GEN1042 for Advanced Cancers

Recruiting at 78 trial locations

Overseen By Genmab Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Genmab

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

Compensation: Varies

Number of Visits: 3

1287 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called GEN1042 to see if it can help treat advanced cancer. It focuses on patients whose cancer has spread or is hard to treat. The goal is to find out if GEN1042 can safely reduce or stop tumor growth.

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.

What data supports the idea that GEN1042 for Advanced Cancers is an effective treatment?

The available research shows that GEN1042, a drug targeting CD40 and 4-1BB on immune cells, is well tolerated and active in patients with advanced solid tumors. This suggests it could be an effective treatment for these cancers. While other treatments like MEDI5752 also show promise, GEN1042 specifically enhances the body's immune response against tumors, which is a key factor in its effectiveness. ^{1 2 3 4 5}

What data supports the effectiveness of the drug GEN1042 for advanced cancers?

Preliminary findings from a trial suggest that GEN1042, which targets specific proteins on immune cells, is well tolerated and shows activity in patients with advanced solid tumors. Additionally, it enhances the immune system's ability to fight cancer by activating certain immune cells. ^{1 2 3 4 5}

What safety data is available for GEN1042 in treating advanced cancers?

Preliminary findings from a first-in-human phase I/II trial of GEN1042 suggest that the drug is well tolerated in patients with advanced solid tumors. Additionally, bispecific antibodies like GEN1042 have been designed to target CD40 activation preferentially to dendritic cells, which may offer a superior safety profile compared to traditional CD40 agonists, reducing dose-limiting toxicities. ^{1 2 6 7 8}

Is GEN1042 safe for humans?

Preliminary findings from a trial suggest that GEN1042 is well tolerated in patients with advanced solid tumors, indicating it may be generally safe for humans. ^{1 2 6 7 8}

Is the drug GEN1042 a promising treatment for advanced cancers?

Yes, GEN1042 is a promising drug for advanced cancers. It is a special type of antibody that targets two important proteins on immune cells, CD40 and 4-1BB, which helps the immune system fight cancer. Early studies show that it is well tolerated by patients and can activate the immune system to attack tumors effectively. ^{1 2 3 6 9}

What makes the drug GEN1042 unique for treating advanced cancers?

GEN1042 is a unique drug because it is a bispecific antibody that targets both CD40 and 4-1BB on immune cells, enhancing the body's immune response against tumors while minimizing the severe side effects often seen with other CD40-targeting treatments. ^{1 2 3 6 9}

Research Team

Study Official

Principal Investigator

Genmab

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. England 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. [2022]

3. Greece pubmed.ncbi.nlm.nih.gov

Preclinical studies combining bispecific antibodies with cytokine-stimulated effector cells for immunotherapy of renal cell carcinoma. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

5. Germany 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. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Bispecific antibodies increase the therapeutic window of CD40 agonists through selective dendritic cell targeting. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Fc Engineering for Developing Therapeutic Bispecific Antibodies and Novel Scaffolds. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Multiformat T-cell-engaging bispecific antibodies targeting human breast cancers. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Binding characteristics and antitumor properties of 1A10 bispecific antibody recognizing gp40 and human transferrin receptor. [2007]