Title
A Phase I/II, First-In-Human, Multi-Part, Open-Label, Multiple-Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of DF1001 in Patients With Locally Advanced or Metastatic Solid Tumors, and Expansion in Selected Indications

Description
DF1001-001 is a study of a new molecule that targets natural killer (NK) cells and T-cell activation signals to specific receptors on cancer cells. The study will occur in two phases. The first phase will be a dose escalation phase, enrolling patients with various types of solid tumors that express human epidermal growth factor receptor 2 (HER2). Two combination therapy cohorts will be opened for enrollment, DF1001 + nivolumab and DF1001 + Nab paclitaxel. The second phase will include a dose expansion using the best dose selected from the first phase of the study. Multiple cohorts will be opened with eligible patients having either selected solid tumors, or solid tumors expressing high levels of HER2.

Objective
Primary Objectives
Dose Escalation Part:

To assess the safety and tolerability of DF1001, and to determine the MTD of DF1001 in patients with advanced (unresectable, recurrent or metastatic) solid tumors for whom no effective standard therapy exists or have recurrent disease or are intolerant of standard therapy(ies).

To assess the Overall Response Rate (ORR) according to the RECIST 1.1 per an IERC.

To characterize the PK of DF1001.

To evaluate immunogenicity of DF1001, and to correlate to its exposure and clinical activity.

To assess Duration of Response (DOR) of DF1001 per an IERC.

To assess Best Overall Response (BOR) by IERC.

To assess Progression Free Survival (PFS) for DF1001 per an IERC.

To assess Overall Survival (OS) time.

To assess the safety of DF1001 in Combination therapy with pembrolizumab.

Treatment The study consists of 2 parts:

Dose Escalation Part, Phase I, which will be divided into the following 3 phases:

Accelerated titration

“3+3” dose escalation

Combination therapy dose escalation:


Combination with nivolumab

Combination with Nab paclitaxel


Safety/PK/PD expansion cohorts


Monotherapy

Combination with nivolumab

Combination with Nab paclitaxel

Urothelial bladder cancer (UBC)

Metastatic breast cancer (MBC)

Basket solid tumors with high HER2 expression (HER2 3+)

Key Eligibility For full eligibility, please see this study's ClinicialTrials.gov record.

Applicable Disease Sites
Anal; Any Site; Bladder; Brain/Central Nervous System; Breast; Cervix; Colon and Rectum; Endocrine cancers; Esophagus; Gastrointestinal cancers, other; Genitourinary cancers, other; Head and Neck; Ill-Defined Sites; Kidney; Liver; Lung; Melanoma/Skin cancer; Ovary; Pancreas; Prostate; Sarcoma; Stomach; Thyroid; Unknown Sites; Uterus

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital