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NCT03181308

Study of Carotuximab (TRC105) Plus Nivolumab in Patients With Metastatic NSCLC

Completed Phase 1 Results posted Last updated 24 June 2020
What this trial tests

Phase 1 trial testing Carotuximab (TRC105) in Carcinoma, Non-Small-Cell Lung in 11 participants. Completed in 22 July 2019.

Timeline
9 November 2017
Primary endpoint
22 July 2019
22 July 2019

Quick facts

Lead sponsorTracon Pharmaceuticals Inc.
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment11
Start date9 November 2017
Primary completion22 July 2019
Estimated completion22 July 2019
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Tracon Pharmaceuticals Inc. — full company profile →

Who can join

18 and older, any sex, with Carcinoma, Non-Small-Cell Lung. 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 With Dose Limiting Toxicity (DLT) Primary · Approximately 2-8 months

For DLT evaluation, severity (grade) was classified according to common terminology criteria for adverse events version 4.03 (CTCAE v4.03). DLTs were defined as grade 4 neutropenia persisting for ≥ 5 days, Febrile neutropenia: Grade 4 neutropenia with fever \>38.5ºC both sustained over a ≥24-hour period, neutropenic infection (grade ≥ 3 neutropenia with grade ≥ 3 infection), anemia ≥ grade 4, Grade ≥4 thrombocytopenia or Grade ≥3 thrombocytopenia with Grade ≥3 hemorrhage, or grade 3 or 4 nonhematologic toxicity with the following exceptions: asymptomatic electrolyte abnormality that is correct

GroupValue95% CI
8 mg/kg TRC105 + Nivolumab0
10 mg/kg TRC105 + Nivolumab0
8 mg/kg TRC105 + Nivolumab3
10 mg/kg TRC105 + Nivolumab0
8 mg/kg TRC105 + Nivolumab0
10 mg/kg TRC105 + Nivolumab0
8 mg/kg TRC105 + Nivolumab0
10 mg/kg TRC105 + Nivolumab8
Response Rate Secondary · Approximately 2-8 months

Preliminary evidence of antitumor activity of carotuximab (TRC105) plus nivolumab will be evaluated, by assessing response rate and progression-free survival. The best response was measured to iRECIST by MRI or CT scans for each patient with measurable disease who received at least 1 dose of study drug.

iSD (Immune Stable Disease) Best Response
GroupValue95% CI
8 mg/kg TRC105 + Nivolumab0
10 mg/kg TRC105 + Nivolumab4
iPR (Immune Partial Response) Best Response
GroupValue95% CI
8 mg/kg TRC105 + Nivolumab1
10 mg/kg TRC105 + Nivolumab0
iPD (Immune Progressive Disease) Best Response
GroupValue95% CI
8 mg/kg TRC105 + Nivolumab0
10 mg/kg TRC105 + Nivolumab0
iCR (Immune Complete Response) Best Response
GroupValue95% CI
8 mg/kg TRC105 + Nivolumab0
10 mg/kg TRC105 + Nivolumab0
iUPD (Unconfirmed Immune PD) Best Response
GroupValue95% CI
8 mg/kg TRC105 + Nivolumab2
10 mg/kg TRC105 + Nivolumab3
Trough Carotuximab (TRC105) Concentrations Secondary · 8 weeks

Trough (pre-dose) serum carotuximab (TRC105) concentrations will be measured using validated ELISA methods.

GroupValue95% CI
8 mg/kg TRC105 + Nivolumab6523346400 – 82700
10 mg/kg TRC105 + Nivolumab9360072600 – 121000
Development of Immunogenicity Antibodies Secondary · Approximately 2-8 months

Number of Participants with carotuximab (TRC105) anti-product antibodies (APA)

GroupValue95% CI
8 mg/kg TRC105 + Nivolumab0
10 mg/kg TRC105 + Nivolumab0
8 mg/kg TRC105 + Nivolumab3
10 mg/kg TRC105 + Nivolumab3
Trough Nivolumab Concentrations Secondary · Approximately 2-8 months

Trough (pre-dose) serum nivolumab concentrations will be measured using validated ELISA methods.

GroupValue95% CI
8 mg/kg TRC105 + Nivolumab6523346400 – 82700
10 mg/kg TRC105 + Nivolumab9360072600 – 121000

Adverse events — posted to ClinicalTrials.gov

Time frame: From screening until completion of follow-up, on average 6 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

8 mg/kg TRC105 + Nivolumab
Serious: 0/3 (0%)
Deaths: 0/3
10 mg/kg TRC105 + Nivolumab
Serious: 4/8 (50%)
Deaths: 0/8

Serious adverse events (6 terms)

ReactionSystem8 mg/kg TRC105 + Nivolumab10 mg/kg TRC105 + Nivolumab
Cancer painNeoplasms benign, malignant and unspecified (incl cysts and polyps)
PneumoniaInfections and infestations
Retinal haemorrhageEye disorders
Retinal vein occlusionEye disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Vascular access complicationVascular disorders
Other adverse events (74 terms — click to expand)

ReactionSystem8 mg/kg TRC105 + Nivolumab10 mg/kg TRC105 + Nivolumab
HeadacheNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
Weight decreasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
TelangiectasiaSkin and subcutaneous tissue disorders
EmbolismVascular disorders
AnaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
Gingival bleedingGastrointestinal disorders
FatigueGeneral disorders
PyrexiaGeneral disorders
Lung infectionInfections and infestations
PneumoniaInfections and infestations
SinusitisInfections and infestations
Upper respiratory infectionInfections and infestations
MigraineNervous system disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Sinus tachycardiaCardiac disorders
Ear painEar and labyrinth disorders
TinnitusEar and labyrinth disorders
VertigoEar and labyrinth disorders
BlepharitisEye disorders
Blindness transientEye disorders
Retinal tearEye disorders
Vision blurredEye disorders
ConstipationGastrointestinal disorders
Dry mouthGastrointestinal disorders
StomatitisGastrointestinal disorders
Tongue blisteringGastrointestinal disorders
Face oedemaGeneral disorders
Non-cardiac chest painGeneral disorders
Oedema peripheralGeneral disorders
BronchitisInfections and infestations
Oral candidiasisInfections and infestations
Urinary tract infectionInfections and infestations
Vaginal infectionInfections and infestations
Infusion related reactionInjury, poisoning and procedural complications
Alanine aminotransferase increasedInvestigations

Most-reported serious reactions: Cancer pain, Pneumonia, Retinal haemorrhage, Retinal vein occlusion, Pneumonitis, Vascular access complication.

Data from ClinicalTrials.gov NCT03181308 adverse events section.

Sponsor's own description

This is a multi-center, open-label, nonrandomized, dose-escalation, Phase 1b study of carotuximab in combination with standard dose nivolumab in patients with NSCLC that has progressed on or after platinum-based chemotherapy or PD-1/PD-L1 checkpoint inhibition, as a single agent or with chemotherapy.

Publications & conference data

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

  1. Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation.
    Wu M, Huang Q, Xie Y, Wu X, et al · · 2022 · cited 336× · PMID 35279217 · DOI 10.1186/s13045-022-01242-2
  2. Cancer stem cell-targeted chimeric antigen receptor (CAR)-T cell therapy: Challenges and prospects.
    Masoumi J, Jafarzadeh A, Abdolalizadeh J, Khan H, et al · · 2021 · cited 56× · PMID 34386318 · DOI 10.1016/j.apsb.2020.12.015
  3. New Strategies Using Antibody Combinations to Increase Cancer Treatment Effectiveness.
    Corraliza-Gorjón I, Somovilla-Crespo B, Santamaria S, Garcia-Sanz JA, et al · · 2017 · cited 49× · PMID 29312320 · DOI 10.3389/fimmu.2017.01804
  4. Endoglin Targeting: Lessons Learned and Questions That Remain.
    Liu Y, Paauwe M, Nixon AB, Hawinkels LJAC. · · 2020 · cited 26× · PMID 33375670 · DOI 10.3390/ijms22010147
  5. The Dual Effect of the BMP9-ALK1 Pathway in Blood Vessels: An Opportunity for Cancer Therapy Improvement?
    Ayuso-Íñigo B, Méndez-García L, Pericacho M, Muñoz-Félix JM. · · 2021 · cited 13× · PMID 34771575 · DOI 10.3390/cancers13215412

Verify or expand the search:

Other recruiting trials for Carcinoma, Non-Small-Cell Lung

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