Immune Therapy for Germ Cell Cancer

Not currently recruiting at 8 trial locations

Overseen By Darren Feldman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, PD-1/PD-L1 inhibitors

Disqualifiers: Autoimmune disorders, Active infection, 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: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two immune therapies, durvalumab and tremelimumab, to determine their safety and effectiveness in treating germ cell tumors that have returned or are not responding to other treatments. Participants will receive these medications through an IV over several months. This trial may suit individuals diagnosed with germ cell cancer who have experienced tumor growth or recurrence after previous treatments. 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 to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have used immunosuppressive medication within 28 days before the first dose of the study drugs, except for certain types of steroids. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that durvalumab with tremelimumab is likely to be safe for humans?

Research has shown that the combination of durvalumab and tremelimumab is generally safe. Most participants tolerate these treatments without major issues. For instance, in some studies, only a few experienced serious side effects like lung inflammation, which could be treated and reversed.

These findings suggest that durvalumab and tremelimumab can be administered safely, though monitoring for side effects remains important. Prospective trial participants may find reassurance in these safety results. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of Durvalumab and Tremelimumab for treating germ cell cancer because this duo harnesses the power of the immune system to fight cancer cells. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, these immunotherapies specifically target immune checkpoints. Durvalumab and Tremelimumab work together to block proteins that usually keep the immune system from attacking cancer, potentially leading to a more precise and robust response against the tumor. This approach might offer a new hope for patients, especially those who have not responded well to standard treatments like cisplatin-based chemotherapy.

What evidence suggests that durvalumab with tremelimumab might be an effective treatment for germ cell cancer?

Research has shown that using durvalumab and tremelimumab together might help treat germ cell tumors that have returned or are difficult to treat. In one study, 13.8% of patients did not experience cancer progression over 16 weeks. Another study found that this treatment benefited 24.32% of patients whose tumors did not respond to standard platinum-based treatments. This trial will evaluate the combination of durvalumab and tremelimumab, which may not work for everyone but could help some patients by slowing or improving their cancer. Additionally, some improvement in overall survival rates suggests this combination could be a promising option for these challenging cases. ^{2 6 7 8 9}

Who Is on the Research Team?

Samuel Funt, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with relapsed/refractory germ cell tumors, weighing more than 30 kg, and having a performance status of 0-2. They must have measurable disease or elevated tumor markers and be willing to follow contraception guidelines if applicable. Excluded are those with recent major surgery, certain medical conditions like autoimmune disorders or lung issues, previous immune therapy treatments, uncontrolled illnesses, or infections like HIV.

Inclusion Criteria

I weigh more than 30 kilograms.

My cancer has worsened after at least one treatment.

My organs and bone marrow are functioning well.

Exclusion Criteria

I do not have active infections like TB, hepatitis B, hepatitis C, or HIV.

I am not pregnant or breastfeeding.

I have not had major surgery in the last 28 days.

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 by IV every 4 weeks for up to 4 doses, followed by durvalumab every 4 weeks for 9 doses

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab, Tremelimumab

Trial Overview The trial is testing the combination of two immune therapies: Durvalumab (MEDI4736) and Tremelimumab for patients whose germ cell tumors have returned or resisted treatment. It aims to determine how safe and effective this combination is in managing these types of tumors.

How Is the Trial Designed?

Group I: Duravalumab + Tremelimumab Experimental Treatment 2 Interventions

Duravalumab/Tremelimumab: Durvalumab and Tremelimumab will be administered by IV every 4 weeks for up to 4 doses/cycles, then Durvalumab by IV every 4 weeks starting at Week 16 for 9 doses (total treatment duration of 12 months). Participants enrolled now will receive tremelimumab \*300mg with durvalumab 1500mg for 1 cycle followed by 12 cycles of durvalumab 1500mg every 4 weeks or until lack of clinical benefit or unacceptable toxicity.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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

Published Research Related to This Trial

In a study of 113 patients with chemotherapy-refractory gastric or gastroesophageal junction cancer, the combination of durvalumab and tremelimumab showed low overall response rates, with the highest at 15.8% for the combination therapy in the third-line treatment group.

Despite the low efficacy, the study did not identify any new safety concerns, and it suggests that using a tumor-based IFNγ gene signature could be a promising approach to enhance treatment responses in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Durvalumab and Tremelimumab Alone or in Combination in Patients with Advanced Gastric and Gastroesophageal Junction Adenocarcinoma. Kelly, RJ., Lee, J., Bang, YJ., et al.[2021]

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 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]

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]

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 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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1567576924015637

Clinical outcome and prognostic factors for immunotherapy ... Immunotherapy achieved a 24.32 % response rate in platinum-refractory GCT patients. · Median progression-free survival was 4.67 months; overall ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.5040

A single-arm, phase II study of durvalumab (D) and ... Among 29 treated pts, the 16-wk PFS was 13.8% (range, 4.3-28.6), and median PFS and OS were 1.4 (95% CI: 4.1, 7.1) and 7.3 mo (95% CI: 3.2, 10.9) ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30243800/

An Open-label Randomized Phase 2 study of Durvalumab ... An open-label randomized Phase 2 study of durvalumab alone or in combination with tremelimumab in patients with advanced germ cell tumors (APACHE).

4. urotoday.com urotoday.com/conference-highlights/esmo-2019/esmo-2019-testicular-cancer/115405-esmo-2019-apache-an-open-label-randomized-phase-2-study-of-durvalumab-alone-or-in-combination-with-tremelimumab-in-patients-with-refractory-germ-cell-tumors-results-from-the-expanded-combination-therapy-cohort.html

APACHE: An Open Label, Randomized, Phase 2 Study of ... The median progression-free survival (PFS) with Durva monotherapy was 1.25 months and median overall survival (OS) was 3.36 months. No patients ...

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

Durvalumab Plus Tremelimumab in Solid Tumors It has an extremely poor prognosis, with a 5-year survival rate at approximately 7% [72, 73]. The only curative treatment is complete surgical ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.4547

An open label, randomized, phase 2 study of durvalumab ... One pt (5.6%) had reversible G3 irAE (pneumonitis) in arm B. In arm A, 100% of pts had disease progression (PD), all with features of ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7360234/

Durvalumab and tremelimumab combination therapy ... Conclusion: Durvalumab and tremelimumab combination therapy had a good safety profile and resulted in clinical benefit in head and neck ...

8. 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 ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT03081923?tab=table

Durvalumab Alone or With Tremelimumab in Refractory ... Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included after consultation ...