RO7122290 + Cibisatamab for Colorectal Cancer

Recruiting at 25 trial locations

Overseen By Reference Study ID Number: BP42675 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hoffmann-La Roche

Must not be taking: Anticoagulants, Immunosuppressants

Disqualifiers: CNS metastases, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 6

Duration: Up to 28 months

54 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug combination for a specific type of colorectal cancer that hasn't responded to previous treatments. It helps the immune system better recognize and attack cancer cells. The trial involves a combination of Avelumab and Cetuximab, which are being tested to enhance immune response against colorectal cancer cells.

Will I have to stop taking my current medications?

The trial requires that you stop taking any systemic anti-cancer therapy, including chemotherapy or hormonal therapy, at least 28 days before starting the study treatment. Additionally, you must stop taking systemic immunosuppressive medications at least 2 weeks before starting the study treatment.

What makes the drug combination RO7122290 + Cibisatamab unique for colorectal cancer?

The combination of RO7122290, Cibisatamab, and Obinutuzumab (Gazyva) is unique because it targets specific proteins on cancer cells, potentially offering a new approach for treating colorectal cancer compared to traditional chemotherapy. This combination may work differently by engaging the immune system to attack cancer cells more effectively. ^{1 2 3 4 5}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with metastatic colorectal cancer that's microsatellite-stable or MSI-low and has high CEACAM5 expression. Participants must have progressed after standard treatments, be in good physical condition (ECOG 0 or 1), have normal kidney function, adequate organ functions, a life expectancy of at least 12 weeks, and use effective contraception.

Inclusion Criteria

My condition worsened within 3 months after my last standard treatment.

I am fully active or restricted in physically strenuous activity but can do light work.

My cancer is a type of colon or rectal cancer confirmed by a lab test.

Exclusion Criteria

I need extra oxygen or have severe trouble breathing due to my advanced cancer.

Known hypersensitivity to Chinese hamster ovary cell products

I need procedures to remove fluid from around my lungs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Obinutuzumab Pre-Treatment

Participants receive obinutuzumab as a pretreatment to prepare for the main treatment phase

1 week

2 visits (in-person)

Treatment

Participants receive RO7122290 in combination with cibisatamab every 3 weeks, following obinutuzumab pretreatment

Up to 28 months

Weekly visits during initial cycles, then every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days

1 visit (in-person)

Treatment Details

Interventions

• Cibisatamab
• Obinutuzumab
• RO7122290

Trial Overview The study tests the combination of RO7122290 and Cibisatamab following Obinutuzumab pretreatment to find the safest dose with potential anti-tumor effects. It's an early-phase trial involving participants who receive these drugs on weekly or every three-week schedules to assess tolerability and preliminary effectiveness.

Participant Groups

Group I: Part II: Dose-expansion of RO7122290 Experimental Treatment 3 Interventions

Part II of this study will evaluate selected dose levels of RO7122290 from Part I (a QW RO712290 administration in combination with a Q3W cibisatamab administration with obinutuzumab pre-treatment) in a Q3W regimen in combination with a Q3W cibisatamab administration with obinutuzumab pre-treatment.

Group II: Part I: Dose-escalation of RO7122290 Experimental Treatment 3 Interventions

The dose-escalation of RO7122290 will use a QW dosing schedule of RO7122290 in combination with a Q3W dosing interval for cibisatamab with obinutuzumab pre-treatment. The starting dose for RO7122290 will be 35 mg, which represents the human equivalent dose for the minimal pharmacologically active dose (1 mg/kg) in mice.

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Findings from Research

In a phase II trial involving 53 patients with advanced wild-type K-RAS colorectal cancer, the combination of panitumumab and irinotecan every 3 weeks demonstrated safety and efficacy, with 23% of patients achieving partial responses and 41% achieving disease stabilization.

The treatment resulted in a median progression-free survival of 4.5 months and an overall survival of 15.1 months, with skin toxicity being significantly associated with clinical response, indicating that monitoring for skin reactions could be important in treatment evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab and irinotecan every 3 weeks is an active and convenient regimen for second-line treatment of patients with wild-type K-RAS metastatic colorectal cancer. Carrato, A., Gómez, A., Escudero, P., et al.[2021]

In a phase II study involving 99 patients with wild-type KRAS colorectal cancer, the biweekly combination of cetuximab and FOLFOX-4 achieved an overall response rate (ORR) of 60.6%, indicating significant efficacy as a first-line treatment.

The safety profile was consistent with previous studies, with common grade 3-4 toxicities including neutropenia (32.3%) and acne-like rash (15.2%), suggesting that the biweekly regimen is both effective and manageable for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biweekly cetuximab in combination with FOLFOX-4 in the first-line treatment of wild-type KRAS metastatic colorectal cancer: final results of a phase II, open-label, clinical trial (OPTIMIX-ACROSS Study). Fernandez-Plana, J., Pericay, C., Quintero, G., et al.[2023]

In a phase 2 study involving 148 patients with metastatic colorectal cancer, panitumumab demonstrated a 9% overall response rate and a median progression-free survival of 14 weeks, indicating its efficacy as a treatment option for patients who had previously failed other therapies.

Panitumumab was generally well tolerated, with manageable side effects; 95% of patients experienced skin toxicity, but only 5% had severe reactions, suggesting that while dermatologic issues are common, they are not typically severe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. Hecht, JR., Patnaik, A., Berlin, J., et al.[2018]

In the phase I/II KRYSTAL-1 trial, the KRASG12C inhibitor adagrasib showed a high disease control rate of 87% in patients with metastatic colorectal cancer when used alone, with a progression-free survival of 5.6 months.

When adagrasib was combined with the EGFR inhibitor cetuximab, the disease control rate improved to 100%, indicating a potentially more effective treatment strategy, although progression-free survival data for this combination is still being evaluated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adagrasib Data Create Buzz at ESMO. [2022]

In a phase Ib study involving 6 Japanese patients with metastatic colorectal carcinoma, the combination of ramucirumab and FOLFIRI was found to be well-tolerated, with only one patient experiencing a dose-limiting toxicity.

While all patients had at least one grade 3 or higher adverse event, there were no serious adverse events or deaths, suggesting that this treatment combination is relatively safe for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Pharmacokinetics of Second-line Ramucirumab plus FOLFIRI in Japanese Patients with Metastatic Colorectal Carcinoma. Yoshino, T., Yamazaki, K., Gotoh, M., et al.[2023]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Panitumumab and irinotecan every 3 weeks is an active and convenient regimen for second-line treatment of patients with wild-type K-RAS metastatic colorectal cancer. [2021]

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

Biweekly cetuximab in combination with FOLFOX-4 in the first-line treatment of wild-type KRAS metastatic colorectal cancer: final results of a phase II, open-label, clinical trial (OPTIMIX-ACROSS Study). [2023]

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

Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. [2018]

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

Adagrasib Data Create Buzz at ESMO. [2022]

5. Greece pubmed.ncbi.nlm.nih.gov

Safety and Pharmacokinetics of Second-line Ramucirumab plus FOLFIRI in Japanese Patients with Metastatic Colorectal Carcinoma. [2023]