RO7122290 + Cibisatamab for Colorectal Cancer

No longer recruiting at 27 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 1

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments for colorectal cancer that has spread and hasn't responded to previous treatments. Participants will receive a mix of three drugs, including RO7122290 (an experimental treatment) and cibisatamab, to determine the optimal dose and assess the cancer's response. It targets individuals with a specific type of colorectal cancer that is stable and exhibits high levels of a protein called CEACAM5. Those with colorectal cancer that has progressed despite standard therapies may be suitable candidates. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

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

In earlier studies, RO7122290 has proven safe when used alone or with atezolizumab. These studies found that patients with certain solid tumors generally tolerated it well, with most side effects being manageable and not severe.

Research on cibisatamab, another part of this trial, also indicates safety for patients. Tested with and without atezolizumab, it was tolerated by patients with colorectal cancer unresponsive to previous treatments.

These findings suggest that both RO7122290 and cibisatamab have been safe for patients in past research. However, since this trial is in an early phase, more data is needed to fully understand their safety when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a fresh approach to tackling colorectal cancer. Unlike standard chemotherapy and targeted therapies like bevacizumab or cetuximab, this combination utilizes a novel mechanism involving RO7122290, which is designed to enhance the immune system's response against cancer cells. Cibisatamab is a bispecific antibody that targets the tumor while obinutuzumab is used as a pre-treatment to prepare the immune system, potentially improving the efficacy of the treatment. This innovative strategy aims to boost the body's own defenses to fight the cancer more effectively, which could lead to better outcomes for patients.

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

Research has shown that cibisatamab effectively targets cancer cells with high levels of a protein called CEA, commonly found in cancer. It enhances the body's immune response to attack the tumor. In lab studies, cibisatamab performed well, particularly when cancer cells exhibited high CEA levels. In this trial, participants will receive RO7122290 combined with cibisatamab and obinutuzumab pre-treatment. RO7122290, when used with other treatments like atezolizumab, has shown early promise in halting tumor growth and is considered safe for treating certain cancers. One study found that using RO7122290 and cibisatamab together resulted in an average survival time of 15.1 months for patients with colorectal cancer. This suggests these treatments could be very effective in managing this type of cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39858076

In Vitro Evaluation of the Safety and Efficacy ... Our results show that Cibisatamab effectively induces cell death in cancer spheroids with high CEA expression while being dose-dependent on target, off-tumor ...

2. nature.com nature.com/articles/s41467-024-48479-8

CEA-CD3 bispecific antibody cibisatamab with or without ... In nonclinical models, cibisatamab demonstrated the ability to increase T-cell infiltration in CEA-expressing tumours, thus converting non- ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03866239

NCT03866239 | A Phase Ib Study to Evaluate the Safety, ... A Phase Ib, open-label, multicenter, single-arm study designed to evaluate the safety, efficacy, pharmacokinetics, and immunogenicity of cibisatamab in ...

4. vhio.net vhio.net/2024/06/18/novel-t-cell-bispecific-antibody-shows-promise-in-retriggering-the-immune-response-to-combat-metastatic-colorectal-cancer/

Novel T-cell bispecific antibody. Metastatic colorectal cancer Cibisatamab-related grade ≥3 adverse events occurred in 36% of patients in S1 and in 49% of S2 patients. The overall response rate (ORR) was 4% ...

5. mdpi.com mdpi.com/2072-6694/17/2/291/review_report

Cancers | Free Full-Text | In Vitro Evaluation of the Safety ... We have revised the title of our study to: In vitro Evaluation of the Safety and Efficacy of Cibisatamab using Adult Stem Cell-derived Organoids and Colorectal ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11763756/

In Vitro Evaluation of the Safety and Efficacy of Cibisatamab ... This study introduces an advanced 3D assay using colorectal cancer spheroids and adult stem cell-derived, healthy human organoids to evaluate the efficacy and ...

7. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/crc/a-phase-ib-study-to-evaluate-the-safety--efficacy--and--82576.html

Clinical Trial – Colorectal Adenocarcinoma with High CEA ... The purpose of this clinical trial is to test the safety and effectiveness of cibisatamab when given with another drug called atezolizumab after pre ...