Related Experiment Video

Updated: Jul 8, 2026

The Use of Reverse Phase Protein Arrays (RPPA) to Explore Protein Expression Variation within Individual Renal Cell Cancers
12:22

The Use of Reverse Phase Protein Arrays (RPPA) to Explore Protein Expression Variation within Individual Renal Cell Cancers

Published on: January 22, 2013

A Phase 1b/2 Study of Talazoparib and Axitinib in Patients with Advanced Clear-cell Renal Cell Carcinoma

Ritesh R Kotecha1, Sahil D Doshi2, Andrea Knezevic3

  • 1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weil Cornell Medical College, New York, NY, USA.

European Urology Oncology
|March 30, 2025
PubMed

Insights

This study combined axitinib and talazoparib for advanced clear-cell renal cell carcinoma (ccRCC). The combination showed safety but did not meet efficacy goals, with most patients progressing.

Area of Science:

  • Oncology
  • Translational Research
  • Clinical Trials

Background:

  • VHL gene inactivation in clear-cell renal cell carcinoma (ccRCC) promotes tumor growth via HIF accumulation and angiogenesis.
  • Treatment-refractory ccRCC remains a significant clinical challenge, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To evaluate the safety and antitumor activity of combining axitinib (VEGFR-targeted tyrosine kinase inhibitor) with talazoparib (PARP inhibitor) in patients with advanced ccRCC.
  • To determine the recommended Phase 2 dose (RP2D) for this combination therapy.

Main Methods:

  • A Phase 1b/2 study design involving dose escalation (3+3) followed by dose expansion.
  • Patients received escalating doses of talazoparib with a fixed dose of axitinib.
  • Primary endpoints included RP2D determination and objective response rate.

Main Results:

  • The RP2D was established as talazoparib 1 mg daily and axitinib 5 mg twice daily.
  • At the RP2D, 13 out of 14 patients discontinued due to disease progression, with a median progression-free survival of 6.1 months.
  • Grade 3+ treatment-emergent adverse events occurred in 56% of patients, most commonly diarrhea, nausea, and anemia.

Conclusions:

  • The combination of axitinib and talazoparib demonstrated an acceptable safety profile in treatment-refractory ccRCC.
  • Despite safety, the combination did not achieve the predefined efficacy threshold for further clinical development.
  • This represents the first investigation of a VEGFR inhibitor plus a PARP inhibitor in ccRCC.
Keywords:
AxitinibRenal cell carcinomaTalazoparib

More Related Videos

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

Establishment and Characterization of Patient-Derived Xenograft Models of Anaplastic Thyroid Carcinoma and Head and Neck Squamous Cell Carcinoma06:08

Establishment and Characterization of Patient-Derived Xenograft Models of Anaplastic Thyroid Carcinoma and Head and Neck Squamous Cell Carcinoma

Published on: June 2, 2023

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Treatment Resistent Cancers02:56

Treatment Resistent Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Clinical Trials01:16

Clinical Trials

Clinical trials are prospective experimental studies conducted on humans to determine the safety and efficacy of treatments, drugs, diet methods, and medical devices. Using statistics in clinical trials enables researchers to derive reasonable and accurate conclusions from the collected data, allowing them to make wise decisions in uncertain situations. In medical research, statistical methods are crucial for preventing errors and bias.
There are four phases in a clinical trial. A phase one...
Clinical Trials: Overview01:11

Clinical Trials: Overview

Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...