KZR-261 for Cancer

Recruiting at 11 trial locations

Overseen By Anthony Olszanski, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Kezar Life Sciences, Inc.

Must not be taking: Cytotoxic, Biologic, Targeted therapies

Disqualifiers: CNS metastases, Pulmonary disease, others

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

Compensation: Varies

Number of Visits: 3

Duration: 24 weeks

61 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called KZR-261 for certain advanced cancers, including melanoma, colorectal cancer, prostate cancer, and mesothelioma. The goal is to determine if KZR-261 is safe and effective in shrinking tumors. The trial consists of two parts: the first part identifies the right dose, and the second part evaluates its effectiveness on specific cancers. It seeks patients whose cancer has spread or is too advanced for surgical removal and who have not succeeded with other treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking certain cancer treatments, such as cytotoxic, biologic, or targeted therapies, at least 14 days before starting the study drug. If you are on an investigational drug, you need to stop it 28 days before starting the trial.

Is there any evidence suggesting that KZR-261 is likely to be safe for humans?

Research has shown that KZR-261 was well tolerated in early lab studies before human testing. These studies found that KZR-261 had effects against tumors in different models, both alone and with another cancer treatment called anti-PD-1. This trial is in its early stages, focusing primarily on assessing the treatment's safety for people. Although human testing data is limited, earlier lab results suggest KZR-261 could be safe for future use. However, further studies are necessary to fully understand its safety in people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

KZR-261 is unique because it targets cancer in a way that's different from most existing treatments like chemotherapy and immunotherapy. It involves a new approach by potentially disrupting critical cellular pathways that cancer cells depend on to survive and grow. Researchers are excited about KZR-261 because it could offer a new option for patients with tough-to-treat cancers, such as melanoma, colorectal cancer, prostate cancer, and mesothelioma, by possibly overcoming resistance to current therapies. This innovative mechanism of action could lead to more effective treatments with potentially fewer side effects, bringing hope to patients and their families.

What evidence suggests that KZR-261 might be an effective treatment for cancer?

Research has shown that KZR-261 is a new and promising cancer treatment. Studies indicate that KZR-261 works by blocking Sec61 proteins, which aid cancer cell growth. Early lab tests found that KZR-261 reduced tumor size at doses much lower than the highest safe dose. This trial will evaluate KZR-261 combined with standard therapy for various solid tumors, including melanoma and colorectal cancer. Initial results are encouraging, but further research is needed to confirm its effectiveness in people. ^{1 3 6 7 8}

Who Is on the Research Team?

Kezar Study Director

Principal Investigator

Kezar Life Sciences, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that haven't responded to standard treatments, or where no standard treatment exists. Participants must be willing to use contraception and have a performance status indicating they are fully active or restricted in physically strenuous activity but ambulatory. They can't join if they've had recent cancer therapy, surgery, radiation, are pregnant/breastfeeding, have heart rhythm risks, uncontrolled lung disease, or CNS malignancies.

Inclusion Criteria

My cancer (melanoma, colorectal, prostate, or mesothelioma) has been confirmed by lab tests.

My cancer has spread or can't be removed by surgery and isn't primarily in the brain.

My disease did not respond to or came back after standard treatment, or I refused such treatment.

Exclusion Criteria

Any female who is breastfeeding or who plans to become pregnant during the study, or who are actively trying to conceive at the time of signing of the informed consent form (ICF)

Subjects who have participated in Part 1 dose escalation are not eligible to enroll in Part 2 dose expansion

I have a serious lung condition that is not under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive KZR-261 in a dose escalation and expansion format to evaluate safety, tolerability, and preliminary anti-tumor activity

24 weeks

3 doses in a 28-day cycle

Safety Follow-up

Participants are monitored for safety after the treatment period

4-6 weeks

Long-Term Follow-up

Participants are monitored for long-term safety and efficacy outcomes

12 months

What Are the Treatments Tested in This Trial?

Interventions

• KZR-261

Trial Overview The study tests KZR-261's safety and effectiveness against various solid tumors including melanoma and colorectal cancer. It has two parts: Dose Escalation to find the safe dosage level and Dose Expansion to further evaluate this dose in specific cancers. The goal is also to determine the best Phase 2 dose.

How Is the Trial Designed?

Group I: KZR-261 with standard therapy: open-label Experimental Treatment 1 Intervention

Part 1 (Dose Escalation) The initial dose cohort of the Dose Escalation will receive 1.8 mg/m2 of KZR-261. Subjects will receive 3 doses in a 28-day cycle. \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ Part 2 (Dose Expansion) Following safety review of all Dose Escalation cohorts and determination of the maximum tolerated dose (MTD) or maximum administered dose (MAD), KZR-261 will be evaluated for safety and preliminary efficacy in 4 tumor-specific cohorts and 1 all-tumor cohort to determine the recommended phase 2 dose (RP2D). The 4 tumor-specific cohorts will include: * melanoma (including uveal melanoma) * colorectal cancer * prostate cancer * mesothelioma

Who Is Running the Clinical Trial?

Kezar Life Sciences, Inc.

Lead Sponsor

Trials

7

Recruited

280+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05047536

KZR-261 in Subjects With Advanced Solid Malignancies A first-in-human, open-label, multicenter, Phase 1 study of KZR-261 designed to assess the safety and tolerability, preliminary anti-tumor activity, ...

2. ucla.clinicaltrials.researcherprofiles.org ucla.clinicaltrials.researcherprofiles.org/trial/NCT05047536

KZR-261 in Subjects With Advanced Solid Malignancies A first-in-human, open-label, multicenter, Phase 1 study of KZR-261 designed to assess the safety and tolerability, preliminary anti-tumor ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0022356525398472

Preclinical characterization of novel multi-client inhibitors ... KZR-834 and KZR-261 are novel Sec61 inhibitors with the ability to block multiple Sec61 client proteins, leading to well-tolerated efficacy in in vivo cancer ...

4. georgiacancerinfo.net georgiacancerinfo.net/clinical-trials/detail/5285

KZR-261 in Subjects With Advanced Solid Malignancies Summary. A first-in-human, open-label, multicenter, Phase 1 study of KZR-261 designed to assess the safety and tolerability, preliminary anti-tumor activity ...

5. researchgate.net researchgate.net/publication/341636949_Preclinical_evaluation_of_KZR-261_a_novel_small_molecule_inhibitor_of_Sec61

(PDF) Preclinical evaluation of KZR-261, a novel small ... Anti-tumor activity was >50% at doses 1/3rd of the maximum tolerated dose, suggesting a broad therapeutic index. 8834 was also effective in the ...

6. ir.kezarlifesciences.com ir.kezarlifesciences.com/static-files/bb2c4967-9567-4b04-a07d-b684afa202c8

Form 8-K for Kezar Life Sciences INC filed 08/13/2024 Kezar's oncology product candidate, KZR-261, targe ng the Sec61 translocon and protein secre on pathway, is being evaluated in an open-label ...

7. sec.gov sec.gov/Archives/edgar/data/0001645666/000156459021043959/kzr-ex991_6.htm

kzr-ex991_6.htm The company plans to initiate a Phase 1 clinical trial of KZR-261, which will assess safety, tolerability and preliminary tumor activity of KZR-261 in solid ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.3582

Preclinical evaluation of KZR-261, a novel small molecule ... Clinical trials are being planned with KZR-261 to understand safety and early efficacy of this novel compound and therapeutic target. This ...