ATP128 + VSV-GP128 + BI 754091 for Colorectal Cancer

(KISIMA-01 Trial)

Recruiting at 11 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

96 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug ATP128 + VSV-GP128 + BI 754091 for colorectal cancer?

The research highlights the effectiveness of targeted therapies like anti-EGFR and anti-VEGF in colorectal cancer, which are similar to the components in ATP128 + VSV-GP128 + BI 754091. These therapies have shown promise in improving outcomes by targeting specific cancer growth pathways. ^{1 2 3 4 5}

What makes the ATP128 + VSV-GP128 + BI 754091 treatment unique for colorectal cancer?

This treatment is unique because it combines a cancer vaccine (ATP128), an oncolytic virus (VSV-GP128), and an immune checkpoint inhibitor (BI 754091) to enhance the body's immune response against 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 immune system as effectively. ^{6 7 8 9 10}

What is the purpose of this trial?

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 and of heterologous prime-boost ATP128 + VSV-GP128 in combination with BI 754091. ATP128 is a self-adjuvanted chimeric recombinant protein vaccine being developed in combination with programmed cell death 1 (PD-1) blockade for the treatment of microsatellite stable (MSS) patients not responding to PD-1 blockade. The PD-1 inhibitor being tested with ATP128 is the BI 754091 (Ezabenlimab) compound which belongs to the human immunoglobulin G4 (IgG4) subclass of antibodies. VSV-GP is a recombinant chimeric vesicular stomatitis virus (VSV, Indiana strain Rhabdoviridae) which carries the envelope glycoprotein (GP) of the visceral non neurotropic WE-HPI strain of the Lymphocytic choriomeningitis virus (LCMV, Arenaviridae) instead of the native VSV glycoprotein (G) and is developed as integral part of the prime-boost regimen together with ATP128. The Sponsor plans to enrol 96 patients with histologically or cytologically confirmed stage IV colorectal cancer coming form three different patient populations: * Cohort 1a: 6 patients with stage IV colorectal cancer (CRC) having failed standard of care (SoC) therapies * Cohorts 1b, 2a, 2c: 30 patients with stage IV microsatellite stable/mismatch repair-proficient (MSS/MMRp) CRC being in stable disease (SD) or partial response (PR) after first line of SoC (4-6 months duration at minimum) * Cohorts 2b, 4b: 30 patients with stage IV MSS/MMRp liver-limited disease Patients eligible for this study will be enrolled in one of the 8 cohorts depending on their disease: * 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 * Patients in Cohorts 3, 4a, 4b will receive ATP128 and VSV-GP128 in combination with BI 754091

Research Team

Scott Kopetz

Principal Investigator

MD Anderson

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

Opportunities for newer agents in combination with oxaliplatin. [2019]

2. Greece pubmed.ncbi.nlm.nih.gov

ATP11A is a novel predictive marker for metachronous metastasis of colorectal cancer. [2019]

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

Targeted therapy in rectal cancer. [2021]

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

Adjuvant treatment of colorectal adenocarcinoma. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Increased ATP2A1 Predicts Poor Prognosis in Patients With Colorectal Carcinoma. [2022]

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

A novel vaccinia virus enhances anti-tumor efficacy and promotes a long-term anti-tumor response in a murine model of colorectal cancer. [2022]

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

Bispecific T cell engagers and their synergistic tumor immunotherapy with oncolytic viruses. [2023]

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

Potent and specific antitumor effect for colorectal cancer by CEA and Rb double regulated oncolytic adenovirus harboring ST13 gene. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Immunotherapy based on bispecific T-cell engager with hIgG1 Fc sequence as a new therapeutic strategy in multiple myeloma. [2018]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Oncolytic virus driven T-cell-based combination immunotherapy platform for colorectal cancer. [2022]