Clinical trial NCT03543813: PROCLAIM-CX-2029: A Trial to Find Safe and Active Doses of an Investigational Drug CX-2029 for Patients With Solid Tumors or DLBCL
Official title: A Phase 1-2, First-in-Human Study of CX-2029 in Adults With Metastatic or Locally Advanced Unresectable Solid Tumors or Diffuse Large B-cell Lymphomas (PROCLAIM-CX-2029)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Solid Tumor, Adult
Head and Neck Cancer
Non Small Cell Lung Cancer
Diffuse Large B Cell Lymphoma
Esophageal Cancer
Keywords: cancer
solid tumor
DLBCL
CX-2029
PROBODY™ Therapeutic
Drug Conjugate
Antibody drug conjugate
CD71
Transferrin receptor 1
Lead sponsor: CytomX Therapeutics
Sponsor class: INDUSTRY
First posted: 2018-06-01
Enrollment: 133
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this first-in-human study of CX-2029 is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of CX-2029 in adult subjects with metastatic or locally advanced unresectable solid tumors or diffuse large B-cell lymphoma (DLBCL). The antitumor activity of CX-2029 will be evaluated in subjects with head and neck squamous cell carcinoma (HNSCC), DLBCL, non-small cell lung cancer (NSCLC) (squamous cell histology only), or esophageal (esophageal adenocarcinoma \[EAC\], esophageal squamous cell carcinoma \[ESCC\], or gastroesophageal \[GE\] junction) cancer.

PROCLAIM: PRObody CLinical Assessment In Man CX-2029 clinical trial 001

PROBODY is a trademark of CytomX Therapeutics, Inc

Detailed description: This is an open-label, Phase 1-2, first-in-human study for CX-2029 in subjects with metastatic or locally advanced unresectable solid tumors or Diffuse large B-cell lymphoma (DLBCL) without approved life-prolonging treatment options for their malignancy.

The study is divided into 3 parts (arms), as follows:

* Part A: Dose escalation and determination of the Maximum tolerated dose (MTD) and/or Recommended Phase 2 dose (RP2D)
* Part B: Characterization of CX-2029 in the Tumor microenvironment (TME) in subjects with select tumor types using previously cleared dose levels from Part A
* Part C: Expansions in select tumor types at the MTD/RP2D as established in Part A

Eligibility criteria: Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of metastatic or locally advanced unresectable tumors
2. Patients demonstrating disease progression after treatment with approved therapies that are known to confer life-prolonging benefit, or who are intolerant to or have declined treatment
3. Agreement to provide mandatory archival tissue or fresh biopsy
4. At least 18 years of age
5. For Arm A, histologically or cytologically confirmed metastatic or locally advanced unresectable solid tumor
6. For Arms B and C, histologically or cytologically confirmed metastatic or locally advanced unresectable HNSCC, DLBCL, NSCLC (squamous cell histology only), or esophageal (EAC, ESCC, or GE junction) cancer
7. Additional inclusion criteria may apply

Exclusion Criteria:

1. Neuropathy \> Grade 1
2. Serious concurrent illness, including clinically relevant active infection
3. Clinically significant iron metabolism disorders (eg, sickle cell anemia)
4. Significant cardiac disease such as recent myocardial infarction
5. History of multiple sclerosis or other demyelinating disease, Eaton-Lambert syndrome (para-neoplastic syndrome), history of hemorrhagic or ischemic stroke within the last 6 months, or alcoholic liver disease;
6. Non-healing wound(s) or ulcer(s) except for ulcerative lesions caused by the underlying neoplasm;
7. History of severe allergic or anaphylactic reactions to previous monoclonal antibody therapy;
8. Currently receiving anticoagulation therapy with warfarin;
9. Major surgery (requiring general anesthesia) within 3 months prior to dosing.
10. Hepatic impairment which is moderate (Child-Pugh B) or severe (Child-Pugh C)
11. Transfusion dependent anemia with transfusion dependency of ≥3 months
12. Use of iron chelators
13. Additional exclusion criteria may apply

Primary outcomes:
measure: The number of subjects experiencing a dose-limiting toxicity at various dose levels when given CX-2029 as a monotherapy
timeFrame: 21 days (dose-limiting toxicity period)
Secondary outcomes:
measure: The percentage of subjects experiencing anti-cancer activity (ORR) at various dose levels when given CX-2029 as a monotherapy
timeFrame: 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Encinitas
country: United States
facility: California Cancer Associates for Research and Excellence
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Lake Mary
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Hattiesburg
country: United States
facility: Forrest General Cancer Center
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University - St. Louis
state: Missouri
city: New York
country: United States
facility: New York University (NYU) Clinical Cancer Center
state: New York
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: The Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Jongno-gu
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
state: Jongno-gu
city: Seoul
country: Korea, Republic of
facility: Severance Hospital- Yonsei Cancer Center
state: Seodaemun-gu
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario La Paz, Servicio de Oncología
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal, START Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Quiron de Madrid
city: Withington
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: Manchester Greater
city: Glasgow
country: United Kingdom
facility: Beatson, West of Scotland Cancer Centre
Study officials:
affiliation: CytomX Therapeutics, Inc.
name: Monika Vainorius, M.D.
role: STUDY_DIRECTOR
References: