Onfekafusp Alfa

Onfekafusp alfa, also known as L19TNF, is an innovative tumor-targeting human antibody-cytokine fusion protein being studied in clinical trials for the treatment of glioblastoma and soft tissue sarcoma. This article explores the ongoing research into this promising drug, including its potential efficacy, safety profile, and combination therapies with other anticancer agents.

Table of Contents

What is Onfekafusp Alfa?

Onfekafusp alfa, also known as L19TNF, is an innovative medication being studied for the treatment of various types of cancer[1][2][3][4]. It belongs to a class of drugs called antibody-cytokine fusion proteins. This means it combines two different components: an antibody that targets specific cancer cells and a cytokine (a type of protein) that helps stimulate the immune system to fight cancer.

How Does Onfekafusp Alfa Work?

Onfekafusp alfa works by targeting tumor cells and delivering a powerful immune-stimulating substance directly to the cancer site. The L19 part of the drug is an antibody that specifically recognizes and attaches to structures found in tumor blood vessels. The TNF (Tumor Necrosis Factor) part is a cytokine that can activate the immune system and potentially kill cancer cells. By combining these two elements, onfekafusp alfa aims to deliver a targeted attack on cancer while minimizing effects on healthy tissues[3].

Conditions Treated with Onfekafusp Alfa

Onfekafusp alfa is being investigated for the treatment of several types of cancer, including:

  • Glioblastoma: This is an aggressive type of brain cancer. Onfekafusp alfa is being studied in patients with newly diagnosed glioblastoma and in those whose glioblastoma has returned after initial treatment[1][4].
  • Soft Tissue Sarcoma: This is a group of cancers that develop in the body’s soft tissues, such as muscles, fat, and blood vessels. Onfekafusp alfa is being tested in patients with advanced or metastatic (spread to other parts of the body) soft tissue sarcoma[2][3].

Clinical Trials and Research

Onfekafusp alfa is currently being studied in several clinical trials to determine its safety and effectiveness. These trials are investigating the drug in different scenarios:

  • In combination with other cancer drugs like lomustine, dacarbazine, and doxorubicin[1][2][3].
  • As part of a treatment regimen that includes chemotherapy and radiation therapy[4].
  • Comparing its effectiveness to standard treatments alone[3].

These trials are measuring various outcomes, including how long patients live without their cancer getting worse (progression-free survival), overall survival rates, and how well tumors respond to the treatment[2][3].

How is Onfekafusp Alfa Administered?

Onfekafusp alfa is typically given as an intravenous (IV) infusion, which means it’s delivered directly into the bloodstream through a vein. The exact dosing schedule can vary depending on the specific clinical trial and the condition being treated. Some common patterns include:

  • Given on days 1, 3, and 5 of a treatment cycle[1][2].
  • Administered every 3 weeks[3].
  • Combined with other treatments like chemotherapy or radiation therapy[4].

The dose of onfekafusp alfa is usually calculated based on the patient’s body weight or body surface area.

Potential Side Effects

As onfekafusp alfa is still in clinical trials, all of its potential side effects are not yet fully known. However, researchers are closely monitoring patients for any adverse reactions. Some areas of focus include:

  • General side effects: These may include typical cancer treatment side effects like fatigue, nausea, or changes in blood cell counts[2].
  • Liver effects: Researchers are monitoring for any signs of drug-induced liver injury[4].
  • Immune system reactions: Since onfekafusp alfa interacts with the immune system, there’s a possibility of immune-related side effects[2].

It’s important to note that in clinical trials, patients are closely monitored for any side effects, and the benefits and risks of the treatment are carefully evaluated[3].

Trial Name Cancer Type Phase Combination Therapy Primary Outcomes
NCT05304663 Glioblastoma I Lomustine Safety and efficacy of different administration sequences
NCT04733183 Soft Tissue Sarcoma II Dacarbazine Progression-free survival at 3, 6, 9, and 12 months
NCT04650984 Soft Tissue Sarcoma III Doxorubicin Median progression-free survival
NCT04443010 Glioblastoma I/II Temozolomide Dose-limiting toxicity and overall survival rate

Ongoing Clinical Trials on Onfekafusp Alfa

  • A study of onfekafusp alfa and bifikafusp alfa injected into tumors for patients with advanced skin squamous cell cancer who did not respond to or could not tolerate previous treatment

    Recruiting

    2 1 1
    Germany Greece Italy Spain
  • Testing bifikafusp alfa and onfekafusp alfa injections in patients with locally advanced basal cell carcinoma

    Recruiting

    2 1 1
    Germany Greece Italy Spain
  • Study of bifikafusp alfa and onfekafusp alfa injected into tumors for patients with locally advanced basal cell carcinoma who progressed on or cannot tolerate systemic treatment

    Recruiting

    2 1 1
    Investigated diseases:
    Germany Greece Italy Spain
  • Testing bifikafusp alfa, onfekafusp alfa, and pembrolizumab combination in patients with advanced melanoma that did not respond to previous immunotherapy

    Recruiting

    2 1 1 1
    Germany Italy
  • Study on the Effectiveness of L19IL2 and L19TNF Injections with Surgery for Patients with Stage IIIB/C Melanoma

    Recruiting

    3 1 1
    Germany Italy Spain Sweden
  • Study of L19TNF (onfekafusp alfa) with temozolomide chemoradiotherapy for newly diagnosed glioblastoma patients

    Not yet recruiting

    1 1 1 1
    Investigated diseases:
    Germany Italy
  • Study of L19TNF and Lomustine for Patients with Recurrent or Progressive Glioblastoma

    Not yet recruiting

    2 1 1 1
    Investigated diseases:
    Investigated drugs:
    Germany Italy
  • Study on L19IL2 and L19TNF Treatment Before Surgery for Patients with Advanced Melanoma

    Not recruiting

    3 1 1
    Investigated diseases:
    France Germany Italy Poland
  • Study of L19IL2 and L19TNF for Patients with Advanced Basal Cell Carcinoma or Cutaneous Squamous Cell Carcinoma Not Eligible for Surgery or Radiation

    Not recruiting

    2 1 1
    Germany Poland
  • Study of L19IL2 and L19TNF for Patients with Skin Cancer Suitable for Direct Tumor Injection

    Not recruiting

    2 1 1
    France Italy Spain

Glossary

  • Glioblastoma: A fast-growing and aggressive type of brain cancer that forms from glial cells (cells that support and protect nerve cells).
  • Soft Tissue Sarcoma: A type of cancer that develops in soft tissues such as muscles, tendons, fat, lymph vessels, blood vessels, and nerves.
  • Progression-Free Survival (PFS): The length of time during and after treatment that a patient lives with the disease but it does not get worse.
  • Overall Survival (OS): The length of time from either the date of diagnosis or the start of treatment for a disease that patients are still alive.
  • Objective Response Rate (ORR): The proportion of patients whose cancer shrinks or disappears after treatment.
  • Dose-Limiting Toxicity (DLT): Side effects of a drug that are severe enough to prevent an increase in dose or level of treatment.
  • RECIST: Response Evaluation Criteria in Solid Tumors, a standard way to measure how well a cancer patient responds to treatment.
  • Chemoradiotherapy: A type of cancer treatment that combines chemotherapy with radiation therapy.
  • Temozolomide (TMZ): A chemotherapy drug used to treat certain types of brain cancer, including glioblastoma.
  • Dacarbazine (DTIC): A chemotherapy drug used to treat various types of cancer, including soft tissue sarcoma.

References