Durvalumab + Tremelimumab for Solid Tumors

Overseen By Heather Heath

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: John L. Villano, MD, PhD

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Autoimmune disorders, Active infection, Organ transplant, 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: Unknown

Duration: 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two immunotherapy drugs, Durvalumab and Tremelimumab, to determine if they slow the progression of certain solid tumors. The focus is on patients whose tumors have a moderate to high level of mutations, as these may respond better to this treatment. Suitable candidates have solid tumors that have not responded effectively to other specific types of immunotherapy. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you should not have received any anticancer therapy 30 days before starting the study drug. It's best to discuss your current medications with the study team to ensure they don't interfere with the trial.

Is there any evidence suggesting that the Durvalumab and Tremelimumab combination is likely to be safe for humans?

Research from previous studies shows that the combination of Durvalumab and Tremelimumab is generally safe for people, with a manageable safety profile. Most side effects were not severe and could be treated or managed by adjusting the dose.

However, some people did experience side effects. In one study, 77.8% of participants experienced some kind of unwanted effect from the treatment. About 29.3% had more serious side effects, known as grade 3 or higher. Serious side effects occurred in 34.9% of participants, and 13.3% had to stop treatment because of these effects.

Despite the possibility of side effects, these numbers suggest the treatment is relatively safe and well-tolerated for most people. It's important to consult with a doctor to understand how this might apply to individual cases. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for solid tumors?

Researchers are excited about Durvalumab and Tremelimumab because they offer a novel approach for treating solid tumors with a high tumor mutational burden. Unlike standard treatments, which often target specific proteins on cancer cells, this combination leverages the body's immune system by blocking two critical checkpoints: PD-L1 with Durvalumab and CTLA-4 with Tremelimumab. This dual blockade strategy can potentially enhance the immune response against cancer cells. This method is particularly promising for patients who have not responded well to traditional therapies and are seeking new hope through innovative immunotherapy options.

What evidence suggests that the Durvalumab and Tremelimumab combination might be an effective treatment for solid tumors?

Research has shown that using Durvalumab and Tremelimumab together can benefit patients with solid tumors. One study found that patients receiving this combination lived for a median of 11.5 months, compared to 8.7 months for those on a different treatment. This suggests the combination might extend life expectancy. Additional research indicates that this combo can delay tumor growth or spread, known as progression-free survival. These results are particularly promising for patients with a moderate to high level of tumor mutations, which can influence treatment effectiveness. Participants in this trial will receive the Durvalumab and Tremelimumab combination, specifically targeting those with a moderate to high tumor mutational burden. ^{2 6 7 8 9}

Who Is on the Research Team?

John Villano, MD, PhD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

Adults over 18 with relapsed/refractory solid tumors and a high or moderate tumor mutational burden, who haven't had prior anti-PD-1/PD-L1 or anti-CTLA-4 therapy. Participants must have good organ function, not be pregnant or breastfeeding, use effective contraception, and have no history of certain autoimmune diseases or uncontrolled illnesses.

Inclusion Criteria

I am older than 18 years.

I am not pregnant and am post-menopausal or have had a negative pregnancy test if pre-menopausal.

I am a man who will use approved birth control methods if I have sex, or I won't have sex.

Exclusion Criteria

I have nerve damage that affects my daily activities.

I have side effects from past treatments that won't worsen with durvalumab or tremelimumab.

You have received an organ transplant from someone else in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Durvalumab and Tremelimumab combination therapy for treatment of relapse/refractory solid tumors with moderate to high tumor mutational burden

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab and Tremelimumab Combination

Trial Overview The trial is testing the combination of Durvalumab and Tremelimumab to see if they improve progression-free survival in patients with solid tumors that show somatic hypermutation. It's for those whose cancer has returned after treatment.

How Is the Trial Designed?

Group I: Patients with moderate to high tumor mutational burden Experimental Treatment 1 Intervention

Patients with recurrent or refractory disease in solid tumors naïve to anti-PD-1/PD-L1 or anti-CTLA-4 immunotherapy and have moderate to high tumor mutational burden (TMB)

Who Is Running the Clinical Trial?

John L. Villano, MD, PhD

Lead Sponsor

Trials

3

Recruited

90+

Published Research Related to This Trial

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]

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]

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 single-dose regimen of 300 mg tremelimumab combined with durvalumab (STRIDE) shows a favorable benefit-risk profile for patients with unresectable hepatocellular carcinoma (uHCC), as demonstrated in phase I/II and phase III studies.

Higher exposure to tremelimumab is associated with longer overall survival in patients, with those having minimum serum drug concentrations above the median living significantly longer (18.99 months) compared to those below the median (10.97 months), although this relationship may be influenced by other patient characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-Response Analyses of Tremelimumab Monotherapy or in Combination with Durvalumab in Patients with Unresectable Hepatocellular Carcinoma. Song, X., Kelley, RK., Khan, AA., 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]

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 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]

In a phase 1b study involving 102 patients with advanced non-small cell lung cancer, the combination of durvalumab and tremelimumab demonstrated manageable safety, although 36% of patients experienced serious treatment-related adverse events, including three treatment-related deaths.

The treatment showed evidence of antitumor activity in both PD-L1-positive and PD-L1-negative tumors, with a confirmed objective response rate of 23% in the cohort receiving tremelimumab 1 mg/kg, indicating potential effectiveness regardless of PD-L1 status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. Antonia, S., Goldberg, SB., Balmanoukian, A., et al.[2022]

The combination of durvalumab and tremelimumab was studied in 19 articles involving 2052 patients with solid tumors, showing some benefits over traditional chemotherapy in certain tumor types.

However, this combination did not consistently outperform durvalumab alone, indicating that while it may have potential, further research with larger and better-designed studies is needed to clarify its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab Plus Tremelimumab in Solid Tumors: A Systematic Review. Arru, C., De Miglio, MR., Cossu, A., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8279985/

Durvalumab Plus Tremelimumab in Solid Tumors In study B, the median OS was 11.5 (95% CI 8.7–14.1) months with the combination durvalumab plus tremelimumab, and 8.7 (95% CI 6.5–11.7) months ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e20518

Durvalumab and tremelimumab combination therapy ... This meta-analysis demonstrates that durvalumab provides superior overall survival at 12 months compared to durvalumab + tremelimumab.

3. jto.org jto.org/article/S1556-0864(24)02264-0/fulltext

Durvalumab With or Without Tremelimumab in ... After a median follow-up of more than 5 years, T+D+CT had durable long-term OS benefit versus CT, supporting its use as first-line treatment in ...

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. sciencedirect.com sciencedirect.com/science/article/pii/S0169500223009601

Patient-reported outcomes with durvalumab, with or without ... First-line tremelimumab plus durvalumab and chemotherapy significantly improved overall survival and progression-free survival versus chemotherapy in ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37146752/

Brief Report: Safety and Antitumor Activity of Durvalumab ... Conclusions: Durvalumab plus tremelimumab had a manageable safety profile, but the combination did not have efficacy after PD-(L)1 treatment ...

7. 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%), ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2059702924014157

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. •. This combination did not improve ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT02938793

Study Details | NCT02938793 | Durvalumab in ... This is an investigator initiated single institution, open-label study to evaluate the antitumor activity, safety, and tolerability of durvalumab in combination ...