Clinical trial NCT02375958: PCA062 in pCAD-positive Tumors.
Official title: A Phase 1 Multi-center, Open-label Dose Escalation and Expansion Study of PCA062 Administered Intravenously in Adult Patients With p-CAD Positive Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Triple Negative Breast Cancer
Head & Neck Cancer
Esophageal Cancer
Keywords: PCA062
Triple Negative Breast Cancer
Head & Neck Cancer
Esophageal Cancer
pCAD, pcadherin, solid-tumors
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-03-03
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A first-in-human sttudy using PCA062 in patients with p-CAD positive solid tumors.


Eligibility criteria: Inclusion criteria:

1. Male or female ≥ 18 years of age
2. Documented pCAD expressing tumor cells with the exception of HNSCC and ESCC. An archived tumor sample collected within 36 months prior to baseline if available, or a new tumor biopsy sample must be available for molecular pre-screening.
3. Consent for a tumor biopsy at screening
4. Progressive disease and no effective therapy exists
5. Measurable disease as per RECIST v1.1 criteria
6. ECOG Performance status of ≤ 2

Exclusion criteria:

1. CNS metastatic involvement
2. Clinically significant cardiac, respiratory, gastrointestinal, renal, hepatic or neurological conditions.
3. A history of serious allergic reactions, which in the opinion of the investigator pose an increased risk of serious infusion reactions.
4. Monocular vision or has media opacities or any other condition that precludes monitoring of the retina or the fundus, or has a history of ophthalmology exam with retina or cornea abnormalities
5. Previously treated with anti-pCAD biologic therapies.
6. Received anti-cancer therapies within the following time frames prior to the first dose of study treatment:

   * Conventional cytotoxic chemotherapy: ≤4 weeks
   * Biologic therapy (eg, antibodies), other than ADCs: ≤4 weeks
   * Non-cytotoxic small molecule therapeutics: ≤5 T1/2 or ≤2 weeks (whichever is longer)
   * Other investigational agents: ≤4 weeks
   * Radiation therapy (palliative setting is allowed.): ≤4 weeks
   * Major surgery: ≤2 weeks
7. Patient has out of range laboratory values defined as:

   * Hematological values:
   * Absolute neutrophil count (ANC) \<1.5 x 109/L
   * Hemoglobin (Hgb) \<9 g/dL
   * Platelets \<100 x 109/L
   * Hepatic and renal function
   * Total bilirubin \>1.5 x upper limit of normal (ULN). For patients with Gilbert's syndrome, total bilirubin \>2.5 x ULN.
   * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 x ULN for patients without tumor involvement of the liver or \>5 x ULN for patients with tumor involvement of the liver.
   * Serum creatinine \>1.5 x ULN and/or measured creatinine clearance \< 40 ml/min

Primary outcomes:
measure: Incidence rate of dose limiting toxicities
timeFrame: 28 days
Secondary outcomes:
measure: Incidence and severity of serious/adverse events
timeFrame: Duration of study (each treatment cycle = 14 days)
measure: Pharmacokinetic parameter Cmax
timeFrame: 84 days
measure: Presence of PCA062 anti-bodies
timeFrame: 84 days
measure: Overall response rate
timeFrame: Duration of study (each treatment cycle = 14 days)
measure: Duration of response
timeFrame: Duration of study (each treatment cycle = 14 days)
measure: Progression free survival
timeFrame: 18 months
measure: Disease control rate
timeFrame: 18 months
measure: Best overall response
timeFrame: Duration of study (each treatment cycle = 14 days)
measure: Pharmacokinetic paramater Tmax
timeFrame: 84 days
Other outcomes:
Locations:
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Novartis Investigative Site
state: Texas
city: Villejuif Cedex
country: France
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Koto ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Duca M, Lim DW, Subbiah V, Takahashi S, Sarantopoulos J, Varga A, D'Alessio JA, Abrams T, Sheng Q, Tan EY, Rosa MS, Gonzalez-Maffe J, Sand-Dejmek J, Fabre C, Martin M. A First-in-Human, Phase I, Multicenter, Open-Label, Dose-Escalation Study of PCA062: An Antibody-Drug Conjugate Targeting P-Cadherin, in Patients With Solid Tumors. Mol Cancer Ther. 2022 Apr 1;21(4):625-634. doi: 10.1158/1535-7163.MCT-21-0652.