GEN1046 for Cancer

Not currently recruiting at 64 trial locations
GT
Overseen ByGenmab Trial Information
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: Genmab
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a new antibody treatment called acasunlimab (GEN1046) for certain advanced or metastatic cancers. The trial tests acasunlimab alone and in combination with other cancer treatments like docetaxel and pembrolizumab. It targets individuals with cancers such as lung, cervical, or throat cancer that have not responded to other treatments. Participants must have a cancer diagnosis confirmed by a doctor and should not have other serious conditions, such as uncontrolled high blood pressure or active infections. The goal is to determine the best dose of acasunlimab and evaluate its effectiveness alone or with other treatments. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that you should not have had certain anti-cancer treatments within 28 days before starting the trial. It's best to discuss your current medications with the trial team to get specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that acasunlimab (GEN1046) has a manageable safety profile based on earlier studies. For example, when combined with pembrolizumab, another cancer drug, most patients did not experience side effects severe enough to stop treatment.

In another study, patients with certain types of cancer who received acasunlimab had a 69% chance of surviving for at least 12 months, suggesting the treatment did not cause serious harm over a year.

Acasunlimab remains under investigation. As this trial is in the early stages (Phase 1 and Phase 2), researchers are primarily focused on identifying the safest doses. While the treatment appears safe so far, further testing is necessary to fully understand its safety in humans.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about GEN1046, also known as acasunlimab, because it offers a novel approach to treating cancer by targeting both PD-L1 and 4-1BB pathways. This dual targeting mechanism is designed to enhance the body's immune response against cancer cells, potentially offering a more effective treatment than standard therapies like pembrolizumab or chemotherapy alone. Additionally, GEN1046 can be used as a monotherapy or in combination with existing treatments, providing flexibility and potentially improving outcomes for patients who may not respond to current options. This innovative approach could lead to more personalized and effective cancer treatments.

What evidence suggests that this trial's treatments could be effective for cancer?

Research has shown that acasunlimab, when used alone, yields promising results. In one study, 69% of patients survived after 12 months, and 30% showed a positive response to the treatment. This indicates that many patients lived longer and responded well. Acasunlimab boosts the immune system to fight cancer by targeting specific proteins on cancer cells.

In this trial, acasunlimab will be administered as monotherapy in the Dose Escalation arm. In the Expansion arm, acasunlimab will be given either as monotherapy or combined with other treatments, such as pembrolizumab, docetaxel, or pembrolizumab plus standard chemotherapy, in separate expansion cohorts. When combined with pembrolizumab, acasunlimab has shown a safety profile that patients can handle well. This combination aims to further strengthen the immune response. These early findings suggest that acasunlimab, either alone or with other treatments, could be effective against certain types of cancer.13567

Who Is on the Research Team?

SO

Study Official

Principal Investigator

Genmab

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced cancers (like lung, breast, bladder, or cervical cancer) that have relapsed or spread and can't be treated with standard therapies anymore. They should be in good physical condition (ECOG 0-1), have tumors that can be measured by scans, and their organs must function well. People who've had recent serious illnesses, infections needing IV drugs, severe side effects from immune treatments before, heart problems, uncontrolled blood pressure or autoimmune diseases cannot join.

Inclusion Criteria

My liver is functioning well.
I am fully active or can carry out light work.
My blood clotting ability is within normal ranges.
See 5 more

Exclusion Criteria

I stopped a cancer treatment due to severe side effects.
I haven't had any major organ or bone marrow transplants in the last 3 months.
I do not have severe heart problems like heart failure, chest pain, or irregular heartbeat.
See 11 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Acasunlimab is administered as monotherapy to determine the Recommended Phase 2 Dose (RP2D)

21 days
Weekly visits

Expansion

Acasunlimab is administered as monotherapy or in combination with docetaxel, pembrolizumab, or pembrolizumab + standard chemotherapy

21 weeks
Weekly visits initially, then every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

  • GEN1046
Trial Overview The trial tests acasunlimab alone and combined with other cancer drugs like docetaxel and pembrolizumab to see how safe they are for treating various solid tumors. It has two parts: dose escalation to find the right amount of drug to give safely and expansion where more people get the treatment at this dose to further check safety.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: ExpansionExperimental Treatment4 Interventions
Group II: Dose EscalationExperimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Genmab

Lead Sponsor

Trials
76
Recruited
15,300+

Dr. Jan van de Winkel

Genmab

Chief Executive Officer since 2010

PhD in Immunology, University of Utrecht

Dr. Judith Klimovsky

Genmab

Chief Medical Officer since 2019

MD, University of Copenhagen

BioNTech SE

Industry Sponsor

Trials
84
Recruited
120,000+

Prof. Dr. Ugur Sahin

BioNTech SE

Chief Executive Officer since 2008

MD from University of Cologne

Prof. Özlem Türeci

BioNTech SE

Chief Medical Officer since 2018

MD from Saarland University

Published Research Related to This Trial

In a study of 429 patients with treatment-refractory cancers, only 9 patients (2.1%) had solid tumors with a single genomic alteration suitable for N-of-One therapeutic strategies, highlighting the rarity of this condition.
Among these 9 patients, 66.7% experienced clinical benefits from matched therapies based on next-generation sequencing, with a median progression-free survival of 11.3 months, suggesting that personalized treatment can be effective even in complex cancer cases.
Case series of outcomes in advanced cancer patients with single pathway alterations receiving N-of-One therapies.Gupta, D., Kurzrock, R., Lee, S., et al.[2022]
In a study of 93 Chinese patients with advanced melanoma treated with PD-1 inhibitors, those who developed immune-related adverse events (irAEs) had significantly higher overall response rates (ORR) and disease control rates (DCR) compared to those without irAEs.
Patients experiencing three or more irAEs showed even better clinical outcomes, including longer progression-free survival and overall survival, suggesting that the presence of irAEs may indicate a more effective immune response to PD-1 therapy.
Association between immune-related adverse events and efficacy of PD-1 inhibitors in Chinese patients with advanced melanoma.Zhao, JJ., Wen, XZ., Ding, Y., et al.[2021]
In a meta-analysis of 4413 patients from 8 randomized controlled trials, PD-1/PD-L1 inhibitors showed a significantly lower risk of all-grade adverse events (66.20% vs. 86.08%) and high-grade adverse events (14.26% vs. 43.53%) compared to chemotherapy, indicating a better safety profile.
While PD-1/PD-L1 inhibitors are generally safer, they are associated with a unique set of immune-related adverse events (irAEs) that can be severe, such as pneumonitis and thyroid dysfunction, which clinicians need to monitor closely to manage patient quality of life.
Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials.Luo, W., Wang, Z., Tian, P., et al.[2021]

Citations

NCT06635824 | Trial to Evaluate Acasunlimab and ...The goal of this trial is to determine the efficacy and safety of acasunlimab (an experimental antibody also known as GEN1046 or DuoBody® PDL1x4-1BB) in ...
Acasunlimab (DuoBody-PD-L1x4-1BB) alone or in ...Results: As of Jan 9, 2024, 98 pts (63 with central PD-L1+ status) were enrolled: 23 (16) pts arm A; 39 (22) pts arm B; 36 (25) pts arm C. Among ...
Trial to Evaluate Acasunlimab and Pembrolizumab ...Trial to Evaluate Acasunlimab and Pembrolizumab Combination Superiority Over Standard of Care Docetaxel in Non-Small Cell Lung Cancer (ABBIL1TY NSCLC-06).
Safety and Efficacy Study of GEN1046 as a Single Agent or ...The goal of this clinical trial is to compare the safety and efficacy (how well the drug works) of acasunlimab (also known as GEN1046) when it is used alone ...
Study Details | NCT03917381 | GEN1046 Safety Trial in ...The goal of this trial is to learn about the antibody acasunlimab (an antibody also known as GEN1046) when it is used alone and when it is used together ...
GEN1046 Safety Trial in Patients With Malignant Solid ...The goal of this trial is to learn about the antibody acasunlimab (an antibody also known as GEN1046) when it is used alone and when it is used together ...
Investigational Acasunlimab (DuoBody® -PD-L1x4-1BB) in ...Initial data from the ongoing Phase 2 trial showed a 12-month overall survival rate of 69% and a median overall survival of 17.5 months in ...
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