Cabozantinib + Nivolumab for Cancer in HIV Patients

Not currently recruiting at 4 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the side effects of two drugs, cabozantinib and nivolumab, in people with advanced cancer who are also undergoing HIV treatment. Cabozantinib blocks enzymes that help tumor cells grow, while nivolumab is an immunotherapy that aids the immune system in attacking cancer cells. The goal is to determine if these drugs can shrink or stabilize tumors in people with HIV. This trial might suit someone with advanced cancer, receiving HIV treatment, and willing to try a new combination of therapies. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering a chance to be among the first to receive this combination therapy.

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.

Is there any evidence suggesting that cabozantinib and nivolumab are likely to be safe for humans?

Research has shown that cabozantinib and nivolumab have been tested for safety in people with various types of cancer, including those with HIV. Some studies found that using these two drugs together can cause liver problems, with more significant increases in liver enzymes than when using nivolumab alone. However, other research suggests that treatments like nivolumab, which help the immune system fight cancer, are generally safe for people with HIV.

This trial is in the early stages, so researchers are still assessing how well people can tolerate the combination. Past studies suggest potential side effects, but they also show promise in fighting cancer. Prospective participants should consider this information carefully. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of cabozantinib and nivolumab for cancer in HIV patients because it offers a unique approach compared to traditional treatments. Unlike standard therapies, which often focus solely on targeting cancer cells, this combination enhances the immune system's ability to fight cancer through nivolumab's checkpoint inhibition and cabozantinib's inhibition of tumor growth and spread. This dual-action approach could potentially lead to more effective management of cancer in patients who are also living with HIV, a group that often faces limited treatment options.

What evidence suggests that cabozantinib and nivolumab might be effective for advanced cancer in HIV patients?

Research shows that using cabozantinib and nivolumab together, as studied in this trial, may help treat different types of cancer. Studies have found that this combination can shrink or stop tumor growth, even in patients with HIV. In some cases, the benefits of using cabozantinib with nivolumab lasted for several years. Patients who tried this treatment experienced positive results, and it is considered as safe as using cabozantinib alone. These findings suggest that this treatment could effectively manage advanced cancers. ^{2 6 7 8 9}

Who Is on the Research Team?

Haiying Cheng

Principal Investigator

Albert Einstein College of Medicine EDDOP

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-05956

Testing the Combination of the Anti-cancer Drugs XL184 ... Giving cabozantinib and nivolumab may shrink or stabilize cancer in patients undergoing treatment for HIV.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9340935/

Cabozantinib combination therapy for the treatment of solid ... This review demonstrates the promising efficacy outcomes of cabozantinib combined with other therapies, and a safety profile similar to cabozantinib alone.

3. ir.exelixis.com ir.exelixis.com/news-releases/news-release-details/exelixis-announces-final-five-year-follow-results-checkmate-9er

9ER Trial Evaluating CABOMETYX® (cabozantinib ... - Exelixis After more than five years of follow-up, the findings demonstrated that efficacy benefits with CABOMETYX in combination with Opdivo were sustained long term.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03866382

Study Details | NCT03866382 | Testing the Effectiveness of ... Giving cabozantinib, nivolumab, and ipilimumab may work better in treating patients with genitourinary tumors that have no treatment options compared to giving ...

5. opdivohcp.com opdivohcp.com/efficacy/rcc/opdivo-cabometyx

OPDIVO® (nivolumab) + CABOMETYX® (cabozantinib ... In HCC patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 8% (4/49) of patients. In RCC patients ...

6. opdivohcp.com opdivohcp.com/safety/rcc/opdivo-cabometyx

OPDIVO® (nivolumab) + CABOMETYX® (cabozantinib) Safety ... OPDIVO in combination with cabozantinib can cause hepatic toxicity with higher frequencies of Grade 3 and 4 ALT and AST elevations compared to OPDIVO alone.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8467545/

Immune Checkpoint Inhibitors in People Living with HIV/AIDS Matching retrospectively reported evidence and Uldrik's prospective study, anti-PD1/PD-L1 therapy appears to be safe and effective in HIV patients with cancer.

8. withpower.com withpower.com/trial/phase-1-infections-10-2020-17b14

Cabozantinib + Nivolumab for Cancer in HIV Patients Research shows that Cabozantinib and Nivolumab have been studied for safety in various cancers, including in people living with HIV. Side effects were observed ...

9. ema.europa.eu ema.europa.eu/en/documents/product-information/cabometyx-epar-product-information_en.pdf

Cabometyx, INN-Cabozantinib - EMA Cabozantinib is not recommended for use in patients with severe renal impairment as safety and efficacy have not been established in this population. Hepatic ...