CRX100 for Solid Cancers

Recruiting at 2 trial locations

Overseen By Jennifer Lindal

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: BioEclipse Therapeutics

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Brain metastasis, Active infections, Autoimmune disease, HIV, others

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

Compensation: Varies

Number of Visits: 109

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests CRX100, a new treatment for several advanced solid cancers, either alone or combined with Pembrolizumab, another cancer drug. The main goals are to assess the treatment's safety and effectiveness. It targets cancers such as non-small cell lung cancer, ovarian cancer, and others. Suitable participants have been dealing with these cancers for some time and have not found success with other treatments. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you cannot participate if you have received chemotherapy, immunotherapies, or certain other treatments within three weeks of enrollment, or cell-based therapies within 12 weeks. It's best to discuss your specific medications with the trial team.

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

Research is investigating the safety of CRX100 for individuals with advanced solid tumors. Specific safety data is not yet available, but the studies aim to assess how well participants tolerate the treatment. As a Phase 1 trial, the primary goal is to evaluate safety, and potential risks are still under exploration.

For the combination of CRX100 with Pembrolizumab, it is important to note that Pembrolizumab is already approved for some cancers and is generally well-tolerated. However, using it with CRX100 is novel, and this trial will help determine their combined safety.

Researchers are monitoring for any side effects and their severity. These early trials are crucial to ensure the safety of any treatment before broader use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

CRX100 is unique because it targets solid cancers with a novel approach that combines monotherapy and combination therapy with Pembrolizumab. Unlike traditional treatments that often rely solely on chemotherapy or radiation, CRX100 offers a new mechanism of action by potentially enhancing the immune response against tumors when used with Pembrolizumab. Researchers are excited because this could lead to more effective treatments with fewer side effects, especially for patients with advanced or treatment-resistant cancers. Additionally, the flexible dosing schedule and the possibility of additional doses based on patient response offer a tailored treatment approach that might improve patient outcomes.

What evidence suggests that CRX100 might be an effective treatment for solid cancers?

Research shows that CRX100 could help treat advanced solid tumors. In earlier studies, CRX100 prompted the creation of a specific type of immune cell in patients with ovarian cancer, indicating promise. This suggests CRX100 might enhance the immune system's ability to identify and attack cancer cells. In this trial, some participants will receive CRX100 alone, while others will receive it with Pembrolizumab, a current cancer treatment. Combining CRX100 with Pembrolizumab aims to strengthen this effect, potentially improving the body's ability to fight cancer. Although still in early stages, these findings offer hope for those dealing with various solid cancers. ^{3 5 6 7 8}

Who Is on the Research Team?

Oliver Dorigo

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

Adults over 18 with advanced solid tumors like certain breast, colorectal, liver, bone, ovarian or stomach cancers can join. They should be recovered from past treatments and free of active infections. Participants must have measurable cancer on scans and agree to use contraception. Those with recent immunosuppressants, other cancers or treatments, serious illnesses including HIV/hepatitis B/C or brain metastasis cannot join.

Inclusion Criteria

I will use effective birth control during and for 6 months after the study.

I have recovered from recent surgery, radiation, or chemotherapy.

My cancer can be measured by scans and has at least one visible tumor.

Exclusion Criteria

I or someone I live with has a significant immune system problem.

I haven't had experimental drugs or immunotherapy in the last 3 weeks.

I have or had an autoimmune disease, with some exceptions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Monotherapy Dose-Escalation

Participants receive CRX100 as monotherapy with dose escalation to determine safety and tolerability

Up to 36 weeks

Infusions every 9 weeks, up to 4 infusions

Combination Therapy

Participants receive CRX100 in combination with Pembrolizumab to evaluate safety and anti-tumor activity

Up to 36 weeks

CRX100 infusions every 9 weeks, Pembrolizumab every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• CRX100

Trial Overview CRX100 is being tested in this phase 1 trial for safety and how the body processes it. It involves taking patients' immune cells out (leukapheresis), treating them to become 'cytokine induced killer cells', then putting them back into the patient to fight cancer.

How Is the Trial Designed?

Group I: Monotherapy Dose-Escalation Cohorts Experimental Treatment 3 Interventions

Prior to the current amendment, no DLTs were observed at Dose Levels 1-5. Starting with the current protocol amendment, dosing decisions in monotherapy cohorts will utilize a 3+3 design for Dose Level 6. CRX100 infusion will occur every nine weeks (+/- 7 days). Subjects will receive up to a maximum of four infusions of CRX100 unless it is determined by the treating physician and the sponsor that it is in the best interest of the subjects to receive additional doses of CRX100 beyond four doses. A minimum of three DLT-evaluable subjects will be doses at Dose Level 6 and expanded to six subjects if determined necessary based on DLT incidence using the 3+3 design, and discussion with SRC and Sponsor.

Group II: Combination Therapy Cohorts Experimental Treatment 3 Interventions

Subjects with relasped or refractory solid tumors, as defined in the inclusion criteria, will be enrolled to evaluate the safety and anti-tumor activity of CRX100 in combination with Pembrolizumab in patients with advanced solid malignancies. The dose of CRX100 used will be determined from the monotherapy cohorts. CRX100 infusion will occur every nine weeks (+/- 7 days). Subjects will receive up to a maximum of four doses of CRX100 unless it is determined by the treating physician and the sponsor that it is in the best interest of the subjects to receive additional doses of CRX100 beyond four doses. Pembrolizumab will be administered at 200mg IV every three weeks (Q3W) per the approved label.

Who Is Running the Clinical Trial?

BioEclipse Therapeutics

Lead Sponsor

Trials

1

Recruited

60+

Published Research Related to This Trial

The novel CRM1 inhibitor KPT-185 effectively reduced the viability of non-small cell lung cancer (NSCLC) cell lines, including those resistant to EGFR-TKIs, by inducing cell cycle arrest and apoptosis in a dose-dependent manner.

In an in vivo mouse model, the clinical analog KPT-276 significantly inhibited tumor growth without causing significant side effects, indicating its potential as a safe therapeutic option for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor effects of a novel chromosome region maintenance 1 (CRM1) inhibitor on non-small cell lung cancer cells in vitro and in mouse tumor xenografts. Wang, S., Han, X., Wang, J., et al.[2023]

Elevated levels of HOXC10 in colorectal cancer (CRC) patients are associated with increased metastasis, poorer tumor differentiation, and worse overall prognosis, making it a significant independent predictor of patient outcomes.

Targeting the HOXC10-CXCL5-MDSC pathway with CXCR2 inhibitors or anti-PD-L1 treatments shows promise in reducing CRC metastasis, suggesting new therapeutic strategies for patients with high HOXC10 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HOXC10 Promotes Metastasis in Colorectal Cancer by Recruiting Myeloid-derived Suppressor Cells. Yu, J., Chen, X., Zhao, S., et al.[2022]

CRX (OTX3) is a transcription factor that is crucial for the development of retinal and pineal cells, and it is selectively expressed in retinoblastomas and pineal tumors, making it a potential marker for diagnosing these cancers.

In a study of 89 central nervous system tumors, CRX was found to be a strong marker in normal pineal tissue and pineal tumors, but its absence does not completely rule out the diagnosis of pineal parenchymal tumors, especially in small biopsy samples.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CRX/OTX3: a useful marker in the differential diagnosis of tumors of the pineal region and indicator of photoreceptor differentiation in medulloblastomas and atypical teratoid rhabdoid tumors. Gielen, GH., Gessi, M., Denkhaus, D., et al.[2016]

Crm1, a nuclear export receptor, is significantly overexpressed in oesophageal squamous cell carcinoma compared to normal tissues, indicating its potential role in cancer progression.

Inhibiting Crm1 expression in oesophageal cancer cells led to reduced cell proliferation and increased apoptosis, suggesting that targeting Crm1 could be a promising therapeutic strategy with minimal effects on normal oesophageal cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elevated expression of the nuclear export protein, Crm1 (exportin 1), associates with human oesophageal squamous cell carcinoma. van der Watt, PJ., Zemanay, W., Govender, D., et al.[2023]

CRX is a transcription factor that is specifically expressed in retinal and pineal cells, and its strong expression in over 95% of retinoblastomas and pineal parenchymal tumors suggests it could serve as a sensitive and specific clinical marker for these cancers.

The study indicates that CRX may also be a potential therapeutic target for retinoblastoma and pineoblastoma, as it is not commonly found in other tumors, making it a promising candidate for lineage-dependent cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CRX is a diagnostic marker of retinal and pineal lineage tumors. Santagata, S., Maire, CL., Idbaih, A., et al.[2021]

In a phase 1 study involving 44 pediatric patients with refractory solid tumors and ALCL, the recommended phase 2 dose (RP2D) of crizotinib in combination with topotecan and cyclophosphamide was determined to be 215 mg/m2/dose taken twice daily, showing it can be safely tolerated at this dosage.

The study found that while the oral solution of crizotinib was not well tolerated due to palatability issues, the crizotinib formulated capsules were more acceptable, although they led to increased toxicity that requires further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability and pharmacokinetics of crizotinib in combination with cytotoxic chemotherapy for pediatric patients with refractory solid tumors or anaplastic large cell lymphoma (ALCL): a Children's Oncology Group phase 1 consortium study (ADVL1212). Greengard, E., Mosse, YP., Liu, X., et al.[2021]

VX15/2503 was well tolerated in a study of 42 patients with advanced solid tumors, with most side effects being mild (grade 1 or 2), such as nausea and fatigue, indicating a favorable safety profile.

The treatment showed promising antitumor activity, with one patient achieving a partial response and 45.2% of patients maintaining stable disease for at least 8 weeks, suggesting that VX15/2503 may enhance immune response against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Pharmacokinetics, and Pharmacodynamics of a Humanized Anti-Semaphorin 4D Antibody, in a First-In-Human Study of Patients with Advanced Solid Tumors. Patnaik, A., Weiss, GJ., Leonard, JE., et al.[2022]

The North Central Cancer Treatment Group developed a real-time toxicity reporting system to enhance the monitoring of severe side effects in NCI-sponsored clinical trials, aiming to improve patient safety.

This system has been effective in monitoring phase II and III trials, such as the N9741 study on advanced colorectal cancer, allowing for timely modifications to ongoing clinical trials based on reported adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early detection of toxicity and adjustment of ongoing clinical trials: the history and performance of the North Central Cancer Treatment Group's real-time toxicity monitoring program. Goldberg, RM., Sargent, DJ., Morton, RF., et al.[2016]

In the DESTINY-CRC01 trial involving 86 patients with HER2-expressing metastatic colorectal cancer, trastuzumab deruxtecan (T-DXd) showed a significant objective response rate of 45.3% in patients with HER2-positive tumors (cohort A), while no responses were observed in cohorts with lower HER2 expression.

The treatment demonstrated a median progression-free survival of 6.9 months and an overall survival of 15.5 months, with manageable safety concerns, including a 9.3% incidence of drug-related interstitial lung disease/pneumonitis, indicating T-DXd's potential as a targeted therapy for HER2-positive mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer. Yoshino, T., Di Bartolomeo, M., Raghav, K., et al.[2023]

In a multicenter phase II study involving 71 patients with metastatic breast cancer, Caelyx (Doxil) demonstrated an overall response rate of 31%, with 16 patients achieving a partial or complete response, indicating its efficacy in treating advanced breast cancer.

The safety profile of Caelyx was favorable, with significant neutropenia and mucositis occurring in only 10% of treatment cycles, and a lower incidence of severe skin toxicity at a dose of 45 mg/m2 every 4 weeks, suggesting it is well-tolerated and suitable for combination chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of advanced breast cancer with sterically stabilized liposomal doxorubicin: results of a multicenter phase II trial. Ranson, MR., Carmichael, J., O'Byrne, K., et al.[2017]

Citations

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Study of CRX100 Makes Progress in Patients With ... The study has a primary outcome of adverse events (AEs) and dose-limiting toxicities (DLTs), which will be measured based on the frequency of ...

2. stanfordhealthcare.org stanfordhealthcare.org/trials/s/NCT04282044.html

Study of CRX100 as Monotherapy and in Combination ... This clinical study is an open-label, Phase 1, dose-escalation study to determine the safety, tolerability, and efficacy of the drug product produced by ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04282044?cond=%22Osteogenic%20Sarcoma%22&intr=%22Pembrolizumab%22&viewType=Table&rank=8

Study of CRX100 as Monotherapy and in Combination ... There are three types of violations: Failure to submit required clinical trial information; Submission of false or misleading clinical trial information ...

4. cancernetwork.com cancernetwork.com/view/crx100-yields-responses-tolerability-in-platinum-resistant-ovarian-cancer

CRX100 Yields Responses, Tolerability in Platinum ... Ex vivo generation of CD3-positive, CD56-positive Natural Killer-Like (NKT) with CRX100 was successful in all 7 patients with ovarian cancer in a phase 1 trial.

5. trialx.com trialx.com/clinical-trials/listings/221978/study-of-crx100-as-monotherapy-and-in-combination-with-pembrolizumab-in-patients-with-advanced-solid-malignancies/

Study of CRX100 as Monotherapy and in Combination ... This clinical study is an open-label, Phase 1, dose-escalation study to determine the safety, tolerability, and efficacy of the drug product ...

6. withpower.com withpower.com/trial/phase-1-triple-negative-breast-neoplasms-2021-842f5?condition=&overallStatus=Recruiting&hasNoPlacebo=false&query=Uveal+Melanoma

CRX100 for Solid Cancers There is no specific safety data available for CRX100, but similar treatments like crizotinib have been studied for safety in children with solid tumors, and ...

7. bioeclipse.com bioeclipse.com/2020/12/21/bioeclipse-initiates-enrollment-in-phase-1-dose-escalation-clinical-trial-for-crx100/

BioEclipse Initiates Enrollment in Phase 1 Dose-Escalation ... This open-label, Phase 1 dose-escalation study is designed to determine the safety, tolerability, and pharmacokinetic (PK) properties of CRX100 ...

8. cirm.ca.gov cirm.ca.gov/our-progress/awards/phase-1-open-label-dose-escalation-study-crx100-patients-advanced-solid-tumors/

PHASE 1, OPEN LABEL, DOSE-ESCALATION STUDY OF ... PHASE 1, OPEN LABEL, DOSE-ESCALATION STUDY OF CRX100 IN PATIENTS WITH ADVANCED SOLID TUMORS ... Immune cells loaded with a cancer-killing virus that targets ...