Cabozantinib + Nivolumab for Cancer in HIV Patients

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must be taking: Antiretrovirals

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Autoimmune disease, Brain metastases, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 1 year

18 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but it does require that your HIV treatment be adjusted if it includes certain drugs that interact with the trial medications. Specifically, you cannot be on potent CYP3A4-inhibiting agents, and your antiretroviral therapy must be stable for at least 4 weeks before starting the trial.

What data supports the effectiveness of the drug combination Cabozantinib and Nivolumab for cancer in HIV patients?

Research shows that Cabozantinib and Nivolumab have been effective in treating various types of cancer, such as renal cell carcinoma and urothelial carcinoma, in other patient groups. This suggests potential benefits for HIV patients with cancer, although specific data for this group is limited. ^{1 2 3 4 5}

Is the combination of Cabozantinib and Nivolumab safe for HIV patients with cancer?

Research shows that Cabozantinib and Nivolumab have been studied for safety in various cancers, including in people living with HIV. Side effects were observed in some patients, but they were generally manageable, and the treatment did not negatively affect HIV markers like CD4 counts or viral load. ^{1 2 4 5 6}

How is the drug combination of Cabozantinib and Nivolumab unique for treating cancer in HIV patients?

This drug combination is unique because it combines Cabozantinib, which targets multiple pathways involved in cancer growth, with Nivolumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. This approach is novel for HIV patients with cancer, as it considers the interaction with antiretroviral therapy, which is crucial for this population. ^{1 2 5 7 8}

What is the purpose of this trial?

This phase I trial investigates the side effects of cabozantinib and nivolumab in treating patients with cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and who are undergoing treatment for human immunodeficiency virus (HIV). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib and nivolumab may shrink or stabilize cancer in patients undergoing treatment for HIV.

Research Team

Haiying Cheng

Principal Investigator

Albert Einstein College of Medicine EDDOP

Eligibility Criteria

This trial is for adults with advanced cancers that have spread and are also undergoing treatment for HIV. They must meet certain lab criteria, not be pregnant or breastfeeding, use contraception, and have a life expectancy of at least 12 weeks. People with autoimmune diseases, recent chemotherapy or radiation therapy, allergies to similar drugs, or taking strong CYP3A4 inhibitors can't join.

Inclusion Criteria

My advanced cancer has returned or spread and needs treatment that could include XL184 (cabozantinib) or nivolumab.

I have HIV and am receiving treatment for it.

Your blood test results for certain things like white blood cells, platelets, liver function, kidney function, and immune system cells must meet certain levels.

Exclusion Criteria

I have previously taken XL184, PD-1/PD-L1 inhibitors, or VEGFR inhibitors.

Subjects who are receiving any other investigational agents

I haven't had major surgery recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cabozantinib s-malate orally once daily and nivolumab intravenously on day 1 of each 28-day cycle, repeated for up to 1 year or until a response is achieved

Up to 1 year

Monthly visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

16 weeks

Regular follow-up visits for imaging and blood sample collection

Treatment Details

Interventions

• Cabozantinib
• Nivolumab

Trial Overview The trial tests the combination of cabozantinib (which blocks enzymes needed for cancer cell growth) and nivolumab (an immunotherapy drug helping the immune system attack cancer). It aims to see if this combo can shrink or stabilize various advanced cancers in patients who are also being treated for HIV.

Participant Groups

Group I: Treatment (cabozantinib s-malate, nivolumab) Experimental Treatment 5 Interventions

Patients receive cabozantinib s-malate PO QD on days 1-28 of each cycle and nivolumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days for up to 1 year or 1 year after a partial response is achieved, or 6 months after a complete response is achieved in the absence of disease progression or unacceptable toxicity. Patients also undergo a CT scan and/or MRI as well as blood sample collection throughout the trial.

Cabozantinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in United States as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Canada as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Japan as Cabometyx for:

• Renal cell carcinoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 346 patients receiving cabozantinib (CABO) as second-line therapy after various first-line treatments, the median overall survival was 21.4 months for those who previously received ipilimumab-nivolumab (IPI-NIVO), indicating that CABO is effective regardless of the initial treatment.

The median time to treatment failure for CABO was 7.6 months, suggesting that it provides a clinically meaningful benefit as a second-line option after different first-line therapies, including immunotherapy and VEGF inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CABOSEQ: The Effectiveness of Cabozantinib in Patients With Treatment Refractory Advanced Renal Cell Carcinoma: Results From the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Navani, V., Wells, JC., Boyne, DJ., et al.[2023]

In a phase II trial involving 47 patients with advanced non-clear-cell renal cell carcinoma, the combination of cabozantinib and nivolumab showed a promising objective response rate of 47.5% in patients with papillary, unclassified, or translocation-associated RCC, along with a median progression-free survival of 12.5 months.

The treatment was less effective in chromophobe RCC, with no objective responses observed, highlighting the need for further research into genomic predictors of response, particularly mutations like NF2 and FH that were associated with better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates. Lee, CH., Voss, MH., Carlo, MI., et al.[2023]

Cabozantinib combined with nivolumab (CaboNivo) and with ipilimumab (CaboNivoIpi) showed manageable safety profiles, with 75% and 87% of patients experiencing grade 3 or 4 treatment-related adverse events, respectively, including fatigue and hypertension.

The treatment demonstrated promising efficacy, with an overall response rate of 30.6% and a median overall survival of 12.6 months for all patients, while patients with metastatic urothelial carcinoma had even better outcomes, with a median overall survival of 25.4 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced or Metastatic Urothelial Carcinoma and Other Genitourinary Tumors. Apolo, AB., Nadal, R., Girardi, DM., et al.[2023]

In a phase 3 trial involving 651 patients with untreated advanced renal-cell carcinoma, the combination of nivolumab and cabozantinib significantly improved progression-free survival (16.6 months) compared to sunitinib (8.3 months), with a hazard ratio of 0.51, indicating a 49% reduction in the risk of disease progression or death.

Patients receiving nivolumab plus cabozantinib also had a higher overall survival rate at 12 months (85.7%) compared to those on sunitinib (75.6%), and a greater objective response rate (55.7% vs. 27.1%), although adverse events were common in both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. Choueiri, TK., Powles, T., Burotto, M., et al.[2022]

The European Association of Urology now recommends nivolumab and cabozantinib as preferred treatments for patients with renal cancer who have not responded to previous vascular endothelial growth factor-targeted therapies.

Recent data indicate that cabozantinib offers a survival benefit, reinforcing its efficacy as a treatment option in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European Association of Urology Guidelines for Clear Cell Renal Cancers That Are Resistant to Vascular Endothelial Growth Factor Receptor-Targeted Therapy. Powles, T., Staehler, M., Ljungberg, B., et al.[2018]

References

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

CABOSEQ: The Effectiveness of Cabozantinib in Patients With Treatment Refractory Advanced Renal Cell Carcinoma: Results From the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). [2023]

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

Phase I trial of the multi-kinase inhibitor cabozantinib, a CYP3A4 substrate, plus CYP3A4 interacting antiretroviral therapy in people living HIV and cancer (AMC087). [2023]

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

Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates. [2023]

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

Phase I Study of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced or Metastatic Urothelial Carcinoma and Other Genitourinary Tumors. [2023]

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

Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. [2022]

6. Egypt pubmed.ncbi.nlm.nih.gov

Outcomes of Programmed Cell Death Protein 1 (PD-1) and Programmed Death-Ligand 1(PD-L1) Inhibitor Therapy in HIV Patients with Advanced Cancer. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Activity of cabozantinib after immune checkpoint blockade in metastatic clear-cell renal cell carcinoma. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

European Association of Urology Guidelines for Clear Cell Renal Cancers That Are Resistant to Vascular Endothelial Growth Factor Receptor-Targeted Therapy. [2018]