ATP128 + VSV-GP128 + BI 754091 for Colorectal Cancer

(KISIMA-01 Trial)

Not currently recruiting at 12 trial locations

Overseen By Ute Klinkhardt, PhD, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Amal Therapeutics

Must not be taking: Checkpoint inhibitors, Immunotherapy

Disqualifiers: Autoimmune disease, Active infection, CNS metastasis, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4.5 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and tolerability of a new treatment approach for advanced colorectal cancer that has not responded well to other treatments. The study explores the use of ATP128, a vaccine designed to boost the immune system, either alone or combined with another drug, BI 754091, which helps the body’s immune system fight cancer. Some patients will also receive VSV-GP128, a special virus designed to work with ATP128. The trial seeks participants with stage IV colorectal cancer who have not responded to standard treatments or have specific characteristics like stable disease or limited liver involvement. 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 treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must not have had certain treatments like monoclonal antibodies or chemotherapy within a specific time before starting the trial. It's best to discuss your current medications with the trial team to ensure they don't conflict with the study requirements.

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

Research shows that ATP128, combined with BI 754091 (a PD-1 inhibitor), is being tested for safety and tolerability in treating colorectal cancer. ATP128 is a vaccine designed to enhance the body's ability to fight cancer cells, while BI 754091 is a medicine that aids the immune system in attacking cancer.

Early results suggest that this combination is generally well-tolerated. Some participants have experienced mild side effects, such as tiredness or headaches, which are common in many treatments. So far, no major safety concerns have been reported.

Another component of the treatment, VSV-GP128, is also under investigation. This virus-based therapy aims to boost the body's immune response against cancer. Early studies suggest it is well-tolerated, with similar mild side effects.

As this research is in the early stages, ongoing studies are crucial to confirm safety and understand any long-term effects. Participants in this trial provide researchers with essential data about these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for colorectal cancer because they introduce innovative approaches beyond the current standard of care, which typically includes chemotherapy, targeted therapy, and immunotherapy. ATP128 is a cancer vaccine designed to stimulate the immune system to specifically attack colorectal cancer cells. VSV-GP128 is a viral vector therapy that uses a modified virus to deliver cancer-fighting agents directly into tumor cells, potentially enhancing the immune response. Lastly, BI 754091 is an immune checkpoint inhibitor that may help the body’s immune system to better recognize and combat cancer cells. These unique mechanisms of action offer promising new strategies for tackling colorectal cancer, especially for patients who have not responded well to existing treatments.

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

This trial will evaluate the combination of ATP128, VSV-GP128, and BI 754091 in various cohorts of patients with advanced colorectal cancer. Research has shown that ATP128, particularly when combined with VSV-GP128 and BI 754091, might enhance the immune system's ability to fight cancer cells. This combination aims to help the body recognize and attack cancer, differing from many traditional treatments. Early results indicate that adding BI 754091, which aids the immune system by blocking a protein called PD-1, may benefit some colorectal cancer patients who have not responded to other treatments. VSV-GP128 is used to boost the immune response, potentially increasing the treatment's effectiveness. Although this research remains in the early stages, these new methods offer hope, especially for individuals with advanced colorectal cancer who haven't found success with standard treatments. ^{2 3 4 5 6}

Who Is on the Research Team?

Scott Kopetz

Principal Investigator

MD Anderson

Are You a Good Fit for This Trial?

Adults with stage IV colorectal cancer who have failed standard therapies or are in stable condition after first-line treatment. They must be able to undergo biopsies, not pregnant or breastfeeding, willing to use contraception, and without certain health conditions like autoimmune diseases, active infections, or heart issues.

Inclusion Criteria

I have a liver lesion that can be biopsied multiple times.

I can take care of myself and am up and about more than half of my waking hours.

I have at least one tumor that can be measured on a scan.

Exclusion Criteria

I have or had hepatitis B or C.

My heart health does not meet the specific criteria listed, including issues with my heart's rhythm or a low ejection fraction.

I am not allergic to any of the drugs or their components used in this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ATP128 alone or in combination with BI 754091 and VSV-GP128, depending on cohort assignment

4.5 months

Regular visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Periodic visits for monitoring and assessments

Long-term follow-up

Participants are monitored for long-term outcomes such as progression-free survival and overall response

1 year

What Are the Treatments Tested in This Trial?

Interventions

• ATP128
• BI 754091
• VSV-GP128

Trial Overview The trial is testing ATP128 alone or with BI 754091 (Ezabenlimab), and a prime-boost regimen of ATP128 + VSV-GP128 with BI 754091. It's for patients whose cancers haven't responded well to PD-1 blockade treatments.

How Is the Trial Designed?

Group I: Cohort 4b Experimental Treatment 3 Interventions

15 patients with stage IV MSS/MMRp CRC with liver-limited disease

Group II: Cohort 4a Experimental Treatment 3 Interventions

24 patients with stage IV MSS/MMRp CRC in SD or PR after first line of SoC

Group III: Cohort 3 Experimental Treatment 3 Interventions

6 patients with stage IV MSS/MMRp CRC in SD or PR after first line of SoC

Group IV: Cohort 2c Experimental Treatment 2 Interventions

19 patients with stage IV MSS/MMRp CRC in SD or PR after first line of SoC

Group V: Cohort 2b Experimental Treatment 2 Interventions

15 patients with stage IV MSS/MMRp CRC with liver-limited disease

Group VI: Cohort 2a Experimental Treatment 2 Interventions

5 patients with stage IV MSS/MMRp CRC in SD or PR after first line of SoC

Group VII: Cohort 1b Experimental Treatment 2 Interventions

6 patients with stage IV MSS/MMRp CRC in SD or PR after first line of SoC

Group VIII: Cohort 1a Experimental Treatment 1 Intervention

6 patients with stage IV CRC who failed SoC therapies

Who Is Running the Clinical Trial?

Amal Therapeutics

Lead Sponsor

Trials

2

Recruited

180+

Boehringer Ingelheim

Industry Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

Adjuvant therapy using 5-fluorouracil and levamisole for node-positive colon cancer, and chemoradiotherapy with 5-fluorouracil and high-dose radiotherapy for stage II or III rectal cancer, significantly reduces recurrence and mortality, improving overall survival by over 30%.

Ongoing trials are exploring various combinations and durations of chemotherapy and radiotherapy, as well as the potential of aspirin for colon cancer prevention, indicating a shift towards more personalized and effective treatment strategies for colorectal adenocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant treatment of colorectal adenocarcinoma. Steele, G., Posner, MR.[2018]

Citations

1. humanforschung-schweiz.ch humanforschung-schweiz.ch/en/trial-search/study-detail/53236/translate/en/?cHash=f9e899e196eb01c354757a5731769e97

A phase Ib study evaluating ATP128, VSV-GP128, and BI ... This phase Ib study aims to evaluate the safety and tolerability as well as the efficacy of a therapeutic vaccine called ATP128 administered ...

2. cancer.gov cancer.gov/clinicaltrials/NCI-2019-07330

Phase 1b Study to Evaluate ATP128, VSV-GP128 and BI ... This is a multi-center, non-randomised Phase 1b study to evaluate the safety and tolerability of ATP128 alone or in combination with BI 754091.

3. medinfo.boehringer-ingelheim.com medinfo.boehringer-ingelheim.com/us/sites/default/files/2022-11/kisima-01%20fih%20trial%20of%20atp128vsv-gp128%20vaccine%20with%20ezabenlimab%20%28bi%20754091%29%20in%20stage%20iv%20crc.pdf

KISIMA-01 Blood and tissue samples are collected before, during and after ATP128/VSV-. GP128 treatment to monitor the induction of a tumor associated antigen-specific ...

4. withpower.com withpower.com/trial/phase-2-rectal-neoplasms-6-2019-199bc

ATP128 + VSV-GP128 + BI 754091 for Colorectal Cancer This combination aims to stimulate a strong and lasting immune attack on cancer cells, which is different from traditional treatments that may not engage the ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04046445/phase-1b-study-to-evaluate-atp128-vsv-gp128-and-bi-754091-in-patients-with-stage-iv-colorectal-cancer?mp=aa...&page=34&state=CA&city=Los%20Angeles

Phase 1b Study to Evaluate ATP128, VSV-GP128 and BI ... Patients in Cohort 1a will receive ATP128 as single agent. Patients in Cohorts 1b, 2a, 2b, 2c will receive ATP128 in combination with BI 754091.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04046445?cond=rectum+cancer&aggFilters=status%3A

Phase 1b Study to Evaluate ATP128, VSV-GP128 and BI 754091 ... A type of intervention model describing a clinical trial in which groups of participants receive one of several combinations of interventions. For example, two- ...