Atezolizumab + Cabozantinib for Pancreatic Cancer

Overseen By Prisca Zimmerman

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Arizona

Must not be taking: Anticoagulants, Immunosuppressants

Disqualifiers: Brain metastases, 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: 21

Duration: 6 months

29 Participants Needed

Trial Summary

What is the purpose of this trial?

Pancreatic cancer is one of the leading causes of cancer deaths in the United States with limited treatment options, especially for those patients with metastatic disease. Combination treatment with cabozantinib and atezolizumab, has demonstrated safety for the treatment of other cancers and has shown promise in preclinical studies utilizing patient derived pancreas organoids. In this study, patients with refractory, metastatic pancreatic cancer will receive combination cabozantinib + atezolizumab and the efficacy of this treatment will be assessed through overall response rate (ORR), disease control rate (DCR), median overall survival (mOS), and median progression free survival (mPFS). Safety and tolerability of combination cabozantinib plus atezolizumab in metastatic pancreatic cancer patients will also be assessed and immune profiling pre- and post-treatment will be explored.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have received certain treatments like small molecule kinase inhibitors, cytotoxic, biologic, or other systemic anticancer therapies within 2-4 weeks before starting the study treatment. It's best to discuss your current medications with the trial team to ensure eligibility.

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

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like specific anticoagulants and immunosuppressive drugs are restricted, so it's best to discuss your current medications with the study team.

What data supports the idea that Atezolizumab + Cabozantinib for Pancreatic Cancer is an effective drug?

The available research does not provide specific data on the effectiveness of Atezolizumab + Cabozantinib for pancreatic cancer. Instead, it discusses other treatments and approaches, such as gemcitabine, multi-kinase inhibitors, and novel therapies targeting specific genetic changes in pancreatic cancer. These treatments have shown some promise in clinical trials, but there is no direct mention of Atezolizumab + Cabozantinib in the context of pancreatic cancer in the provided information. ^{1 2 3 4 5}

What safety data exists for Atezolizumab and Cabozantinib treatment?

Atezolizumab, also known as Tecentriq, has been evaluated for safety in various cancers, including bladder cancer, non-small cell lung cancer, and breast cancer. Common adverse reactions include fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation. Grade 3 to 4 adverse events include dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, and musculoskeletal pain. Immune-related adverse events include pneumonitis, hepatitis, colitis, and thyroid disease. The safety profile is considered acceptable, with manageable side effects. However, specific safety data for the combination of Atezolizumab and Cabozantinib in pancreatic cancer is not detailed in the provided research. ^{6 7 8 9 10}

Is the combination of Atezolizumab and Cabozantinib generally safe for humans?

Atezolizumab, also known as Tecentriq, has been used in various cancers like bladder, lung, and breast cancer, showing a generally acceptable safety profile. Common side effects include fatigue, decreased appetite, and nausea, while more serious effects can include lung inflammation and liver issues. Cabozantinib, known as Cabometyx, is also used in cancer treatment, but specific safety data for the combination with Atezolizumab in pancreatic cancer is not detailed in the provided research. ^{6 7 8 9 10}

Is the drug Atezolizumab, Cabozantinib a promising treatment for pancreatic cancer?

Atezolizumab, known as Tecentriq, is a drug that helps the immune system fight cancer by blocking a protein that stops immune cells from attacking cancer cells. It has shown promise in treating other types of cancer, like bladder and lung cancer, by improving survival rates and response to treatment. While specific results for pancreatic cancer aren't provided, its success in other cancers suggests it could be promising for pancreatic cancer as well. ^{7 9 11 12 13}

What makes the drug combination of Atezolizumab and Cabozantinib unique for pancreatic cancer?

The combination of Atezolizumab and Cabozantinib is unique because Atezolizumab is an immune checkpoint inhibitor that enhances the body's immune response against cancer cells, while Cabozantinib targets multiple pathways involved in tumor growth and spread. This dual approach may offer a novel way to treat pancreatic cancer, which currently has limited effective treatment options. ^{7 9 11 12 13}

Research Team

Rachna Shroff, M.D.

Principal Investigator

University of Arizona

Eligibility Criteria

Adults over 18 with stage IV pancreatic adenocarcinoma that has spread and is resistant to certain chemotherapies. They must have measurable disease, be in good physical condition (ECOG ≤1), and recovered from previous treatments' side effects. Participants need functioning organs/marrow, can't be pregnant or breastfeeding, must use contraception, and not have had specific prior treatments like cabozantinib or immune therapies.

Inclusion Criteria

I am fully active and can carry on all my pre-disease activities without restriction.

I have recovered from side effects of previous treatments, with only mild symptoms remaining.

It has been over two weeks since my last cancer treatment.

Exclusion Criteria

I have previously been treated with specific immune therapies.

I haven't taken any kinase inhibitor medication in the last 28 days.

I have pain from my cancer that isn't relieved by treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination cabozantinib and atezolizumab. Cabozantinib 40 mg is administered orally once daily, and Atezolizumab 1200 mg is administered intravenously on Day 1 of every 21-day cycle.

6 months

Every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including immune profiling and tumor response evaluation.

4 weeks

Long-term follow-up

Participants are assessed for survival outcomes and disease progression.

Up to 100 months

Treatment Details

Interventions

• Atezolizumab
• Cabozantinib

Trial Overview The trial tests a combination of Cabozantinib + Atezolizumab for metastatic pancreatic cancer patients who haven't responded to standard treatments. It measures how well the treatment works (response rate), controls the disease, extends life without progression, overall survival time, safety/tolerability and examines immune changes before/after treatment.

Participant Groups

Group I: Cabozantinib 40mg + Atezolizumab 1200mg Experimental Treatment 1 Intervention

Cabozantinib 40 mg, tablets, oral administration, once daily, continuously. Atezolizumab 1200 mg, administered intravenously, on Day 1 of every 21 day cycle.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

University of Arizona

Lead Sponsor

Trials

545

Recruited

161,000+

Findings from Research

Fewer than 20% of pancreatic cancer patients have tumors confined to the pancreas, highlighting the need for effective treatment strategies for advanced disease, as about 40% present with locally advanced cancer.

Gemcitabine is established as the first-line treatment for pancreatic cancer, showing significant clinical benefits, and is being explored in combination with various other agents like 5-fluorouracil and irinotecan to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future directions in the treatment of pancreatic cancer. Haller, DG.[2022]

Itacitinib, a selective JAK1 inhibitor, combined with nab-paclitaxel and gemcitabine, showed an acceptable safety profile and clinical activity in patients with advanced solid tumors, including pancreatic cancer, with a 24% overall response rate across various doses.

The study indicated that while itacitinib was tolerated at lower doses, treatment-related toxicities such as neutropenia and fatigue were common, leading to dose adjustments; however, the study was terminated early due to negative results from a related phase III trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors. Beatty, GL., Shahda, S., Beck, T., et al.[2022]

Novel multi-kinase inhibitor drug combinations, including sorafenib, regorafenib, and neratinib, have shown promise in treating pancreatic cancer, demonstrating objective anti-tumor responses in clinical settings.

These multi-kinase inhibitors have been safely translated from laboratory research to clinical use, suggesting a potential shift away from traditional cytotoxic chemotherapy for this challenging malignancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The development of multi-kinase inhibitors as pancreatic cancer therapeutics. Dent, P., Poklepovic, A., Booth, L., et al.[2022]

Recent advances in targeted therapy and immunotherapy show promise for treating pancreatic ductal adenocarcinoma (PDAC), which is often diagnosed at advanced stages and has limited treatment options.

Combining these new therapies may enhance treatment effectiveness and improve patient outcomes, as supported by current preclinical and clinical evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translational advances in pancreatic ductal adenocarcinoma therapy. Hosein, AN., Dougan, SK., Aguirre, AJ., et al.[2023]

Cytotoxic chemotherapy, particularly the mFOLFIRINOX regimen, remains the standard treatment for resectable pancreatic ductal adenocarcinoma (PDAC), but neoadjuvant strategies are showing improved outcomes in clinical trials.

Novel therapies targeting specific genetic alterations, such as BRCA1/2 mutations and MMR deficiencies, have demonstrated significant efficacy in clinical trials, leading to FDA approvals for drugs like larotrectinib and pembrolizumab, which can be used regardless of the tumor's origin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From state-of-the-art treatments to novel therapies for advanced-stage pancreatic cancer. Nevala-Plagemann, C., Hidalgo, M., Garrido-Laguna, I.[2023]

Atezolizumab, the first anti-PD-L1 monoclonal antibody approved by the FDA, has shown promising efficacy in treating metastatic triple-negative breast cancer, supported by data from the Phase III IMpassion130 trial.

The review highlights the pharmacodynamic and pharmacokinetic properties of atezolizumab, emphasizing its safety and effectiveness in various cancers, including small-cell lung cancer and renal cell cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. Mavratzas, A., Seitz, J., Smetanay, K., et al.[2020]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

In a study of 115 patients with metastatic urothelial carcinoma treated with atezolizumab (ATZ) after failing first-line chemotherapy, the objective response rate was 28.7%, indicating that ATZ is effective in this patient population.

The treatment was well tolerated, with 98% of patients experiencing adverse events, but only 21.2% had severe (grade 3-4) treatment-related adverse events, suggesting a manageable safety profile similar to previous clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences. Tural, D., Ölmez, ÖF., Sümbül, AT., et al.[2022]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

Atezolizumab significantly improves overall survival in patients with metastatic non-small cell lung cancer (mNSCLC), with median survival times of 13.8 months in the atezolizumab group compared to 9.6 months in the docetaxel group in the OAK trial.

The treatment has an acceptable safety profile, with common side effects including fatigue and decreased appetite, and serious immune-related adverse events occurring in a small percentage of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. Weinstock, C., Khozin, S., Suzman, D., et al.[2022]

Atezolizumab, a monoclonal antibody targeting PD-L1, shows promising efficacy in treating metastatic colorectal cancer (mCRC), particularly in patients with deficient mismatch repair (dMMR), indicating a potential new treatment avenue for this subgroup.

Ongoing clinical trials suggest that atezolizumab may be even more effective when combined with chemotherapy or targeted therapies, such as the MEK inhibitor cobimetinib, paving the way for its inclusion in future treatment protocols for mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for the treatment of colorectal cancer: the latest evidence and clinical potential. Tapia Rico, G., Price, TJ.[2022]

Atezolizumab is being studied as a neoadjuvant treatment for muscle-invasive bladder cancer (MIBC) in a phase II trial, where it is administered before radical cystectomy to evaluate its effectiveness based on the BASQ classification of tumor subtypes.

The trial aims to determine the objective pathological responses and 1-year progression-free survival rates in patients with MIBC, highlighting the potential of using molecular subtype characteristics to select the most responsive patient groups for atezolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of neoadjuvant atezolizumab treatment in patients with advanced urothelial bladder cancer according to the BASQ classification: a study protocol for an open-label, two-cohort, phase II trial. Yuk, HD., Jeong, CW., Kwak, C., et al.[2021]

Atezolizumab shows consistent pharmacokinetics across various tumor types and treatment settings, whether used alone or in combination, supporting its flexible dosing regimens of 840 mg every 2 weeks, 1200 mg every 3 weeks, and 1680 mg every 4 weeks.

The efficacy of atezolizumab in combination therapies was found to be independent of drug exposure levels, and there was no significant increase in adverse events with higher doses, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extension of the Alternative Intravenous Dosing Regimens of Atezolizumab into Combination Settings through Modeling and Simulation. Liu, SN., Marchand, M., Liu, X., et al.[2022]

References

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

Future directions in the treatment of pancreatic cancer. [2022]

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

A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors. [2022]

3. England pubmed.ncbi.nlm.nih.gov

The development of multi-kinase inhibitors as pancreatic cancer therapeutics. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Translational advances in pancreatic ductal adenocarcinoma therapy. [2023]

5. England pubmed.ncbi.nlm.nih.gov

From state-of-the-art treatments to novel therapies for advanced-stage pancreatic cancer. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. [2020]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. [2019]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences. [2022]

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

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

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

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Atezolizumab for the treatment of colorectal cancer: the latest evidence and clinical potential. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Efficacy of neoadjuvant atezolizumab treatment in patients with advanced urothelial bladder cancer according to the BASQ classification: a study protocol for an open-label, two-cohort, phase II trial. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Extension of the Alternative Intravenous Dosing Regimens of Atezolizumab into Combination Settings through Modeling and Simulation. [2022]