FOLFOX + Botensilimab + Balstilimab for Rectal Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Prior treatment, Autoimmune disease, 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)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 38

Duration: 16 weeks

26 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, if you are on corticosteroids or other immunosuppressive medications, you may need to stop them before starting the trial. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug combination FOLFOX + Botensilimab + Balstilimab for rectal cancer?

The research shows that FOLFOX, a part of the treatment, has demonstrated a survival benefit in metastatic colorectal cancer, which is similar to rectal cancer. This suggests that FOLFOX could be effective in improving survival in rectal cancer as well. ^{1 2 3 4 5}

How is the drug FOLFOX + Botensilimab + Balstilimab unique for rectal cancer treatment?

This treatment combines FOLFOX, a standard chemotherapy regimen, with two novel drugs, Botensilimab and Balstilimab, which are designed to enhance the immune system's ability to fight cancer. This combination aims to improve the effectiveness of treatment by using both traditional chemotherapy and new immunotherapy approaches. ^{6 7 8 9 10}

What is the purpose of this trial?

This phase II trial tests how well fluorouracil, oxaliplatin and leucovorin calcium (folinic acid) (FOLFOX) with botensilimab and balstilimab given before surgery (neoadjuvant) works in treating patients with rectal adenocarcinoma that has not spread to other parts of the body (localized). Currently, neoadjuvant therapy for rectal cancer includes chemotherapy and chemoradiation. Despite these aggressive treatments, only about half of patients achieve a complete clinical response. In fact, over half of rectal cancer patients go on to have surgery and often suffer post-surgery complications involving urine and bowel problems. Thus, there has been an increased focus on non-surgical treatments. Chemotherapy drugs, such as fluorouracil, oxaliplatin and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as botensilimab and balstilimab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving neoadjuvant FOLFOX with botensilimab and balstilimab may improve the rate of complete response and decrease the need for surgery and radiation therapy in patients with localized rectal adenocarcinoma.

Research Team

Marwan G Fakih

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for patients with localized rectal adenocarcinoma, which hasn't spread elsewhere. Participants should be candidates for neoadjuvant therapy before surgery and must not have received prior treatments that would conflict with the study drugs.

Inclusion Criteria

If unavailable, exceptions may be granted with study principal investigator (PI) approval

Hemoglobin ≥ 9g/dL

Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

Exclusion Criteria

I am not pregnant or breastfeeding.

Prior allergic reaction or hypersensitivity to any of the study drug components

Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive FOLFOX, botensilimab, and balstilimab intravenously in cycles every 14 days for up to 8 cycles

16 weeks

8 visits (in-person)

Extension

Participants with complete clinical response may continue to receive balstilimab alone for an additional 12 cycles

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Follow-up at 30 and 90 days, then every 3 months within 1 year, followed by every 6 months for up to 2 years

Treatment Details

Interventions

• Balstilimab
• Botensilimab
• FOLFOX

Trial Overview The trial tests a combination of chemotherapy (FOLFOX) and immunotherapy (botensilimab and balstilimab) given before surgery to see if it can improve complete response rates in rectal cancer, potentially reducing the need for surgery or radiation.

Participant Groups

Group I: Treatment (FOLFOX, botensilimab, balstilimab) Experimental Treatment 13 Interventions

Patients receive leucovorin calcium IV over 2 hours, oxaliplatin IV over 2 hours, and fluorouracil IV over 46 hours on day 1 of each cycle. Patients also receive botensilimab IV over 60 minutes on day 1 of cycles 1 and 4 and balstilimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients with complete clinical response may continue to receive balstilimab alone for an additional 12 cycles. Patients without complete clinical response may receive radiation therapy QD on weekdays and capecitabine PO BID concurrently on days of radiation therapy per standard of care. Additionally, patients undergo blood sample collection, biopsy with endoscopy exam, sigmoidoscopy, digital rectal exam, CT and MRI throughout the study.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase III study, both bevacizumab (BV) combined with irinotecan, fluorouracil, and leucovorin (IFL) and oxaliplatin with fluorouracil and leucovorin (FOLFOX) showed significant improvements in progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer, regardless of whether they responded to the initial treatment.

The study found that even nonresponders to initial therapy benefited from these superior treatments, indicating that tumor response is not necessary for patients to experience survival benefits from these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response-independent survival benefit in metastatic colorectal cancer: a comparative analysis of N9741 and AVF2107. Grothey, A., Hedrick, EE., Mass, RD., et al.[2022]

In a retrospective analysis of 25 patients with KRAS wild-type metastatic colorectal cancer who progressed after cetuximab treatment, panitumumab showed promising activity, with a median progression-free survival of 5 months and overall survival of 8 months.

Despite the previous treatment failure, 25% of patients experienced stable disease for at least 9 months, and the treatment was generally well-tolerated, with minimal severe side effects, indicating that panitumumab may be a viable option for patients seeking continued treatment without chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab after progression on cetuximab in KRAS wild-type metastatic colorectal cancer patients: a single institution experience. Marino, A., Caliolo, C., Sponziello, F., et al.[2018]

In a study of 43 patients with BRAF V600-mutant metastatic colorectal cancer, the combination of dabrafenib and trametinib showed activity, with 12% of patients achieving a partial response and one patient achieving a complete response lasting over 36 months.

All patients evaluated during treatment showed a significant reduction in phosphorylated ERK levels, indicating effective inhibition of the mitogen-activated protein kinase signaling pathway, although the response was less pronounced than in BRAF-mutant melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined BRAF and MEK Inhibition With Dabrafenib and Trametinib in BRAF V600-Mutant Colorectal Cancer. Corcoran, RB., Atreya, CE., Falchook, GS., et al.[2022]

In a study involving 1,186 patients with wild-type KRAS metastatic colorectal cancer, the combination of panitumumab and FOLFIRI significantly improved progression-free survival (PFS) compared to FOLFIRI alone, with a median PFS of 6.7 months versus 4.9 months.

While there was a trend towards improved overall survival (OS) with panitumumab-FOLFIRI (14.5 months vs. 12.5 months), it was not statistically significant; however, response rates increased dramatically from 10% to 36% with the combination treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final results from a randomized phase 3 study of FOLFIRI {+/-} panitumumab for second-line treatment of metastatic colorectal cancer. Peeters, M., Price, TJ., Cervantes, A., et al.[2022]

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]

References

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

Response-independent survival benefit in metastatic colorectal cancer: a comparative analysis of N9741 and AVF2107. [2022]

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

Panitumumab after progression on cetuximab in KRAS wild-type metastatic colorectal cancer patients: a single institution experience. [2018]

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

Combined BRAF and MEK Inhibition With Dabrafenib and Trametinib in BRAF V600-Mutant Colorectal Cancer. [2022]

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

Previous Bevacizumab and Efficacy of Later Anti-Epidermal Growth Factor Receptor Antibodies in Metastatic Colorectal Cancer: Results From a Large International Registry. [2019]

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

Final results from a randomized phase 3 study of FOLFIRI {+/-} panitumumab for second-line treatment of metastatic colorectal cancer. [2022]

6. Cyprus pubmed.ncbi.nlm.nih.gov

Safety and efficacy of FOLFIRI-bevacizumab for metastatic colorectal carcinoma as second line treatment. [2015]

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. New Zealand pubmed.ncbi.nlm.nih.gov

A randomized Phase II clinical study of combining panitumumab and bevacizumab, plus irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) compared with FOLFIRI alone as second-line treatment for patients with metastatic colorectal cancer and KRAS mutation. [2022]

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

Initial Panitumumab Plus Fluorouracil, Leucovorin, and Oxaliplatin or Plus Fluorouracil and Leucovorin in Elderly Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer: The PANDA Trial by the GONO Foundation. [2023]

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

A phase 3 trial evaluating panitumumab plus best supportive care vs best supportive care in chemorefractory wild-type KRAS or RAS metastatic colorectal cancer. [2018]