CX-904 for Advanced Solid Cancers

No longer recruiting at 4 trial locations

Overseen By Karen Deane

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: CytomX Therapeutics

Disqualifiers: Active malignancy, Autoimmune diseases, Myocarditis, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CX-904, an experimental therapy for individuals with advanced solid tumors—cancers that have spread or cannot be surgically removed. The trial aims to assess the safety and effectiveness of CX-904 and to understand how the body processes it. This trial may suit someone with a solid tumor unresponsive to standard treatments. Participants must have a measurable tumor and be in good overall health despite their cancer. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that CX-904 is likely to be safe for humans?

Research has shown that CX-904, a treatment for some advanced cancers, has been safe in early studies. In trials where patients with advanced or spreading solid tumors received it alone, no cases of cytokine release syndrome (a severe immune reaction) occurred. This suggests the treatment is well-tolerated in humans, at least in the early testing stages. While this is encouraging, the treatment remains in the early testing phase, so ongoing studies are crucial to confirm its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

CX-904 is unique because it targets solid tumors in a new way, potentially offering an option where current treatments like chemotherapy, radiation, and surgery may fall short. Traditional treatments often attack both cancerous and healthy cells, leading to significant side effects. But CX-904 is designed to specifically target cancer cells, which could mean fewer side effects and better outcomes for patients. Researchers are excited about this treatment because it promises a more precise approach, potentially leading to more effective and safer cancer care.

What evidence suggests that CX-904 might be an effective treatment for advanced solid cancers?

Research has shown that CX-904, the investigational treatment in this trial, may effectively treat advanced solid tumors. Early results suggest safety, with no reports of cytokine release syndrome, an immune reaction. CX-904 engages T-cells by targeting both EGFR, a protein often abundant in cancer cells, and CD3, a molecule on T-cells that aids in fighting disease. This mechanism may help the body attack cancer. Initial data indicate that CX-904 alone has shown signs of fighting tumors. These early findings offer hope for its effectiveness in treating certain cancers. ^{1 2 3 6 7}

Who Is on the Research Team?

Monika Vainorius, M.D.

Principal Investigator

CytomX Therapeutics, Inc

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that can't be surgically removed and have spread. They should have tried standard treatments already, not have serious heart issues or autoimmune diseases, and agree to use effective birth control. Those with small, symptom-free brain metastases may join after special consideration.

Inclusion Criteria

Adequate baseline laboratory values

I have small brain tumors (≤1 cm) that need treatment.

Patients of childbearing potential or those with partners of childbearing potential must agree to use a highly effective method of birth control from signing the ICF, and for a period of 30 days after the last dose of CX-904.

Exclusion Criteria

I had cancer within the last 2 years, but it's considered cured and low risk of coming back.

Additional exclusion criteria may apply

Screening electrocardiogram demonstrating a mean QTcF value > 480 msec; a screening echocardiogram with left ventricular ejection fraction (LVEF) < 50%

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of CX-904 to determine safety and tolerability

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 months

What Are the Treatments Tested in This Trial?

Interventions

• CX-904

Trial Overview The study tests CX-904's safety and effectiveness in treating advanced solid tumors. It will assess how the body processes the drug (PK), its impact on the tumor (PD), tolerability at different doses, and any potential benefits in shrinking or controlling tumor growth.

How Is the Trial Designed?

Group I: CX-904 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

CytomX Therapeutics

Lead Sponsor

Trials

9

Recruited

1,000+

Published Research Related to This Trial

CX-072, an anti-PD-L1 Probody therapeutic, is designed to be activated specifically in the tumor microenvironment, which may enhance its efficacy while minimizing effects on healthy tissues.

Preliminary data from a study involving 130 subjects indicated that CX-072 maintains a stable pharmacokinetic profile, with simulations suggesting that a fixed dose of 800 mg would effectively achieve the desired therapeutic levels in most patients, without significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Model-Informed Drug Development of the Masked Anti-PD-L1 Antibody CX-072. Stroh, M., Green, M., Millard, BL., et al.[2021]

TNB-928B is a novel T-cell engager designed to selectively target tumor cells overexpressing folate receptor alpha (FRα), minimizing damage to healthy tissues with low FRα expression, which enhances its safety profile.

In preclinical mouse models of ovarian cancer, TNB-928B demonstrated effective tumor clearance and T-cell activation while inducing minimal cytokine release, suggesting a favorable therapeutic window for treating solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A T-cell engaging bispecific antibody with a tumor-selective bivalent folate receptor alpha binding arm for the treatment of ovarian cancer. Avanzino, BC., Prabhakar, K., Dalvi, P., et al.[2022]

CX-2029, a Probody-drug conjugate targeting CD71, was evaluated in a phase I study with 45 patients, showing that it can be administered safely at doses up to 4 mg/kg, with a recommended phase II dose of 3 mg/kg due to dose-limiting toxicities observed at higher levels.

The study demonstrated preliminary efficacy with confirmed partial responses in three patients with squamous cell tumors, highlighting the potential of CX-2029 to target a previously undruggable receptor while minimizing off-tumor toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I, First-in-Human Study of the Probody Therapeutic CX-2029 in Adults with Advanced Solid Tumor Malignancies. Johnson, M., El-Khoueiry, A., Hafez, N., et al.[2023]

The novel nanobody-based trispecific T cell engager (Nb-TriTE) effectively targets tumor cells and enhances T cell activation, leading to significant tumor killing and improved survival in mouse models of solid tumors.

Unlike traditional therapies, Nb-TriTE demonstrated the ability to overcome tumor-mediated immunosuppression without causing toxicity, suggesting it could be a safer and more effective treatment option for patients with solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanobody-based trispecific T cell engager (Nb-TriTE) enhances therapeutic efficacy by overcoming tumor-mediated immunosuppression. Ding, Z., Sun, S., Wang, X., et al.[2023]

Antibody-based immunotherapies, particularly immune checkpoint inhibitors (ICIs), have significantly improved cancer treatment outcomes but are associated with severe immune-related adverse events (irAEs) that can limit treatment duration and cause high morbidity.

Probody therapeutics, a new class of antibody prodrugs designed to activate specifically within the tumor microenvironment, show promise in maintaining anticancer efficacy while potentially reducing the incidence of irAEs compared to traditional antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probody Therapeutics: An Emerging Class of Therapies Designed to Enhance On-Target Effects with Reduced Off-Tumor Toxicity for Use in Immuno-Oncology. Autio, KA., Boni, V., Humphrey, RW., et al.[2023]

The probody therapeutic CX-2029, designed to target the CD71 antigen, showed potent tumor growth inhibition in over 80% of preclinical patient-derived xenograft models, indicating strong efficacy as a cancer treatment.

CX-2029 demonstrated a significantly improved safety profile, with over 80% of the drug remaining inactive in circulation, leading to a 10-fold increase in tolerability compared to traditional anti-CD71 antibody-drug conjugates, which were lethal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonclinical Efficacy and Safety of CX-2029, an Anti-CD71 Probody-Drug Conjugate. Singh, S., Serwer, L., DuPage, A., et al.[2023]

The study of 89Zr-CX-072, a PD-L1-targeting Probody therapeutic, demonstrated significant tumor uptake in patients, even in tumors with low PD-L1 expression (≤1%), indicating its potential effectiveness in a broader range of tumors.

PET imaging showed that 89Zr-CX-072 had a favorable safety profile, with no unexpected uptake in healthy tissues and modest uptake in normal lymphoid organs, suggesting it could be a safe option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Study of the Biodistribution and Pharmacokinetics of 89Zr-CX-072, a Novel Immunopet Tracer Based on an Anti-PD-L1 Probody. Kist de Ruijter, L., Hooiveld-Noeken, JS., Giesen, D., et al.[2022]

Probody therapeutics (Pb-Tx) targeting PD-1 and PD-L1 showed similar antitumor effects as traditional antibodies while significantly reducing systemic activity and toxicity, particularly in preventing autoimmune diabetes in mice.

The localized action of Pb-Tx allows for effective tumor treatment with minimized side effects, supporting the ongoing clinical trials of the anti-PD-L1 Pb-Tx CX-072.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conditional PD-1/PD-L1 Probody Therapeutics Induce Comparable Antitumor Immunity but Reduced Systemic Toxicity Compared with Traditional Anti-PD-1/PD-L1 Agents. Assi, HH., Wong, C., Tipton, KA., et al.[2023]

The study established the maximum tolerated dose (MTD) of the Probody immune checkpoint inhibitor CX-072 (pacmilimab) combined with ipilimumab as 10 mg/kg and 3 mg/kg respectively, administered every 3 weeks, showing a favorable safety profile with manageable adverse effects.

Among the 27 patients treated, the overall response rate was 19%, with notable long-lasting responses in some patients, indicating potential efficacy in advanced solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CX-072 (pacmilimab), a Probody PD-L1 inhibitor, in combination with ipilimumab in patients with advanced solid tumors (PROCLAIM-CX-072): a first-in-human, dose-finding study. Sanborn, RE., Hamid, O., de Vries, EG., et al.[2022]

CX-2009, a Probody drug conjugate targeting CD166, shows effective tumor targeting in a lung cancer mouse model, with comparable biodistribution to other constructs, indicating its potential for treating CD166-expressing tumors.

The study suggests that the enzymatic activation of CX-2009 within the tumor microenvironment does not hinder its ability to target tumors, but further clinical studies are needed to confirm its reduced binding to healthy tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The tumor targeting performance of anti-CD166 Probody drug conjugate CX-2009 and its parental derivatives as monitored by 89Zr-immuno-PET in xenograft bearing mice. Chomet, M., Schreurs, M., Nguyen, M., et al.[2021]

Citations

1. ir.cytomx.com ir.cytomx.com/news-releases/news-release-details/cytomx-therapeutics-announces-positive-initial-phase-1a-dose

CytomX Therapeutics Announces Positive Initial Phase 1a ... CX-904 demonstrated a favorable safety profile with no cytokine release syndrome (CRS) of any grade observed in step-dosing cohorts and no ...

2. onclive.com onclive.com/view/cx-904-generates-a-favorable-safety-profile-in-phase-1-trial-of-egfr-expressing-solid-tumors

CX-904 Generates a Favorable Safety Profile in Phase 1 ... The T-cell engager CX-904 had a favorable safety profile when administered as monotherapy in patients with advanced or metastatic solid tumors.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05387265

NCT05387265 | A Trial to Find Safe and Active Doses for ... This is a first-in-human study evaluating the safety, tolerability, and activity of CX-904, a conditionally activated T-cell bispecific to EGFR and CD3. The ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11794264/

Prodrug-based bispecific antibodies for cancer therapy CX-904 is undergoing evaluation in a phase 1 study (NCT05387265) for patients with advanced metastatic solid tumors commonly expressing EGFR.

5. firstwordpharma.com firstwordpharma.com/story/5883890

CytomX Therapeutics Reports Second Quarter 2024 ... “We are encouraged by the initial CX-904 Phase 1a data we shared in the second quarter that demonstrated single agent anti-cancer activity and a ...

6. aacrjournals.org aacrjournals.org/cancerres/article/82/22/4288/710123/A-Probody-T-Cell-Engaging-Bispecific-Antibody

A Probody T Cell–Engaging Bispecific Antibody Targeting ... A probody T cell–engaging bispecific antibody targeting EGFR and CD3 inhibits colon cancer growth with limited toxicity.

7. clin.larvol.com clin.larvol.com/trial-detail/NCT05387265

A Trial to Find Safe and Active Doses for an Investigational ... CX-904 is a conditionally activated T-cell-engaging bispecific (TCB) designed to target the epidermal growth factor receptor (EGFR) on cancer cells.