Cabozantinib + Nivolumab for Advanced Skin and Head & Neck Cancers

Recruiting at 244 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anticoagulants, Steroids, CYP3A4 inducers

Disqualifiers: Pregnancy, Organ dysfunction, Autoimmune disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 13

Duration: 2 years

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two drugs, cabozantinib (a cancer treatment that blocks growth enzymes) and nivolumab (an immunotherapy drug), in treating advanced melanoma or squamous cell carcinoma of the head and neck. The goal is to determine if these drugs can stop or shrink tumors by blocking growth enzymes and boosting the immune system to attack the cancer. The trial also examines whether certain biological markers (signs in the body indicating disease presence) influence patient response to treatment. Suitable participants have advanced melanoma or squamous cell carcinoma that has progressed despite previous treatment with PD-1 inhibitors. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to important advancements in cancer therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must not take certain medications like strong CYP3A4 inducers or inhibitors, and you should not be on anticoagulants like warfarin unless it's low-dose aspirin or specific other anticoagulants. It's best to discuss your current medications with the trial team.

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

Research has shown that the combination of cabozantinib and nivolumab has been tested for safety in people. In a study on advanced kidney cancer, this combination was generally well-tolerated, though some patients experienced side effects such as diarrhea, tiredness, and changes in liver function tests.

Nivolumab alone has also been tested in head and neck cancer and was found to be safe, although some people reported mild to moderate side effects like tiredness and skin rash.

This trial is in phase II, indicating that some safety information exists from earlier studies. However, more research is needed to fully understand all possible side effects when these drugs are used together. Prospective participants should discuss any concerns with the study team. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for advanced skin and head & neck cancers?

Researchers are excited about the combination of cabozantinib and nivolumab for advanced skin and head & neck cancers because it offers a novel approach to treatment. Unlike traditional therapies that might individually target tumor cells or boost the immune system, this combination leverages both strategies. Cabozantinib uniquely inhibits pathways that help cancer cells grow and spread, while nivolumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. This dual-action approach has the potential to be more effective than existing treatments, possibly leading to better outcomes for patients.

What evidence suggests that the combination of cabozantinib and nivolumab might be an effective treatment for advanced skin and head & neck cancers?

In this trial, participants will receive a combination of cabozantinib and nivolumab to treat advanced skin and head and neck cancers. Research has shown that using cabozantinib and nivolumab together may help treat advanced cancers. This combination has improved outcomes in some cancers, such as advanced kidney cancer. Nivolumab, a type of immunotherapy, helps the body's immune system fight cancer cells, while cabozantinib blocks enzymes that tumors need to grow. Some studies on head and neck cancer found that nivolumab alone can help patients who have already received other treatments. When used together, these drugs might more effectively stop cancer from growing or spreading. Although more research is needed, early results suggest they could benefit the treatment of advanced melanoma and head and neck cancers. ^{2 3 4 6 7}

Who Is on the Research Team?

Siwen Hu-Lieskovan

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

Adults with advanced melanoma or squamous cell head and neck cancer that has spread, who have progressed after PD-1 checkpoint therapy. They must be able to take oral medication, have measurable disease, known HPV/p16 status for oropharyngeal cancer, adequate organ function and performance status. Exclusions include prior anti-VEGF therapies, active autoimmune diseases requiring steroids, significant infections or organ dysfunction.

Inclusion Criteria

I haven't had serious heart problems in the last 3 months.

My organs function well enough for treatment.

I do not take steroids or other drugs for an autoimmune disease, with some exceptions.

Exclusion Criteria

Participants must not have received investigational agents or monoclonal antibodies within 28 days prior to step 2 registration

I haven't had cancer treatment or steroids in the last 14 days.

I haven't taken certain medications that affect enzyme levels recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

1 visit (in-person)

Treatment

Participants receive nivolumab intravenously and cabozantinib orally. Cycles repeat every 28 days for up to 2 years.

2 years

Monthly visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

3 years

Every 12 weeks for 1 year, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Cabozantinib S-malate
• Nivolumab

Trial Overview The trial is testing the combination of Cabozantinib (an enzyme blocker) and Nivolumab (an immunotherapy antibody) on patients with certain types of advanced cancers. It aims to see if these drugs can shrink or stabilize tumors based on biomarkers like 'tumor mutational burden' and 'tumor inflammation signature'.

How Is the Trial Designed?

Group I: Treatment (nivolumab and cabozantinib) Experimental Treatment 6 Interventions

Patients receive nivolumab IV over 30 minutes on day 1 of each cycle and cabozantinib PO daily. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans and collection of blood samples throughout the trial. Patients undergo a tumor biopsy during screening and optionally during follow-up.

Cabozantinib S-malate is already approved in United States, European Union for the following indications:

Approved in United States as Cabometyx for:

• Advanced renal cell carcinoma (RCC)
• Hepatocellular carcinoma (HCC)
• Locally advanced or metastatic differentiated thyroid cancer (DTC)

Approved in United States as Cometriq for:

• Medullary thyroid cancer

Approved in European Union as Cabometyx for:

• Advanced renal cell carcinoma (RCC)
• Hepatocellular carcinoma (HCC)
• Locally advanced or metastatic differentiated thyroid cancer (DTC)

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 platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas involving 36 patients, both nivolumab and pembrolizumab showed effectiveness, with median overall survival of 16.9 months for nivolumab and 19.2 months for pembrolizumab, indicating similar efficacy between the two treatments.

The median progression-free survival was 4.8 months for nivolumab and 9.3 months for pembrolizumab, with objective response rates of 38% and 47%, respectively, suggesting that both drugs are viable options for treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Yamashita, G., Okamoto, I., Ito, T., et al.[2023]

In a study involving 882 participants with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), pembrolizumab alone significantly improved overall survival compared to cetuximab with chemotherapy, especially in patients with high PD-L1 expression (CPS of 20 or more).

Pembrolizumab combined with chemotherapy also showed improved overall survival compared to cetuximab with chemotherapy across all populations, indicating that pembrolizumab is an effective first-line treatment option for HNSCC, particularly for those with PD-L1 positivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Burtness, B., Harrington, KJ., Greil, R., et al.[2021]

Chemotherapy remains the primary treatment for recurrent and metastatic head and neck squamous cell carcinoma, with the current standard being a combination of cisplatin, 5-fluorouracil, and cetuximab for fit patients.

Immunotherapy options like nivolumab and pembrolizumab have become new standards in second-line treatment, showing improved overall survival, but further research is needed to identify predictive markers for patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy for recurrent/metastatic head and neck cancers. Karabajakian, A., Toussaint, P., Neidhardt, EM., et al.[2019]

In a real-world analysis of adverse events from two combination therapies for advanced renal cell carcinoma, cabozantinib (CAB) plus nivolumab (NIVO) showed higher incidence rates of seven types of toxicities compared to ipilimumab (IPI) plus NIVO.

Conversely, IPI + NIVO was associated with higher rates of three types of toxicities and had a greater incidence of serious adverse events, suggesting that both therapies have distinct safety profiles that can guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. Blas, L., Shiota, M., Tsukahara, S., 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]

In a phase 3 trial involving 855 patients with untreated advanced renal-cell carcinoma, the combination of cabozantinib with nivolumab and ipilimumab significantly improved progression-free survival compared to nivolumab and ipilimumab alone, with a 12-month progression-free survival rate of 57% versus 49%.

However, the experimental group experienced a higher incidence of severe adverse events (grade 3 or 4) at 79%, compared to 56% in the control group, indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. Choueiri, TK., Powles, T., Albiges, L., et al.[2023]

Nivolumab, a PD-1 inhibitor, has been FDA-approved for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) after platinum-based therapy, but treatment options remain limited for these patients.

A case study of a 46-year-old male with refractory HNSCC showed successful treatment using a combination of nivolumab and ipilimumab, suggesting potential efficacy for this combination therapy in HNSCC, similar to its success in metastatic melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of Refractory Squamous Cell Cancer of the Head and Neck with Nivolumab and Ipilimumab. Schwab, KS., Kristiansen, G., Schild, HH., et al.[2022]

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 study of 14 heavily pretreated patients with recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC), the combination of pembrolizumab and lenvatinib showed an objective response rate of 28.6%, indicating potential efficacy even in patients who had previously failed anti-PD-1 therapy.

The disease control rate was 42.9%, with an overall survival of 6.2 months and progression-free survival of 4.6 months, suggesting that this combination therapy may provide meaningful benefits for patients who have limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of pembrolizumab and lenvatinib is a potential treatment option for heavily pretreated recurrent and metastatic head and neck cancer. Chen, TH., Chang, PM., Yang, MH.[2021]

The combination of cabozantinib (a tyrosine kinase inhibitor) and nivolumab (an immune checkpoint inhibitor) significantly improved progression-free survival, overall survival, and objective response rates in patients with untreated advanced renal cell carcinoma compared to sunitinib, supporting its approval as a first-line therapy.

While the safety profile of the combination treatment is generally manageable, it requires careful monitoring and management of overlapping adverse events, such as diarrhea and hepatotoxicity, to maintain patient tolerability and treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of adverse events associated with cabozantinib plus nivolumab in renal cell carcinoma: A review. McGregor, B., Mortazavi, A., Cordes, L., et al.[2023]

Citations

1. clinicaltrials.icts.uci.edu clinicaltrials.icts.uci.edu/trial/NCT05136196

UC Irvine Skin Cancer/Melanoma Trial → BiCaZO: A Study ... This phase II trial studies the good and bad effects of the combination of drugs called cabozantinib and nivolumab in treating patients with melanoma or ...

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

OPDIVO® (nivolumab) + CABOMETYX® (cabozantinib ... Find efficacy information for OPDIVO® (nivolumab) + CABOMETYX® (cabozantinib) in aRCC. Please see Indications and Important Safety Information.

3. withpower.com withpower.com/trial/phase-2-melanoma-1-2022-2323e

Cabozantinib + Nivolumab for Advanced Skin and Head & ... This phase II trial studies the good and bad effects of the combination of drugs called cabozantinib and nivolumab in treating patients with melanoma or ...

4. mayo.edu mayo.edu/research/clinical-trials/cls-20545053

Clinical Trials - BiCaZO BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an ...

5. opdivo.com opdivo.com/head-and-neck-cancer/clinical-trial-results

Clinical trial results for previously treated head and neck ... See how OPDIVO® (nivolumab) performed in clinical trials for certain adults with previously treated squamous cell head and neck cancer (SCCHN).

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05136196

NCT05136196 | BiCaZO: A Study Combining Two ... This phase II trial studies the good and bad effects of the combination of drugs called cabozantinib and nivolumab in treating patients with melanoma or ...

7. masseycancercenter.org masseycancercenter.org/clinical-trials/details/biomarker-stratified-cabozantinib-nsc

Biomarker Stratified CaboZantinib (NSC#761968) and ... Biomarker Stratified CaboZantinib (NSC#761968) and NivOlumab ... Participants must have histologically confirmed squamous cell carcinoma of the head and neck ...