tumors for Advanced …"Cold" Tumors for Advanced…"Hot" Tumors for Advanced …"Cold" Tumors for Advanced…"Cold" Tumors for Advanced…
PneumoniaInfections and infestations
Immune-Mediated EnterocolitisGastrointestinal disorders
ThyroiditisEndocrine disorders
PyrexiaGeneral disorders
SepsisInfections and infestations
Confusional statePsychiatric disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HypotensionVascular disorders
Cardio-respiratory arrestCardiac disorders
Myocardial infarctionCardiac disorders
HypophysitisEndocrine disorders
Retinal vascular disorderEye disorders
Vision blurredEye disorders
Anal incontinenceGastrointestinal disorders
ColitisGastrointestinal disorders
ConstipationGastrointestinal disorders
GastritisGastrointestinal disorders
OesophagitisGastrointestinal disorders
VomitingGastrointestinal disorders
FatigueGeneral disorders
Influenza like illnessGeneral disorders
CholecystitisHepatobiliary disorders
HypertransaminasaemiaHepatobiliary disorders
HypersensitivityImmune system disorders
PeritonitisInfections and infestations
Other adverse events (131 terms — click to expand)

ReactionSystem"Hot" Tumors for Advanced …"Cold" Tumors for Advanced…"Hot" Tumors for Advanced …"Cold" Tumors for Advanced…"Cold" Tumors for Advanced…
FatigueGeneral disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
RashSkin and subcutaneous tissue disorders
AnaemiaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
VomitingGastrointestinal disorders
Decreased AppetiteMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
Abdominal PainGastrointestinal disorders
MyalgiaMusculoskeletal and connective tissue disorders
PruritusSkin and subcutaneous tissue disorders
Lipase increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
Blood Creatinine IncreasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
Aspartate Aminotransferase IncreasedInvestigations
HyponatraemiaMetabolism and nutrition disorders
HypothyroidismEndocrine disorders
DehydrationMetabolism and nutrition disorders
PyrexiaGeneral disorders
InsomniaPsychiatric disorders
HypertensionVascular disorders
Alanine Aminotransferase IncreasedInvestigations
StomatitisGastrointestinal disorders
ChillsGeneral disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
DizzinessNervous system disorders
Lymphocyte count decreasedInvestigations
Weight DecreasedInvestigations
Blood bilirubin increasedInvestigations
Blood Thyroid Stimulating Hormone IncreasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
Influenza like illnessGeneral disorders
Oedema peripheralGeneral disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
Pain In ExtremityMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Pneumonia, Immune-Mediated Enterocolitis, Thyroiditis, Pyrexia, Sepsis, Confusional state, Dyspnoea, Hypotension.

Data from ClinicalTrials.gov NCT03651271 adverse events section.

Sponsor's own description

This is an open-label, exploratory study to evaluate nivolumab with or without ipilimumab based on percentage of tumoral CD8 cells at the time of treatment in participants with varying advanced solid tumors. Participants who have a tumor with ≥ 15% CD8 cells (classified as CD8 high) will receive nivolumab monotherapy, and participants who have a tumor with \< 15% CD8 cells (classified as CD8 low) will receive ipilimumab in combination with nivolumab.

Publications & conference data

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

  1. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade.
    Morad G, Helmink BA, Sharma P, Wargo JA. · · 2021 · cited 1197× · PMID 34624224 · DOI 10.1016/j.cell.2021.09.020
  2. Prostate cancer immunotherapy: Improving clinical outcomes with a multi-pronged approach.
    Sridaran D, Bradshaw E, DeSelm C, Pachynski R, et al · · 2023 · cited 46× · PMID 37738978 · DOI 10.1016/j.xcrm.2023.101199
  3. The Immunotherapy and Immunosuppressive Signaling in Therapy-Resistant Prostate Cancer.
    Xu P, Wasielewski LJ, Yang JC, Cai D, et al · · 2022 · cited 29× · PMID 35892678 · DOI 10.3390/biomedicines10081778
  4. New insights into the important roles of tumor cell-intrinsic PD-1.
    Zheng H, Ning Y, Zhan Y, Liu S, et al · · 2021 · cited 25× · PMID 34326692 · DOI 10.7150/ijbs.60114
  5. Immunological facets of prostate cancer and the potential of immune checkpoint inhibition in disease management.
    Hansen SB, Unal B, Kuzu OF, Saatcioglu F. · · 2024 · cited 21× · PMID 39629128 · DOI 10.7150/thno.100555
  6. Immunotherapy for Prostate Cancer: A Current Systematic Review and Patient Centric Perspectives.
    Rehman LU, Nisar MH, Fatima W, Sarfraz A, et al · · 2023 · cited 21× · PMID 36835981 · DOI 10.3390/jcm12041446
  7. Immunotherapy in Prostate Cancer: State of Art and New Therapeutic Perspectives.
    Maselli FM, Giuliani F, Laface C, Perrone M, et al · · 2023 · cited 19× · PMID 37366915 · DOI 10.3390/curroncol30060432
  8. Update on immune-based therapy strategies targeting cancer stem cells.
    Izadpanah A, Mohammadkhani N, Masoudnia M, Ghasemzad M, et al · · 2023 · cited 14× · PMID 37698048 · DOI 10.1002/cam4.6520

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