GEN1046 for Cancer

Recruiting at 57 trial locations

Overseen By Genmab Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Genmab

Disqualifiers: Uncontrolled illness, Autoimmune disease, Heart failure, others

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

Compensation: Varies

Number of Visits: 3

429 Participants Needed

Trial Summary

What is the purpose of this trial?

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 with standard of care treatment (docetaxel) or another antibody cancer drug, pembrolizumab (with or without chemotherapy), for treatment of patients with certain types of cancer. All subjects will receive active drug; no one will receive placebo. This trial has 2 parts. The purpose of the first part is to find out if acasunlimab is safe and to find out the best doses of acasunlimab to use. The purpose of the second part is to give acasunlimab to more subjects to see how well the doses of acasunlimab selected in the first part work against cancer when given alone and how well they work when given with pembrolizumab (with or without other chemotherapy) or docetaxel. Trial details include: * The average trial duration for an individual subject will be about 74 weeks. * The average treatment duration for an individual subject will be about 21 weeks. * The visit frequency will be weekly at first and lessening over time until visits are only once every 3 weeks.

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.

What data supports the effectiveness of the drug GEN1046 for cancer?

Research on precision medicine, which involves tailoring treatments based on genetic profiles, shows that patients with specific genetic alterations can benefit from targeted therapies. In one study, patients with single pathway alterations who received matched therapies had a clinical benefit rate of 66.7%, suggesting that treatments like GEN1046, which may be designed for specific genetic targets, could be effective for certain cancer patients. ^{1 2 3 4 5}

What safety data exists for PD-1/PD-L1 inhibitors in cancer treatment?

PD-1/PD-L1 inhibitors, used in cancer treatment, can cause immune-related side effects like skin rash, itching, and fatigue. These side effects are generally manageable and may be associated with better treatment outcomes. ^{6 7 8 9 10}

Research Team

Study Official

Principal Investigator

Genmab

Eligibility Criteria

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.

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.

Timeline

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

Treatment Details

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.

Participant Groups

Group I: Expansion Experimental Treatment 4 Interventions

Acasunlimab will be administered as monotherapy or in combination with either docetaxel, pembrolizumab, or pembrolizumab + standard chemotherapy in separate expansion cohorts.

Group II: Dose Escalation Experimental Treatment 1 Intervention

Acasunlimab will be administered as monotherapy.

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

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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 study of 581 cancer patients treated with PD-1/PD-L1 inhibitors, 20% experienced endocrine adverse events (AEs), with pembrolizumab showing a significantly higher incidence of 38.5%.

Patients who developed endocrine AEs had better overall response rates (33.3% vs. 23.1%) and disease control rates (91.1% vs. 79.1%), suggesting that these AEs may be associated with a more favorable treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-world retrospective study of incidence and associated factors of endocrine adverse events related to PD-1/PD-L1 inhibitors. Wang, Z., Hu, C., Zhang, A., et al.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

The identification of driver mutations in tumors has led to the rise of personalized medicine in cancer treatment, allowing for targeted therapies like the BRAF inhibitor vemurafenib, which was approved for metastatic melanoma in 2012.

While targeted treatments are generally well-tolerated, they come with a new range of side effects that healthcare providers must understand and manage to ensure optimal patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of systemic oncological therapies in dermatology. Zimmer, L., Vaubel, J., Livingstone, E., et al.[2012]

References

1. England pubmed.ncbi.nlm.nih.gov

Precision medicine: preliminary results from the Initiative for Molecular Profiling and Advanced Cancer Therapy 2 (IMPACT2) study. [2021]

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

Clinical benefit of a precision medicine based approach for guiding treatment of refractory cancers. [2022]

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

Symptoms and Health-Related Quality of Life in Patients Receiving Cancer Therapy Matched to Genomic Profiles. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Case series of outcomes in advanced cancer patients with single pathway alterations receiving N-of-One therapies. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Characteristics and outcomes of patients with RET-fusion positive non-small lung cancer in real-world practice in the United States. [2023]

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

Association between immune-related adverse events and efficacy of PD-1 inhibitors in Chinese patients with advanced melanoma. [2021]

7. China pubmed.ncbi.nlm.nih.gov

A real-world retrospective study of incidence and associated factors of endocrine adverse events related to PD-1/PD-L1 inhibitors. [2023]

8. England pubmed.ncbi.nlm.nih.gov

PharmacoDB 2.0: improving scalability and transparency of in vitro pharmacogenomics analysis. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

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. [2021]

10. Germany pubmed.ncbi.nlm.nih.gov

Side effects of systemic oncological therapies in dermatology. [2012]