PROCLAIM-CX-2029: A Trial to Find Safe and Active Doses of an Investigational Drug CX-2029 for Patients With Solid Tumors or DLBCL

Study Overview
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Brief Summary
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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
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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

Official Title
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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)

Conditions
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Solid Tumor, Adult, Head and Neck Cancer, Non Small Cell Lung Cancer, Diffuse Large B Cell Lymphoma, Esophageal Cancer

Intervention / Treatment
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* Drug: CX-2029


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed diagnosis of metastatic or locally advanced unresectable tumors 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 Agreement to provide mandatory archival tissue or fresh biopsy At least 18 years of age For Arm A, histologically or cytologically confirmed metastatic or locally advanced unresectable solid tumor 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 Additional inclusion criteria may apply Exclusion Criteria: Neuropathy > Grade 1 Serious concurrent illness, including clinically relevant active infection Clinically significant iron metabolism disorders (eg, sickle cell anemia) Significant cardiac disease such as recent myocardial infarction 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; Non-healing wound(s) or ulcer(s) except for ulcerative lesions caused by the underlying neoplasm; History of severe allergic or anaphylactic reactions to previous monoclonal antibody therapy; Currently receiving anticoagulation therapy with warfarin; Major surgery (requiring general anesthesia) within 3 months prior to dosing. Hepatic impairment which is moderate (Child-Pugh B) or severe (Child-Pugh C) Transfusion dependent anemia with transfusion dependency of ≥3 months Use of iron chelators Additional exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CX-2029 Escalation<br>Dose Escalation and Determination | Drug: CX-2029<br>* CX-2029 Monotherapy<br>|
| Experimental: CX-2029 Biomarker<br>Characterization of CX-2029 in the tumor microenvironment in subjects with select tumor types | Drug: CX-2029<br>* CX-2029 Monotherapy<br>|
| Experimental: CX-2029 Expansion<br>Evaluate antitumor activity of CX-2029 | Drug: CX-2029<br>* CX-2029 Monotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of subjects experiencing a dose-limiting toxicity at various dose levels when given CX-2029 as a monotherapy |  | 21 days (dose-limiting toxicity period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of subjects experiencing anti-cancer activity (ORR) at various dose levels when given CX-2029 as a monotherapy |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer, solid tumor, DLBCL, CX-2029, PROBODY™ Therapeutic, Drug Conjugate, Antibody drug conjugate, CD71, Transferrin receptor 1