AB521 for Renal Cell Carcinoma

(ARC-20 Trial)

Recruiting in Palo Alto (17 mi)

+32 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Arcus Biosciences, Inc.

Must not be taking: HIF-2α inhibitors, Cabozantinib

Disqualifiers: Cardiac, Respiratory, Psychiatric, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called AB521 to see if it is safe for people with advanced cancers, including a type of kidney cancer called clear cell renal cell carcinoma. In some parts of the study, AB521 will be used alone, and in others, it will be combined with another drug called cabozantinib, which stops cancer cells from growing.

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. However, you cannot have had certain treatments like a HIF-2α inhibitor or cabozantinib before joining the trial.

What makes the drug AB521 (casdatifan) unique for treating renal cell carcinoma?

AB521 (casdatifan) is unique because it targets the HIF-2α pathway, which is involved in tumor growth and resistance to other treatments. This mechanism is different from many existing therapies that focus on inhibiting blood vessel growth or modulating the immune system.

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Eligibility Criteria

This trial is for adults with advanced solid tumors or clear cell renal cell carcinoma (ccRCC) who have tried other treatments without success. They must have had prior anti-PD-1 therapy and a TKI, no HIF-2α-targeting therapy, at least one measurable tumor lesion, and be in good physical condition with an ECOG score of ≤ 1.

Inclusion Criteria

I am fully active or have some restrictions but can still care for myself.

I have kidney cancer, treated with specific drugs but not HIF-2α inhibitors.

I have a solid tumor cancer with no other treatment options left.

Exclusion Criteria

I have not received any live vaccines in the last 4 weeks.

I have not had major surgery or serious injury in the last 28 days.

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive casdatifan orally once or twice daily to determine the safety and tolerability of the drug

8-12 weeks

Dose Expansion

Participants receive casdatifan monotherapy or in combination with cabozantinib or zimberelimab to further evaluate safety and efficacy

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Participant Groups

The study tests the safety and tolerability of AB521 as a solo treatment for patients with various advanced solid tumors including ccRCC. It aims to find out how well participants handle this new drug and what effects it has on their cancer.

Group I: Dose Expansion Cohort 8 Experimental Treatment 1 Intervention

Participants will receive casdatifan orally

Group II: Dose Expansion Cohort 7 Experimental Treatment 2 Interventions

Participants will receive casdatifan orally with zimberelimab infusion

Group III: Dose Expansion Cohort 6 Experimental Treatment 1 Intervention

Participants will receive casdatifan orally

Group IV: Dose Expansion Cohort 5 Experimental Treatment 1 Intervention

Participants will receive casdatifan orally

Group V: Dose Expansion Cohort 4 Experimental Treatment 2 Interventions

Participants will receive casdatifan orally with with cabozantinib orally

Group VI: Dose Expansion Cohort 3 Experimental Treatment 1 Intervention

Participants will receive casdatifan orally

Group VII: Dose Expansion Cohort 2 Experimental Treatment 1 Intervention

Participants will receive casdatifan orally

Group VIII: Dose Expansion Cohort 1 Experimental Treatment 1 Intervention

Participants will receive casdatifan orally

Group IX: Dose Escalation Cohort 5 Experimental Treatment 1 Intervention

Participants will receive casdatifan orally once daily

Group X: Dose Escalation Cohort 4 Experimental Treatment 1 Intervention

Participants will receive casdatifan orally once daily

Group XI: Dose Escalation Cohort 3 Experimental Treatment 1 Intervention

Participants will receive casdatifan orally twice daily

Group XII: Dose Escalation Cohort 2 Experimental Treatment 1 Intervention

Participants will receive casdatifan orally once daily

Group XIII: Dose Escalation Cohort 1 Experimental Treatment 1 Intervention

Participants will receive casdatifan orally once daily

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

UCLA Santa Monica, CA

Vanderbilt-Ingram Cancer Center Nashville, TN

Johns Hopkins Hospital Baltimore, MD

Next Oncology Virginia New York, NY

More Trial Locations

Who Is Running the Clinical Trial?

Arcus Biosciences, Inc. Lead Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

LITESPARK-011: belzutifan plus lenvatinib vs cabozantinib in advanced renal cell carcinoma after anti-PD-1/PD-L1 therapy. [2023] The first-in-class, small molecule HIF-2α inhibitor, belzutifan, has demonstrated promising antitumor activity in previously treated patients with clear cell renal cell carcinoma (RCC). HIF-2α also regulates VEGF expression and is involved in resistance to anti-VEGF therapy. This study describes the rationale and design for a randomized, phase III study evaluating efficacy and safety of belzutifan plus the tyrosine kinase inhibitor (TKI) lenvatinib versus the TKI cabozantinib in patients with advanced RCC progressing after anti-PD-1/PD-L1 therapy in the first- or second-line setting or as adjuvant therapy. Considering the unmet need for effective and tolerable treatment of advanced RCC following immune checkpoint inhibitors, belzutifan plus lenvatinib may have a positive benefit/risk profile. Clinical Trial Registration: NCT04586231 (ClinicalTrials.gov).

2. England pubmed.ncbi.nlm.nih.gov

Is the expression of multidrug resistance gene product a prognostic indicator for the clinical outcome of patients with renal cancer? [2019] To determine the significance of the expression of the multidrug resistance gene product (MDR-1) for the aggressiveness of renal cell carcinoma (RCC).

3. Germany pubmed.ncbi.nlm.nih.gov

[Molecular tumor board-renal cell carcinoma]. [2021] The introduction of molecular targeted agents has fundamentally changed the treatment of metastatic renal cell carcinoma. A first wave of development was based on the improved understanding of tumor biology since the discovery of the importance of the von Hippel-Lindau gene as the key driver of the disease and paved the way for antiangiogenic agents. Of relevance is the overexpression of proangiogenic and proliferation-promoting factors (VEGF, vascular endothelial growth factor; PDGF, platelet-derived growth factor) as well as an overactivation of the PI3K-Akt signaling pathway: the target structure is the "mammalian target of rapamycin" (mTOR) molecule, which is involved in the regulation of cell proliferative processes. VEGF-, PDGF-, and mTOR-signals and signaling pathways are central targets of current targeted substances. A second wave is certainly to be seen in the development of therapeutic approaches with the targeted activation and modulation of the immune system, which has brought "immunotherapy" back into the focus of interest. Central development is the application of immune-checkpoint inhibitors, with the help of which (re-)activation of the cellular defense, especially of T cells, takes place, which per se holds the potential of a cytoreductive therapy by killing the tumor cells. Even though the prognosis has improved significantly due to the rapid development of recent years, treatment remains challenging as most patients experience progress, and long-term survival is only achieved in about 20% of cases because some patients are primarily refractory or do not respond. The more intensive interlocking of molecular biology, pathology, clinical research, and interdisciplinary uro-oncology, as is the claim of molecular tumor boards, can contribute to the individual selection of a suitable therapy strategy and, thus, establish the latest findings and developments for the benefit of patients in the clinic.

4. United States pubmed.ncbi.nlm.nih.gov

Belzutifan Plus Cabozantinib Is Effective in Immunotherapy-Treated Renal Cell Carcinoma. [2023] Belzutifan plus cabozantinib has antitumor activity in previously treated advanced clear cell renal cell carcinoma.

5. Spain pubmed.ncbi.nlm.nih.gov

[New treatments for renal carcinoma]. [2019] Renal cell carcinoma presents several unique features, which distinguish it from other tumours. The increase in survival that has been described in patients with renal cell carcinoma following nephrectomy breaks a classical rule of oncology, which states that surgery of the primary tumour has no role in the treatment of patients with advanced disease. Together with melanoma, it is the only tumour in which immunomodulatory treatments with drugs such as interleukin-2 produces a clinical benefit to patients. In randomized trials treatment of metastatic renal cell carcinoma with high dose interleukin-2 has confirmed its ability to induce long-term complete responses, which in practice can be considered equivalent to cure. Lastly, renal cell carcinoma is being used as a clinical model to demonstrate the role of several targeted treatments, with over 30 novel agents under development. It has been the first tumour type in which treatment with angiogenesis inhibitors has shown a clinical benefit. This article reviews the most relevant aspects of renal cell carcinoma, including epidemiology, prognostic factors, clinical presentation, molecular bases and the current status of development of the most relevant novel treatments for this disease.