GEN1042 for Advanced Cancers

Not currently recruiting at 95 trial locations

Overseen By Genmab Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Genmab

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Autoimmune disease, Pneumonitis, Allergic reactions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with certain advanced cancers. Researchers aim to understand how the antibody GEN1042 (a bispecific antibody) works alone and in combination with another cancer drug, pembrolizumab, sometimes alongside chemotherapy. The trial targets individuals with advanced or metastatic cancers, such as melanoma, lung, and certain head and neck cancers, who have not responded to standard treatments. Participants should have cancers that are difficult to remove or have recurred after treatment, with no other standard treatment options available. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial requires stopping anti-cancer agents at least 21 days or 5 half-lives before starting GEN1042. Other medications, like corticosteroids or immunosuppressive drugs, must be stopped 14 days before treatment. The protocol does not specify other medications, so consult your doctor.

Will I have to stop taking my current medications?

The trial requires that you stop taking any anti-cancer agents at least 21 days before starting GEN1042, or after at least 5 half-lives of the drug, whichever is shorter. If you are on systemic corticosteroids or other immunosuppressive medications, you must stop them 14 days before the trial treatment.

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

Research has shown that GEN1042, a new treatment being tested for advanced cancers, is generally safe. In earlier studies, patients tolerated the treatment well and showed early signs of tumor response. Most participants did not experience severe side effects.

When tested alone and with another cancer drug, pembrolizumab, the results were similar. This combination aims to enhance the body's immune response to cancer cells. While some side effects can occur, they are usually manageable. These early findings provide promising evidence of safety for those considering joining the clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about GEN1042 because it offers a new approach to treating advanced cancers. Unlike traditional treatments that may target cancer cells directly, GEN1042 works by activating certain immune cells to better recognize and attack cancer cells, potentially leading to a more effective immune response. This mechanism of action is different from the standard chemotherapy or targeted therapy options, providing hope for improved outcomes. Additionally, the treatment is being tested both as a standalone therapy and in combination with other treatments, which could broaden its effectiveness across various cancer types.

What evidence suggests that GEN1042 might be an effective treatment for advanced cancers?

Research has shown that GEN1042, a special type of antibody, can help fight cancer by activating immune cells called CD40 and 4-1BB. This activation aids in developing cells crucial for initiating an immune response against cancer. Early studies found that GEN1042 can have anti-tumor effects in patients with advanced solid tumors. In this trial, some participants will receive GEN1042 as monotherapy, while others will receive it combined with another cancer drug, pembrolizumab, or with chemotherapy. This new approach remains under investigation, but initial results are promising, offering a more targeted and effective treatment for some cancers. ^{1 2 3 4 6}

Who Is on the Research Team?

Study Official

Principal Investigator

Genmab

Are You a Good Fit for This Trial?

Adults with certain advanced cancers (melanoma, NSCLC, CRC, HNSCC, PDAC) that have relapsed or are untreatable with no standard therapy available. Participants must be in good physical condition and have not had recent cancer treatments or surgeries. Those with autoimmune diseases, severe allergies to monoclonal antibodies, ongoing pneumonitis, or requiring high-dose steroids are excluded.

Inclusion Criteria

Measurable disease according to RECIST 1.1

My lung cancer is advanced, and I haven't had any cancer treatments yet.

I am part of the dose expansion phase of a combination therapy trial.

Exclusion Criteria

I still have side effects from past cancer treatments.

I haven't taken cancer drugs within the last 21 days or 5 half-lives before starting GEN1042.

I haven't had chemotherapy, biological therapy, or major surgery within the last 3 weeks or 5 half-lives of the drug before starting the trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation and Safety Run-in

Participants receive GEN1042 alone or in combination with pembrolizumab to determine safety and optimal dosing

3 weeks

Weekly visits

Dose Expansion

Participants receive GEN1042 at the determined dose to evaluate anti-tumor activity

Up to 2 years

Weekly visits initially, then every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• GEN1042

Trial Overview The trial is testing GEN1042's safety and effectiveness against tumors when used alone or combined with other cancer drugs like Paclitaxel and Pembrolizumab. It targets patients who've exhausted standard treatments for their metastatic solid tumors.

How Is the Trial Designed?

Group I: Monotherapy - Dose Escalation and Dose Expansion Parts Experimental Treatment 1 Intervention

Group II: Combination Therapy - Safety Run-in and Expansion Parts Experimental Treatment 9 Interventions

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

Bispecific and multispecific antibodies are emerging as powerful tools in treating autoimmune disorders, inflammatory diseases, and cancer by targeting multiple antigens or recruiting immune cells to enhance therapeutic effects.

Small antibody fragments, such as bispecific T-cell engagers, show promise for effectively targeting solid tumors due to their ability to penetrate tissues while retaining important immune functions, making them advantageous for cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fc Engineering for Developing Therapeutic Bispecific Antibodies and Novel Scaffolds. Liu, H., Saxena, A., Sidhu, SS., et al.[2019]

The study developed four types of bispecific antibodies (bsAbs) that effectively redirect T cells to target and kill Her2-expressing cancer cells, including those with low Her2 expression, in both lab tests and rodent models.

While varying the valency of the bsAbs did not impact their effectiveness, having an Fc domain increased their cytotoxic activity but also led to unintended T-cell activation, highlighting the need to balance efficacy and safety in therapeutic design.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiformat T-cell-engaging bispecific antibodies targeting human breast cancers. Cao, Y., Axup, JY., Ma, JS., et al.[2018]

The phase I/II trial of GEN1042, a bispecific antibody targeting CD40 and 4-1BB, indicates that the drug is well tolerated by patients with advanced solid tumors.

Preliminary results suggest that GEN1042 shows activity against these tumors, highlighting its potential as a new treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual-Targeting Approach for CD40 and 4-1BB. [2022]

DuoBody-CD40×4-1BB is a novel bispecific antibody that effectively enhances antitumor immunity by conditionally stimulating CD40 and 4-1BB, leading to improved dendritic cell maturation and T-cell activation in both laboratory assays and in patients with advanced solid tumors.

In a first-in-human clinical trial, DuoBody-CD40×4-1BB demonstrated significant immune modulation in patients, suggesting its potential as an effective treatment strategy for cancer when combined with PD-1 blocking antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DuoBody-CD40x4-1BB induces dendritic-cell maturation and enhances T-cell activation through conditional CD40 and 4-1BB agonist activity. Muik, A., Adams 3rd, HC., Gieseke, F., et al.[2022]

The bispecific antibody 1A10 effectively inhibits the growth of tumor cells that coexpress the human transferrin receptor (TfR) and the tumor-associated antigen gp40, demonstrating its potential as a targeted cancer therapy.

In mouse models, a single dose of 1A10 can maintain effective tumor concentrations for at least 7 days, leading to significant tumor growth inhibition, particularly in cells that express high levels of both target antigens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Binding characteristics and antitumor properties of 1A10 bispecific antibody recognizing gp40 and human transferrin receptor. Amoroso, AR., Clark, JI., Litwin, S., et al.[2007]

Bispecific antibodies targeting the EGF-receptor and immune effector cell receptors significantly enhance tumor cell killing compared to conventional monoclonal antibodies, indicating improved efficacy in treating renal cell carcinoma.

Using whole blood from patients treated with myeloid growth factors like G-CSF or GM-CSF, the bispecific antibodies showed the highest cytotoxicity, with granulocytes identified as the most effective immune cells in this process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical studies combining bispecific antibodies with cytokine-stimulated effector cells for immunotherapy of renal cell carcinoma. Elsässer, D., Stadick, H., Stark, S., et al.[2018]

Conventional type 1 dendritic cells are crucial for activating the immune response against tumors without causing the severe toxicities associated with CD40 agonists, which are primarily triggered by macrophages, platelets, and monocytes.

The development of bispecific antibodies that selectively target CD40 activation in dendritic cells shows promise for enhancing antitumor activity while significantly reducing the risk of dose-limiting toxicities, offering a safer alternative for cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific antibodies increase the therapeutic window of CD40 agonists through selective dendritic cell targeting. Salomon, R., Rotem, H., Katzenelenbogen, Y., et al.[2022]

The phase I trial of MEDI5752, a bispecific antibody that targets both PD-1 and CTLA4, shows that the drug is well tolerated by patients.

Preliminary results indicate that MEDI5752 is active in treating various tumor types, with durable responses observed, suggesting potential effectiveness in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

XFab-α4-1BB/CD40L is a bispecific antibody that effectively activates dendritic cells and promotes the proliferation of tumor-reactive T cells, leading to significant tumor regression in mouse models.

In non-human primates, XFab-α4-1BB/CD40L demonstrated a favorable safety profile with no liver toxicity observed at doses up to 51 mg/kg, indicating its potential for safe use in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

XFab-α4-1BB/CD40L fusion protein activates dendritic cells, improves expansion of antigen-specific T cells, and exhibits antitumour efficacy in multiple solid tumour models. Wang, B., Liu, Y., Yuan, R., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12272312/

CD40x4‐1BB (GEN1042/BNT312) Using a mPBPK/RO Model ... Trimer level outcomes were further assessed with clinical data for dose selection. An initial expansion dose of GEN1042 100 mg every 3 weeks was ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9189854/

DuoBody-CD40x4-1BB induces dendritic-cell maturation and ... DuoBody-CD40×4-1BB (GEN1042/BNT312) is a novel investigational Fc-inert bispecific antibody for dual targeting and conditional stimulation of CD40 and 4-1BB.

3. synapse.patsnap.com synapse.patsnap.com/drug/4a31841b469742a7bc5ee76098b1ae6b

GEN-1042 - Drug Targets, Indications, Patents These novel bsAbs hold the promise to further expand the range and strategies of cancer treatment, providing more precise and efficient therapeutic options.

4. clin.larvol.com clin.larvol.com/trial-detail/NCT04083599

GEN1042 Safety Trial and Anti-tumor Activity in ... First-in-human phase 1/2 trial to evaluate safety and initial clinical activity of DuoBody®-CD40x41BB (GEN1042) in patients with advanced solid tumors.

5. cell.com cell.com/trends/cancer/fulltext/S2405-8033(24)00142-0

Bispecific antibodies: advancing precision oncology Bispecific antibodies (bsAbs) are engineered molecules designed to target two different epitopes or antigens. The mechanism of action is ...

6. researchgate.net researchgate.net/publication/357151272_493_First-in-human_phase_12_trial_to_evaluate_the_safety_and_initial_clinical_activity_of_DuoBodyR-CD404-1BB_GEN1042_in_patients_with_advanced_solid_tumors

CD40×4–1BB (GEN1042) in patients with advanced solid ... Data presented with GEN1042 has demonstrated good tolerability and early signs of clinical activity [66,67]. ... ... This bispecific antibody ...