GEN1055 + Pembrolizumab for Cancer

Not currently recruiting at 3 trial locations

Overseen By Genmab Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Genmab

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Uncontrolled hypertension, Autoimmune disease, Hepatitis, others

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

Compensation: Varies

Number of Visits: 24

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of a new antibody treatment, GEN1055, on certain cancers. Researchers aim to understand how GEN1055 works alone and in combination with another cancer drug, pembrolizumab (KEYTRUDA), and possibly chemotherapy. The trial seeks to determine the best doses and assess how well these combinations combat cancer. It is recruiting participants with advanced or metastatic solid tumors who have not responded to standard treatments. Participants will receive active treatment for up to 24 months, with regular site visits to monitor safety and effectiveness. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had certain cancer treatments within 4 weeks or certain systemic therapies within 5 half-lives of the drug before starting the trial. It's best to discuss your current medications with the trial team.

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

Previous studies have found GEN1055 to be safe when used alone. About 33% of patients experienced moderate side effects, and no treatment-related deaths occurred, suggesting the treatment is generally well-tolerated.

When combined with pembrolizumab, the safety outlook remains positive. Pembrolizumab, already approved for treating certain cancers, is known for not causing severe side effects that could affect surgery outcomes. So far, combining these two treatments has not revealed any unexpected safety issues.

The trial is in its early stages, focusing primarily on safety and determining the right doses. While some safety information is still being collected, current data suggests the treatment's side effects are manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about GEN1055 in combination with pembrolizumab for cancer because it represents a novel approach to treatment. While most cancer therapies focus on directly attacking cancer cells, GEN1055 is designed to boost the body's immune response, potentially enhancing the effectiveness of pembrolizumab, an established immunotherapy. By combining GEN1055 with pembrolizumab, there is hope to improve patient outcomes by making cancer cells more visible to the immune system. Additionally, this combination might offer a new option for patients who have not responded well to existing treatments like chemotherapy and other standard immunotherapies.

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

Research shows that pembrolizumab, an antibody used in this trial, effectively treats various cancers. It is approved for conditions such as non-small cell lung cancer and melanoma. Studies indicate that pembrolizumab, particularly when combined with chemotherapy, can significantly improve survival rates. In this trial, some participants will receive pembrolizumab with GEN1055, while others may receive GEN1055 alone or with both pembrolizumab and standard chemotherapy. GEN1055 is newer and has less data available, but it is being tested for safety and effectiveness as a promising cancer-fighting antibody. Researchers are studying the combination of GEN1055 and pembrolizumab to determine if they work better together. Early results are promising, but more research is needed to fully understand their benefits. ^{1 2 5 6 7}

Who Is on the Research Team?

Study Official

Principal Investigator

Genmab

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced solid tumors that have worsened after standard treatments or when no other treatment is likely to help. They should be relatively healthy otherwise, able to perform daily activities with ease (ECOG PS score of 0-1), and have measurable disease according to specific criteria.

Inclusion Criteria

I can provide scans showing my cancer's progress after the last treatment failed.

I am fully active or restricted in physically strenuous activity but can do light work.

My cancer can be measured by scans.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive GEN1055 as monotherapy or in combination with pembrolizumab to determine the recommended phase 2 dose and maximum tolerated dose

21 days per cycle

Weekly visits for the first 12 weeks, then every 3 weeks

Expansion

Participants receive GEN1055 at selected doses to evaluate safety, tolerability, and antitumor activity

Up to 24 months

Weekly visits for the first 12 weeks, then every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 39 months

What Are the Treatments Tested in This Trial?

Interventions

• GEN1055
• Pembrolizumab
• Standard Chemotherapy

Trial Overview The study tests the antibody GEN1055 alone and in combination with pembrolizumab, with or without standard chemotherapy. The first part determines safe doses; the second part evaluates how well these doses work against cancer. Treatment can last up to 24 months unless stopped earlier due to progression or side effects.

How Is the Trial Designed?

Group I: Expansion Experimental Treatment 3 Interventions

GEN1055 will be administered as monotherapy or in combination with pembrolizumab or in combination with pembrolizumab and standard chemotherapy in separate expansion cohorts, at a dose level selected from the Dose Escalation part.

Group II: Dose Escalation Experimental Treatment 2 Interventions

GEN1055 will be administered as monotherapy and in combination with a fixed dose of pembrolizumab.

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

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06391775

Study Details | NCT06391775 | Trial to Assess the Safety ... The goal of this trial is to learn about the antibody GEN1055 when it is used alone and when it is used together with another antibody cancer drug, ...

2. abbvieclinicaltrials.com abbvieclinicaltrials.com/study/?id=GCT1055-01

Trial to Assess the Safety and Preliminary Efficacy of ... The goal of this trial is to learn about the antibody GEN1055 when it is used alone and when it is used together with another antibody cancer drug.

3. clinicaltrials.eu clinicaltrials.eu/inn/gen1055/

Gen1055 – Application in Therapy and Current Clinical ... This medication is currently in the early stages of clinical trials, which means it's being tested to see how safe and effective it is for treating cancer ...

4. trial.medpath.com trial.medpath.com/news/f7fa6db86e0868ee/genmab-and-biontech-advance-two-phase-1-2-cancer-trials-testing-novel-antibody-therapies

Genmab and BioNTech Advance Two Phase 1/2 Cancer Trials ... Genmab and BioNTech are conducting two separate clinical trials evaluating novel antibody therapies for solid tumors, including GEN1055 monotherapy and ...

5. withpower.com withpower.com/trial/phase-2-neoplasms-3-2024-8e7d9

GEN1055 + Pembrolizumab for Cancer · Info for Participants Pembrolizumab has shown effectiveness in treating various cancers, including non-small cell lung cancer and melanoma. It has been approved by the FDA for ...

6. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effects-of-gen1055-alone-and-with-pembrolizumab-for-patients-with-malignant-solid-tumors/

Study on the Safety and Effects of GEN1055 Alone ... The purpose of the study is to evaluate the safety and preliminary effectiveness of GEN1055 in treating these tumors. Participants will ...

7. clin.larvol.com clin.larvol.com/trial-detail/NCT06391775

Trial to Assess the Safety and Preliminary Efficacy of ... Trial to Assess the Safety and Preliminary Efficacy of GEN1055 on Malignant Solid Tumors as Monotherapy and as Combination Therapy ... Outcome Measure ...