Related Experiment Video

Updated: Jan 17, 2026

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
10:27

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

Published on: July 25, 2020

7.8K

Gemogenovatucel-T Advantage in Clonal Tumor Mutation Burden-High Ovarian Cancer

Robert L Coleman1, Rodney Rocconi2, Bradley J Monk3

  • 1Texas Oncology, Shenandoah, TX.

JCO Precision Oncology
|January 14, 2026
PubMed
Abstract

Insights

Maintenance therapy with gemogenovatucel-T significantly improved overall survival for ovarian cancer patients with high clonal tumor mutation burden and homologous recombination-proficient tumors. This targeted approach offers a new hope for advanced ovarian cancer treatment.

Area of Science:

  • Oncology
  • Genomics
  • Clinical Trials

Background:

  • Standard frontline treatments for advanced ovarian cancer, including bevacizumab, PARP inhibitors, and PD-1/PD-L1 inhibitors, have not improved overall survival in patients with homologous recombination-proficient (HRP) tumors.
  • Identifying specific mutation signatures associated with improved outcomes is crucial for developing more effective therapies.

Purpose of the Study:

  • To determine the mechanistic mutation signatures associated with overall survival (OS) advantage in patients with ovarian cancer.
  • To evaluate the efficacy of gemogenovatucel-T as maintenance therapy in patients with stage IIIb-IV ovarian cancer who have a homologous recombination-proficient (HRP) profile and high clonal tumor mutation burden (cTMB-H).

Main Methods:

  • A whole-exome sequencing bioinformatic pipeline was developed to analyze 91 patients from the VITAL trial.
  • Patients with stage IIIb-IV ovarian cancer, HRP profile, and cTMB-H were hypothesized to benefit from gemogenovatucel-T maintenance therapy.
  • Overall survival was assessed using the Kaplan-Meier method in a randomized, double-blind, placebo-controlled phase II trial.

Main Results:

  • Patients with cTMB-H/HRP ovarian cancer treated with gemogenovatucel-T had a median OS of 68 months compared to 19 months for placebo (hazard ratio [HR], 0.23; 95% CI, 0.06 to 0.83; P = .008).
  • No OS advantage was observed in cTMB-H patients with a non-HRP profile (HR, 0.99; 95% CI, 0.39 to 2.47; P = .488).
  • No grade 3 treatment-related toxicity was observed in the gemogenovatucel-T group during 8.4 years of follow-up.

Conclusions:

  • Maintenance therapy with gemogenovatucel-T demonstrated a significant overall survival advantage in adult females with newly diagnosed, advanced stage ovarian cancer.
  • The benefit was observed in patients with HRP status and a cTMB-H profile who achieved complete response after surgery and frontline chemotherapy.
  • These findings support gemogenovatucel-T as a potential targeted maintenance therapy for a specific subgroup of ovarian cancer patients.

More Related Videos

Somatic Genome-Engineered Mouse Models Using In Vivo Microinjection and Electroporation08:06

Somatic Genome-Engineered Mouse Models Using In Vivo Microinjection and Electroporation

Published on: May 5, 2023

2.4K
Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer09:08

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

7.2K

Related Concept Videos

Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
11.1K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.4K
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...
8.6K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
7.0K
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
14.6K