Aplitibart for Metastatic Colorectal Cancer

Recruiting at 69 trial locations

Overseen By Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1

Must not be taking: Liver toxicity agents, Anticancer agents

Disqualifiers: CNS metastases, Major surgery, others

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

Compensation: Varies

Number of Visits: Unknown

272 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called aplitibart with standard chemotherapy and another drug in patients with metastatic colorectal cancer that has come back or spread. The treatment works by killing cancer cells and cutting off their nutrient supply.

Will I have to stop taking my current medications?

The trial requires that you stop taking any anti-cancer agents and certain other medications before starting the study treatment. If you are on medications that cause liver toxicity or have recently used chemotherapy or other specific treatments, you may need to stop those as well.

What data supports the effectiveness of the drug Aplitibart + Chemotherapy for Colorectal Cancer?

Research shows that irinotecan, a component of the treatment, significantly prolongs survival in patients with metastatic colorectal cancer when combined with other drugs like 5-fluorouracil and leucovorin. This combination is considered a standard treatment and has shown promising results in improving patient outcomes. ^{1 2 3 4 5}

Is the combination of chemotherapy drugs with bevacizumab safe for treating colorectal cancer?

The combination of chemotherapy drugs like FOLFOXIRI or CAPOXIRI with bevacizumab has been studied for safety in treating colorectal cancer. Common side effects include diarrhea and neutropenia (low white blood cell count), but these are generally manageable. Overall, these combinations have shown an acceptable safety profile in patients with colorectal cancer. ^{6 7 8 9 10}

What makes the drug Aplitibart + Chemotherapy unique for colorectal cancer?

The combination of Aplitibart with chemotherapy for colorectal cancer is unique because it includes a mix of drugs like Azacitidine, Birinapant, and IGM-8444, which are not typically used together in standard treatments. This novel combination aims to target cancer cells more effectively by using different mechanisms of action, potentially offering a new approach for patients who may not respond to existing therapies. ^{9 11 12 13 14}

Research Team

Eric Humke, MD, PhD

Principal Investigator

IGM Biosciences

Eligibility Criteria

This trial is for adults with colorectal cancer that has returned or spread after treatment. Participants can have had prior treatments, must be able to perform light daily activities, and should not have been treated with irinotecan for their cancer.

Inclusion Criteria

Can you move around easily and do simple tasks like light housework or office work during the day?

Are you mobile and able to carry out light work throughout your day? (e.g. light house work or office work)

Has your colorectal cancer progressed within the last 6 months?

Exclusion Criteria

Have you ever received Irinotecan, (otherwise known as Camptosar and/or Onivyde) to treat your colorectal cancer?

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a Treatment

Participants receive aplitabart as a single agent or in combination with other agents in a dose-escalation and expansion stage

6 months

Regular visits at pre-defined intervals

Phase 1b Treatment

Colorectal participants receive aplitabart in combination with FOLFIRI and bevacizumab in an open-label, randomized study

36 months

Regular visits at pre-defined intervals

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Azacitidine
• Bevacizumab
• Birinapant
• Docetaxel
• FOLFIRI
• Gemcitabine
• IGM-8444
• Venetoclax

Trial Overview The study is examining the safety and effectiveness of aplitibart combined with FOLFIRI chemotherapy and bevacizumab in treating advanced colorectal cancer. It aims to find out if this new combination can help patients whose cancer has relapsed or spread.

Participant Groups

Group I: Ph1b: FOLFIRI + Bevacizumab Experimental Treatment 2 Interventions

Standard of Care FOLFIRI + bevacizumab will be administered intravenously

Group II: Ph1b: Aplitabart + FOLFIRI + Bevacizumab Experimental Treatment 3 Interventions

Aplitabart will be administered intravenously in combination with FOLFIRI + bevacizumab

Group III: Ph1a: Aplitabart Single Agent Alternate Dosing Escalation Experimental Treatment 1 Intervention

Aplitabart will be administered intravenously as a single agent on an alternate dosing schedule.

Group IV: Ph1a: Aplitabart + Venetoclax Escalation and Expansion Experimental Treatment 2 Interventions

Aplitabart will be administered intravenously in combination with Venetoclax.

Group V: Ph1a: Aplitabart + Venetoclax + Azacitidine Escalation and Expansion Experimental Treatment 3 Interventions

Aplitabart will be administered intravenously in combination with Venetoclax and Azacitidine.

Group VI: Ph1a: Aplitabart + FOLFIRI ± bevacizumab Escalation and Expansion Experimental Treatment 3 Interventions

Aplitabart will be administered intravenously in combination with FOLFIRI± bevacizumab.

Group VII: Ph1a: Aplitabart + Docetaxel + Gemcitabine Escalation and Expansion Experimental Treatment 3 Interventions

Aplitabart will be administered intravenously in combination with Docetaxel and Gemcitabine.

Group VIII: Ph1a: Aplitabart + Birinapant Escalation and Expansion Experimental Treatment 2 Interventions

Aplitabart will be administered intravenously in combination with Birinapant which will also be administered intravenously.

Azacitidine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

Lead Sponsor

Trials

1

Recruited

270+

IGM Biosciences, Inc.

Lead Sponsor

Trials

10

Recruited

520+

Lead Sponsor

Trials

1

Recruited

270+

Findings from Research

In a study of 94 patients aged 70 and older with advanced colorectal cancer, both CAPOX and CAPIRI treatments showed similar overall response rates (38% for CAPOX and 36% for CAPIRI), indicating comparable efficacy as first-line treatments.

CAPOX was better tolerated than CAPIRI, with fewer severe side effects such as diarrhea and neutropenia, suggesting it may be a safer option for elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine in combination with oxaliplatin or irinotecan in elderly patients with advanced colorectal cancer: results of a randomized phase II study. Rosati, G., Cordio, S., Bordonaro, R., et al.[2020]

Irinotecan has been shown to significantly prolong survival in patients with 5-FU-resistant colorectal cancer compared to best supportive care or 5-FU-based chemotherapy, based on Phase III studies.

Combining irinotecan with other treatments, such as raltitrexed or oral fluoropyrimidines, has shown promising results in terms of safety and efficacy, with response rates exceeding 30% and median survival benefits in various cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical advances with topoisomerase I inhibitors in gastrointestinal malignancies. Armand, JP., Cunningham, D., van Cutsem, E., et al.[2019]

Irinotecan has been established as a standard treatment for advanced/metastatic colorectal cancer, showing survival benefits over best supportive care and 5-fluorouracil (5-FU) without negatively affecting patients' quality of life.

Combining irinotecan with oral capecitabine has shown promising results in terms of efficacy and safety, offering a more convenient treatment option compared to traditional infused 5-FU, and represents a potential new standard for first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the use of irinotecan in colorectal cancer. Cunningham, D., Maroun, J., Vanhoefer, U., et al.[2019]

The combination of FOLFIRI and aflibercept was found to be active and tolerable in treating metastatic colorectal cancer (mCRC), with an objective response rate of 46.6% among 73 patients, indicating potential effectiveness in this patient population.

Despite its activity, the regimen did not surpass historical benchmarks for efficacy in chemotherapy-naive patients, with a 12-month progression-free survival rate of only 21.9% and a median overall survival of 20.9 months, suggesting that while it may help some patients, it may not be a significant improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMALTHEA: Prospective, Single-Arm Study of the Hellenic Cooperative Oncology Group (HeCOG) Evaluating Efficacy and Safety of First-Line FOLFIRI + Aflibercept for 6 Months Followed by Aflibercept Maintenance in Patients With Metastatic Colorectal Cancer. Pentheroudakis, G., Kotoula, V., Koliou, GA., et al.[2019]

The combination of FOLFOXIRI and bevacizumab demonstrated a promising progression-free survival (PFS) rate of 74% at 10 months in patients with unresectable metastatic colorectal cancer, based on a phase 2 study involving 57 patients.

The treatment was found to be safe, with no unexpected adverse events reported, although common serious side effects included neutropenia and hypertension, indicating that while effective, careful monitoring for these side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. Masi, G., Loupakis, F., Salvatore, L., et al.[2022]

The modified FOLFIRI regimen, which includes irinotecan, 5-fluorouracil, and a low dose of leucovorin, demonstrated a 47.8% overall response rate in 44 patients with recurrent or metastatic colorectal cancer, indicating its efficacy as a first-line treatment.

The treatment was well-tolerated, with mild and manageable toxicities; only a few patients experienced severe side effects, such as Grade 3/4 leukopenia and diarrhea, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan, continuous 5-fluorouracil, and low dose of leucovorin (modified FOLFIRI) as first line of therapy in recurrent or metastatic colorectal cancer. Lee, MA., Byun, JH., Shim, BY., et al.[2019]

A phase II study involving 43 patients with advanced gastrointestinal tumors showed that capecitabine combined with either irinotecan or oxaliplatin is effective in treating colorectal and other GI cancers, demonstrating significant clinical activity as both first-line and salvage therapy.

The combination therapies exhibited an excellent safety profile, with manageable grade 3/4 toxicities primarily limited to diarrhea, and no severe myelosuppression observed, indicating that these regimens are safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of capecitabine/irinotecan and capecitabine/oxaliplatin in advanced gastrointestinal cancers. Jordan, K., Kellner, O., Kegel, T., et al.[2019]

Irinotecan has shown significant activity against advanced colorectal cancer when combined with traditional chemotherapy agents like fluorouracil, leading to clinical responses including complete remissions in patients.

The combination therapies have acceptable toxicity profiles, with neutropenia and delayed diarrhea being the most common side effects, indicating that irinotecan could be a safe option for treatment, although further large-scale phase III studies are needed to confirm its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European experience with irinotecan plus fluorouracil/folinic acid or mitomycin. Khayat, D., Gil-Delgado, M., Antoine, EC., et al.[2018]

The evolution of chemotherapy for colorectal cancer has shifted from the single-agent use of 5-fluorouracil (5-FU) to more effective combination regimens that include irinotecan, oxaliplatin, and targeted agents like bevacizumab, significantly improving patient survival rates.

Combination therapies utilizing 5-FU as a base have been shown to enhance treatment outcomes, highlighting the importance of integrating newer drugs into established regimens for better management of colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current approaches to first-line treatment of advanced colorectal cancer. Goldberg, RM.[2019]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Irinotecan in the treatment of colorectal cancer. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Capecitabine in combination with oxaliplatin or irinotecan in elderly patients with advanced colorectal cancer: results of a randomized phase II study. [2020]

3. Netherlands pubmed.ncbi.nlm.nih.gov

First-line chemotherapy with raltitrexed in metastatic colorectal cancer: an Association des Gastro-entérologues Oncologues (AGEO) multicentre study. [2022]

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

Clinical advances with topoisomerase I inhibitors in gastrointestinal malignancies. [2019]

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

Optimizing the use of irinotecan in colorectal cancer. [2019]

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

AMALTHEA: Prospective, Single-Arm Study of the Hellenic Cooperative Oncology Group (HeCOG) Evaluating Efficacy and Safety of First-Line FOLFIRI + Aflibercept for 6 Months Followed by Aflibercept Maintenance in Patients With Metastatic Colorectal Cancer. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. [2022]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Irinotecan, continuous 5-fluorouracil, and low dose of leucovorin (modified FOLFIRI) as first line of therapy in recurrent or metastatic colorectal cancer. [2019]

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

Phase II trial of capecitabine/irinotecan and capecitabine/oxaliplatin in advanced gastrointestinal cancers. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Protocol of the QUATTRO-II study: a multicenter randomized phase II study comparing CAPOXIRI plus bevacizumab with FOLFOXIRI plus bevacizumab as a first-line treatment in patients with metastatic colorectal cancer. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Novel chemotherapeutic agents in colorectal cancer. [2018]

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

Biweekly Raltitrexed Combined With Irinotecan as Second-Line Therapy for Patients With Metastatic Colorectal Cancer: A Phase II Trial. [2022]

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

European experience with irinotecan plus fluorouracil/folinic acid or mitomycin. [2018]

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

Current approaches to first-line treatment of advanced colorectal cancer. [2019]