What side effects are associated with this type of intervention?

Common treatments for solid tumors, including those similar to the trispecific Humabody® T-cell enhancer (CB307), often result in side effects such as generalized edema, pruritis, nausea, fatigue, anemia, and decreased appetite. Immunotherapies like pembrolizumab and nivolumab can cause immune-related adverse events, including fatigue, rash, diarrhea, and endocrine disorders. Targeted therapies may lead to hypertension, hypokalemia, and infusion-related reactions.

What prior FDA approvals exist?

The FDA has approved several immunotherapy and targeted therapy drugs for the treatment of solid tumors. Pembrolizumab (Keytruda) and atezolizumab (Tecentriq) are notable examples of immune checkpoint inhibitors that have shown efficacy in various solid tumors, including non-small cell lung cancer and renal cell carcinoma. These drugs work by blocking PD-1/PD-L1 pathways, thereby enhancing the immune system's ability to attack cancer cells. Additionally, drugs like bevacizumab (Avastin), which targets VEGF, have been approved for use in combination with other therapies for certain solid tumors. While specific trispecific Humabody® T-cell enhancers like CB307 are still under investigation, these approved therapies highlight the ongoing advancements in immunotherapy and targeted treatments for solid tumors.

What other types of research exist?

Promising novel alternatives to CB307 for solid tumor patients include: <ol> <li>Pembrolizumab (KEYTRUDA®) - Investigated in combination with other agents like cetuximab for head and neck cancer, showing a 45% response rate in a phase II trial.</li> <li></li> </ol> Utomilumab (PF-05082566) - A 4-1BB/CD137 agonist evaluated in a phase I study for advanced malignancies, showing preliminary clinical activity. 3. Radioimmunotherapy with 124I- or 131I-omburtamab - Targeting B7H3 in CNS malignancies, currently under investigation. 4. Pembrolizumab plus bevacizumab - Evaluated in metastatic renal cell carcinoma, showing efficacy in phase Ib/II trials.

← Back to Search

CAR T-cell Therapy

CB307 for Solid Tumors (POTENTIA Trial)

Q: What is the mechanism of action of this treatment?

Common treatments for solid tumors include immunotherapy and targeted therapy. Immunotherapy, such as immune checkpoint inhibitors, enhances the body's immune response to recognize and attack cancer cells. Targeted therapies inhibit specific molecules involved in tumor growth. The trial CB307 involves a trispecific Humabody® T-cell enhancer targeting PSMA+ tumor cells, which enhances T-cell activation and directs them to attack cancer cells. This is significant for solid tumor patients as it offers a precise and potentially more effective treatment by leveraging the immune system to target cancer cells.

Phase 1

Recruiting

Research Sponsored by Crescendo Biologics Ltd.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

ECOG PS <=2

Aged at least 18 years

Must not have

Subjects with autoimmune disease or regular immunosuppressants

Has brain metastasis including leptomeningeal metastasis or primary brain tumour

Timeline

Screening 3 weeks

Treatment Varies

Follow Up progression-free survival according to recist v1.1 or pcwg3 up to 20 months duration; and change from baseline in anti-drug (cb307) antibodies (ada up to 20 months duration

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new drug called CB307, alone or with another drug, in patients with advanced tumors that are not responding to standard treatments. The drugs work by boosting the body's immune system to better fight the cancer. The other drug has been widely studied and used in various cancers, showing benefits in slowing disease progression and improving survival.

Who is the study for?

This trial is for adults with advanced or metastatic PSMA+ solid tumors who can't be helped by standard treatments. They must understand the consent form, have a performance status indicating they are relatively active, and their organs must function well. People with autoimmune diseases, brain metastases, active infections, CNS disease history, or those intolerant to certain immunotherapies cannot join.

What is being tested?

The study tests CB307 alone and in combination with pembrolizumab (KEYTRUDA®) on patients with specific advanced cancers that express PSMA. It's an early-phase trial to find out the maximum dose people can take without serious side effects and to see how effective these treatments might be.

What are the potential side effects?

Potential side effects of CB307 and pembrolizumab may include immune system reactions affecting various organs, infusion-related responses like fever or chills, fatigue, possible digestive issues such as nausea or diarrhea, skin reactions like rash or itching.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I can take care of myself and perform daily activities.

Select...

I am 18 years old or older.

Select...

My cancer is advanced, spreads to other parts, and tests positive for PSMA.

Select...

My cancer can be measured by scans or blood tests.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have an autoimmune disease or take immunosuppressants regularly.

Select...

My cancer has spread to my brain.

Select...

I currently have an active infection.

Select...

I have or had a brain or spinal cord disease.

Select...

I stopped taking certain cancer immunotherapies due to severe side effects.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ progression-free survival according to recist v1.1 or pcwg3 up to 20 months duration; and change from baseline in anti-drug (cb307) antibodies (ada up to 20 months duration

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~progression-free survival according to recist v1.1 or pcwg3 up to 20 months duration; and change from baseline in anti-drug (cb307) antibodies (ada up to 20 months duration

This trial's timeline: 3 weeks for screening, Varies for treatment, and progression-free survival according to recist v1.1 or pcwg3 up to 20 months duration; and change from baseline in anti-drug (cb307) antibodies (ada up to 20 months duration for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

Number of participants with treatment-related adverse events with CB307 in combination with pembrolizumab as assessed by CTCAE v5.0

Secondary study objectives

Pharmacokinetic of CB307 T1/2

Pharmacokinetic of CB307 Tmax

Relationship of CB307 to anti tumour response

+5 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Multi center open label Dose Escalation followed by Combination Cohort Expansion : Part 2BExperimental Treatment1 Intervention

Patients will receive CB307 IV infused every 7 days in combination with KEYTRUDA® (pembrolizumab) IV infused every 21 days . Duration of treatment cycle is 21 days. Once the Dose Escalation phase (Part 1) is completed Cohort Expansion phase (Part 2) will begin. Part 2B arm will enrol patients with PSMA+ metastatic castration-resistant prostate cancer. Treatment will continue until loss of clinical benefit, intolerable toxicity, withdrawal of consent or the study is stopped. Estimated study duration is 20 months.

Group II: Multi center open label Dose Escalation followed by Cohort Expansion: Part 2AExperimental Treatment1 Intervention

Patients will receive CB307 IV infused every 7 days. Duration of treatment cycle is 21 days. Once the Dose Escalation phase (Part 1) is completed Cohort Expansion phase (Part 2) will begin. Part 2A arm will enrol patients with PSMA+ solid tumours. Treatment will continue until loss of clinical benefit, intolerable toxicity, withdrawal of consent or the study is stopped. Estimated study duration is 20 months.

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for solid tumors include immunotherapy and targeted therapy. Immunotherapy, such as immune checkpoint inhibitors, enhances the body's immune response to recognize and attack cancer cells. Targeted therapies inhibit specific molecules involved in tumor growth. The trial CB307 involves a trispecific Humabody® T-cell enhancer targeting PSMA+ tumor cells, which enhances T-cell activation and directs them to attack cancer cells. This is significant for solid tumor patients as it offers a precise and potentially more effective treatment by leveraging the immune system to target cancer cells.

A pharmacodynamic model of clinical synergy in multiple myeloma.Recent advances in systemic therapy of soft tissue sarcomas.