Durvalumab + Tremelimumab for Rare Cancers

Overseen By Jan Kueber, RN, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Prisma Health-Upstate

Must not be taking: Checkpoint inhibitors, Steroids

Disqualifiers: Autoimmune disease, CNS metastases, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, durvalumab and tremelimumab, to evaluate their effectiveness on certain rare advanced solid tumors. Researchers aim to understand how these treatments combat cancer and assess their safety and tolerability for patients. Participants should have a rare advanced cancer and must have tried or been unable to try standard treatments. Those diagnosed with a rare solid tumor and limited treatment options may find this trial suitable. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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, but you must not have had chemotherapy or certain steroids within 28 days before starting the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that using durvalumab and tremelimumab together is generally well tolerated. In one study, most participants (77.8%) experienced some side effects. More serious side effects were less common, occurring in 29.3% of participants, and 13.3% had to stop treatment due to severe reactions.

Another study found that this combination of treatments was safe and well-tolerated overall. Durvalumab aids the immune system in identifying cancer cells by blocking a protein called PD-L1, which cancer cells use to hide. Tremelimumab blocks another protein, CTLA-4, which can slow the immune system's response to cancer.

These studies provide strong evidence that the combination can be safely used in humans, but it is important to be aware of possible side effects, as with any treatment. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for rare cancers?

Researchers are excited about Durvalumab and Tremelimumab because they offer a novel approach to treating rare cancers through immune system activation. Unlike standard treatments that might only target cancer cells directly, these drugs are immune checkpoint inhibitors, which enhance the body's immune response against cancer. Durvalumab blocks the PD-L1 protein, while Tremelimumab targets CTLA-4, a different checkpoint, potentially leading to a more robust immune attack on tumors. This dual action could provide new hope for patients with rare cancers, potentially offering effectiveness where other treatments fall short.

What evidence suggests that durvalumab and tremelimumab might be an effective treatment for rare cancers?

Research has shown that using durvalumab and tremelimumab together may help treat certain cancers. In one study, 23 out of 36 patients responded well to this combination. Another study found it effective for specific cancers, such as salivary gland cancer. This suggests the treatment could be useful when other options are limited. Overall, these findings indicate that durvalumab and tremelimumab could help manage advanced rare solid tumors. Participants in this trial will receive this combination treatment to further evaluate its effectiveness. ^{3 6 7 8 9}

Who Is on the Research Team?

William J Edenfield, MD

Principal Investigator

Prisma Health-Upstate

Are You a Good Fit for This Trial?

This trial is for adults with rare advanced solid tumors who've had no luck with standard treatments or can't receive them. They should be relatively active (ECOG 0-2), able to undergo a tumor biopsy, and have their major organs functioning well. People who've previously used durvalumab, tremelimumab, or similar drugs; those with untreated brain metastases; recent steroid users; and patients with certain autoimmune diseases or other specific cancers under study elsewhere are excluded.

Inclusion Criteria

You are expected to live for at least 3 more months.

My blood, liver, and kidney functions are within normal ranges required for the trial.

Standard treatments have not worked for me or I was not eligible for them.

Exclusion Criteria

I haven't had chemotherapy in the last 4 weeks.

My cancer has spread to my brain and has not been treated.

I have had an autoimmune disease in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Exploration

Completed phase to explore dosing across a range of tumor types

Not specified

Dose-Expansion

Ongoing phase including certain soft tissue sarcomas, neuroendocrine tumors, and thymic carcinoma

24 months

13 doses of Durvalumab, 1 dose of Tremelimumab

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab and Tremelimumab

Trial Overview The trial is testing the combination of two drugs: Durvalumab and Tremelimumab in people with rare types of cancer that have spread. It's an open-label study where everyone knows what treatment they're getting, aiming to see how effective this drug combo is at fighting these cancers while also monitoring safety and side effects.

How Is the Trial Designed?

Group I: Single Arm Experimental Treatment 2 Interventions

Durvalumab, 1500 mg Q4W (equivalent to 20 mg/kg Q4W) intravenously for 13 doses and Tremelimumab 300mg intravenously as a single dose on cycle 1 day 1 only.

Who Is Running the Clinical Trial?

Prisma Health-Upstate

Lead Sponsor

Trials

91

Recruited

47,500+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

MedImmune LLC

Industry Sponsor

Trials

348

Recruited

788,000+

Founded

1988

Headquarters

Gaithersburg, USA

Known For

Biologics research

Top Products

Synagis, FluMist

Dr. Reginald Seeto

MedImmune LLC

Chief Medical Officer since 2008

MD from University of Sydney, B.Sc. from University of Sydney

Peter Greenleaf

MedImmune LLC

Chief Executive Officer since 2006

MBA from St. Joseph’s University, B.S. from Western Connecticut State University

Published Research Related to This Trial

In a phase 1b study involving 78 patients with advanced non-small cell lung cancer (NSCLC) who had previously failed PD-(L)1 therapy, the combination of durvalumab and tremelimumab showed a manageable safety profile, with common side effects including fatigue and diarrhea.

However, the treatment demonstrated limited efficacy, with an objective response rate of only 5.3% in PD-(L)1-refractory patients and 0% in PD-(L)1-relapsed patients, indicating that this combination may not be effective after PD-(L)1 treatment failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief Report: Safety and Antitumor Activity of Durvalumab Plus Tremelimumab in Programmed Cell Death-(Ligand)1-Monotherapy Pretreated, Advanced NSCLC: Results From a Phase 1b Clinical Trial. Garon, EB., Spira, AI., Goldberg, SB., et al.[2023]

In the phase 3 POSEIDON study involving 1013 treatment-naïve patients with metastatic non-small-cell lung cancer (NSCLC), the combination of tremelimumab, durvalumab, and chemotherapy significantly improved overall survival and progression-free survival compared to chemotherapy alone.

Patients receiving the combination treatment also experienced a longer time to deterioration in quality of life and various symptoms, indicating better overall health status compared to those on chemotherapy, supporting its use as a first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with durvalumab, with or without tremelimumab, plus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (POSEIDON). Garon, EB., Cho, BC., Luft, A., et al.[2023]

Durvalumab, an immunotherapy drug for non-small cell lung cancer (NSCLC), has shown significant activity and acceptable tolerability, especially in patients with at least 25% PD-L1 tumor expression, and has been established as a standard treatment following chemoradiation based on the PACIFIC study results.

While durvalumab is effective in wild-type EGFR and ALK patients, its efficacy is lower in those with EGFR mutations or ALK-positive status, highlighting the need for ongoing research into combination therapies and the management of treatment-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. Mezquita, L., Planchard, D.[2019]

In the phase III POSEIDON study involving 1,013 patients with metastatic non-small-cell lung cancer (mNSCLC), the combination of durvalumab plus chemotherapy significantly improved progression-free survival (PFS) compared to chemotherapy alone, with a median PFS of 5.5 months versus 4.8 months.

The addition of tremelimumab to durvalumab and chemotherapy further enhanced both PFS and overall survival (OS) compared to chemotherapy alone, with a median OS of 14.0 months versus 11.7 months, while maintaining a similar safety profile to chemotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study. Johnson, ML., Cho, BC., Luft, A., et al.[2023]

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

The combination of durvalumab and tremelimumab showed improved disease control rates in patients with head and neck squamous cell carcinoma compared to tremelimumab alone, indicating its potential efficacy in this cancer type.

The combination therapy had a tolerable safety profile, with no significant increase in treatment-related adverse events compared to monotherapy, suggesting it is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab and tremelimumab combination therapy versus durvalumab or tremelimumab monotherapy for patients with solid tumors: A systematic review and meta-analysis. Wang, BC., Li, PC., Fan, JQ., et al.[2022]

In a phase I trial involving Japanese patients with advanced cancer, tremelimumab was found to be safe and well-tolerated, with no dose-limiting toxicities observed in the initial dosing phase, although 75% of patients reported treatment-related adverse events.

When combined with durvalumab, tremelimumab showed a manageable safety profile, with only two instances of serious adverse events (Grade 4 myasthenia gravis and hyperglycemia), indicating that the combination therapy can be administered with careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Tremelimumab Monotherapy or in Combination With Durvalumab in Japanese Patients With Advanced Solid Tumors or Malignant Mesothelioma. Fujiwara, Y., Takahashi, Y., Okada, M., et al.[2022]

This phase II study aims to evaluate the effectiveness of combining durvalumab and tremelimumab with neoadjuvant chemotherapy in improving progression-free survival (PFS) in patients with advanced-stage ovarian cancer, specifically those with stage IIIC/IV epithelial ovarian cancer.

The study will involve 24 patients and will assess immune biomarkers and changes in the tumor microenvironment through serial biopsies, with the primary goal of achieving a 12-month PFS rate, while also monitoring safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of neoadjuvant chemotherapy plus durvalumab and tremelimumab in advanced-stage ovarian cancer: a Korean Gynecologic Oncology Group Study (KGOG 3046), TRU-D. Lee, JY., Kim, JW., Lim, MC., et al.[2020]

In the NEPTUNE phase 3 study involving 823 patients with metastatic non-small cell lung cancer (mNSCLC), the combination of durvalumab and tremelimumab did not significantly improve overall survival compared to standard chemotherapy in patients with a blood tumor mutational burden (bTMB) of 20 mutations per megabase or more.

However, the combination therapy showed a lower incidence of severe treatment-related adverse events (20.7%) compared to chemotherapy (33.6%), suggesting a potentially better safety profile for durvalumab plus tremelimumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NEPTUNE: Phase 3 Study of First-Line Durvalumab Plus Tremelimumab in Patients With Metastatic NSCLC. de Castro, G., Rizvi, NA., Schmid, P., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33893692/

A Phase II Study of Durvalumab in Combination with ... Conclusion: This single-cohort basket trial demonstrated clinical activity from combined checkpoint blockade in 23 of the 36 evaluable patients. Patients with ...

2. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00570-4/fulltext

a multi-centre, non-blinded, open-label phase II basket trial Durvalumab + tremelimumab treatment resulted in meaningful responses in salivary carcinoma and CCCO and deserves further exploration in front-line studies.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02938793

Durvalumab in Combination With Tremelimumab ... Study Plan ; Antitumor Activity, To evaluate the antitumor activity of durvalumab in combination with tremelimumab based on immune-related Response Evaluation ...

4. esmoopen.com esmoopen.com/article/S2059-7029(25)00927-5/fulltext

outcomes by tumor mutational burden in POSEIDON Tremelimumab plus durvalumab and chemotherapy (T + D + CT) showed durable long-term overall survival (OS) benefit versus CT alone in first-line metastatic non- ...

5. onclive.com onclive.com/view/durvalumab-plus-tremelimumab-and-trastuzumab-yields-clinical-activity-in-trastuzumab-resistant-her2-breast-cancer

Durvalumab Plus Tremelimumab and Trastuzumab Yields ... Patients with HER2-positive, ER-negative disease treated in cohort 2 (n = 23) experienced an ORR of 8.7% (95% CI, 2%-30%) and a 12-month PFS ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10501063/

Adverse events induced by durvalumab and tremelimumab ... The data revealed the occurrence of AEs (77.8%), grade ⩾ 3 AEs (29.3%), serious AEs (34.9%), AEs resulting in treatment discontinuation (13.3%), ...

7. esmoopen.com esmoopen.com/article/S2059-7029(24)01415-7/fulltext

Safety and clinical activity of durvalumab combined with ... In this phase I study, durvalumab, a PD-L1 inhibitor, plus tremelimumab, a CTLA-4 inhibitor, was well tolerated and safe.

8. sciencedirect.com sciencedirect.com/science/article/pii/S2589537024005704

a multi-centre, non-blinded, open-label phase II basket trial Durvalumab + tremelimumab treatment resulted in meaningful responses in salivary carcinoma and CCCO and deserves further exploration in front-line studies.

9. jitc.bmj.com jitc.bmj.com/content/13/5/e011140.full

Differential safety profiles of durvalumab monotherapy and ... We retrospectively analyzed pan-tumor pooled safety data from phase I to III clinical trials of patients with advanced cancers who received durvalumab ...