CRB-601 Combination Therapy for Cancer

Recruiting at 25 trial locations

Overseen By Ian Hodgson, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Corbus Pharmaceuticals Inc.

Disqualifiers: Cardiovascular events, Liver disease, Autoimmune, others

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

Compensation: Varies

Number of Visits: 6

156 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new cancer treatment called CRB-601 to determine its safety and effectiveness when combined with immunotherapy, specifically an anti-PD-1 monoclonal antibody, for individuals with advanced solid tumors. The researchers aim to find the right dose of CRB-601 and assess its effectiveness in treating cancer by targeting a specific protein present in some tumors. Participants will receive the treatment every two weeks and undergo regular scans to monitor their cancer. This trial suits those with solid tumors that no longer respond to other treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research has shown that CRB-601 is likely safe. Early results suggest it is well tolerated when used alone. In studies, CRB-601 has demonstrated a good safety record, with most side effects being manageable. When combined with anti-PD-1 therapy, it remains promising. The combination is generally well tolerated, and side effects are manageable. Participants in studies have not reported any unexpected severe reactions. Thus far, CRB-601 appears safe for use in humans, either alone or with other treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for cancer, like chemotherapy and radiation, aim to kill cancer cells but can also harm healthy cells, leading to side effects. CRB-601 stands out because it targets cancer cells more precisely by combining with anti-PD(L)-1 therapy, which helps the immune system recognize and attack cancer cells. Researchers are excited because CRB-601, when combined with this immune therapy, could enhance the body's natural defenses against cancer while potentially reducing side effects. This combination approach could offer a more effective and targeted treatment option for patients.

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

Research has shown that CRB-601, one of the treatments in this trial, has shown promise in early studies when used alone. It can significantly slow tumor growth and reduce TGFβ-1 signaling, a harmful process in cancer, thereby slowing tumor progression. In this trial, some participants will receive CRB-601 combined with anti-PD-1 therapy. This combination can enhance the body's immune response, increasing the effectiveness of the existing treatment. Early research suggests that this combination improves the effectiveness of anti-PD-1 therapy. Overall, these initial findings indicate that CRB-601 could be a valuable addition to cancer treatment, especially for those with limited options. ^{1 3 6 7 8}

Who Is on the Research Team?

Jeff Clarke, MD

Principal Investigator

Duke University, NC, USA

Dominic Smethurst, MD

Principal Investigator

Corbus Pharmaceuticals Inc.

Christian Ottensmeier, MD

Principal Investigator

Liverpool University, UK

Are You a Good Fit for This Trial?

This trial is for patients with advanced solid tumors who have tried all other treatments. It's aimed at those whose cancers express a specific protein, avb8 integrin. Participants will receive the experimental drug CRB-601, alone or with immunotherapy and targeted radiotherapy.

Inclusion Criteria

Measurable disease on imaging as assessed by RECIST 1.1

My physical ability is limited but I can still take care of myself.

Life expectancy of more than 12 weeks

Exclusion Criteria

Other conditions that in the opinion of the Investigator would compromise the outcomes of the study

Systemic autoimmune disease

I have not had interstitial lung disease in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part A: Dose Escalation

Evaluate the safety, tolerability, and determine the MTD of CRB-601 administered as monotherapy

28 days per cycle

Visits every 2 weeks

Part B: Combination Safety Lead-in and Signal Seeking

Assess the safety and tolerability of CRB-601 combined with anti-PD(L)-1 therapy, with or without SBRT

6 months

Visits every 2 weeks

Part C: Dose Optimization

Determine the recommended Phase 2 dose by evaluating the efficacy of CRB-601 in combination with anti-PD(L)-1, with or without SBRT

6 months

Visits every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Anti-PD-1 monoclonal antibody
• CRB-601
• Immune-priming single lesion SBRT

Trial Overview Researchers are testing CRB-601, an antibody targeting avb8 integrin in cancer cells, combined with anti-PD-1 immunotherapy and focused radiotherapy. They want to find the right dose of CRB-601 and see if it's safe and effective when used with these standard treatments.

How Is the Trial Designed?

Group I: Part C - Low dose CRB-601 in combination with anti-PD(L)-1 Experimental Treatment 2 Interventions

Participants will receive a low dose of CRB-601 (defined in Part A \&B) in combination with standard of care dose of anti-PD(L)-1 therapy.

Group II: Part C - High dose CRB-601 in combination with anti-PD(L)-1 Experimental Treatment 2 Interventions

Participants will receive a high dose of CRB-601 (defined in Part A \&B) in combination with standard of care dose of anti-PD(L)-1 therapy.

Group III: Part B/Expansion: Dose level (defined in Part B/ Safety Le) CRB-601 in combination with anti-PD(L)-1 Experimental Treatment 2 Interventions

Dose (defined in Part B/ Safety Lead-In) or CRB-601 administered intravenously in combination with anti-PD(L)-1 therapy dosed per label.

Group IV: Part B/Cohort 2: Dose level (high) CRB-601 in combination with anti-PD(L)-1 Experimental Treatment 2 Interventions

High dose CRB-601 (defined in Part A) of CRB-601 administered intravenously in combination with anti-PD(L)-1 therapy dosed per label.

Group V: Part B/Cohort 1: Dose level (low) CRB-601 in combination with anti-PD(L)-1 Experimental Treatment 2 Interventions

Dose (defined in Part A) of CRB-601 administered intravenously in combination with anti-PD(L)-1 therapy dosed as per label.

Group VI: Part A: Dose 3 of CRB-601 monotherapy Experimental Treatment 1 Intervention

Dose 3 of CRB-601 (30mg/Kg) administered intravenously every two weeks

Group VII: Part A: Dose 2 of CRB-601 monotherapy Experimental Treatment 1 Intervention

Dose 2 of CRB-601 (10mg/Kg) administered intravenously every two weeks

Group VIII: Part A: Dose 1 CRB-601 monotherapy Experimental Treatment 1 Intervention

Dose 1 of CRB-601 (3mg/Kg) administered intravenously every two weeks

Who Is Running the Clinical Trial?

Corbus Pharmaceuticals Inc.

Lead Sponsor

Trials

9

Recruited

1,800+

Citations

1. ir.corbuspharma.com ir.corbuspharma.com/news-events/press-releases/detail/397/corbus-pharmaceuticals-presents-results-of-two-pre-clinical-studies-on-itsanti-v8-monoclonal-antibody-crb-601-at-the-2023-sitc-annual-meeting

Corbus Pharmaceuticals Presents Results of Two Pre ... CRB-601 demonstrated immunomodulatory effects as reflected in changes in cytotoxic CD8+ T cell population and gene expression in the TME.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06603844?term=Corbus%20Pharmaceuticals&rank=3

First-in-human Study of CRB-601-01 to Treat Patients With ... The purpose of this study is to determine the safety, blood concentrations and treatment effect of CRB-601 in combination with immunotherapy in patients who ...

3. jitc.bmj.com jitc.bmj.com/content/13/Suppl_2/A662

582 First-in-human phase 1/2 study of the integrin αvβ8 ... Conclusions Early phase 1/2 results suggest that CRB-601 is well tolerated with a favorable safety profile. These initial results suggest that ...

4. ir.corbuspharma.com ir.corbuspharma.com/news-events/press-releases/detail/377/corbus-presents-latest-preclinical-data-for-crb-601-at-the-society-for-immunotherapy-of-cancer-sitc-37th-annual-meeting

Corbus Presents Latest Preclinical Data for CRB-601 at the ... The latest preclinical data demonstrate significant tumor growth inhibition by CRB-601 as a single agent and in combination with anti-PD-1 ...

5. researchgate.net researchgate.net/publication/397288218_582_First-in-human_phase_12_study_of_the_integrin_av8-blocking_antibody_CRB-601_in_patients_with_solid_tumors

582 First-in-human phase 1/2 study of the integrin av8- ... In combination with anti-PD-1, CRB-601 not only enhanced anti-PD-1 therapy efficacy in early- and late-stage immune inflamed MC38, but also ...

6. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT06603844

UCSF Solid Tumor Trial → First-in-human Study of CRB-601 ... The purpose of this study is to determine the safety, blood concentrations and treatment effect of CRB-601 in combination with immunotherapy ...

7. corbuspharma.com corbuspharma.com/sites/default/files/2025-05/Corporate%20Presentation%20May%2019%2C%202025.pdf

Corporate Presentation CRB-601 Enhances Anti-PD-1 Therapy in Checkpoint Inhibition Sensitive ... Blockade of αvβ8 in Combination with Anti-PD-1 Increased TIL ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10894349/

The safety and efficacy of anti-PD-1 inhibitor-based ... Anti-programmed cell death 1 (PD-1)-based combinational therapy prolonged patient survival with manageable adverse effects in non-small cell lung cancer (NSCLC) ...