mRNA-2752 + Durvalumab for Advanced Cancers

Recruiting at 23 trial locations

Overseen By Moderna Clinical Trials Support Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: ModernaTX, Inc.

Must not be taking: Immunosuppressants, Anticoagulants, others

Disqualifiers: Active infection, Autoimmune disorders, others

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

Compensation: Varies

Number of Visits: Unknown

134 Participants Needed

Trial Summary

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 have used immunosuppressive medication within 14 days before starting the study treatment, and you must not require active systemic anticoagulation at the time of intratumoral injection or biopsy.

What data supports the effectiveness of the drug Durvalumab?

Research shows that Durvalumab, when used after chemoradiotherapy in patients with certain types of lung cancer, significantly improves survival rates and helps prevent the cancer from getting worse. It has been shown to be effective and safe in various studies, including the PACIFIC trial. ^{1 2 3 4 5}

Is the combination of mRNA-2752 and Durvalumab safe for humans?

Durvalumab has been studied in various trials and is generally considered safe, with common side effects including rash and thyroid issues. In some studies, serious immune-related side effects like pneumonitis occurred in a small percentage of patients. ^{1 3 6 7 8}

How is the drug mRNA-2752 + Durvalumab unique for treating advanced cancers?

The combination of mRNA-2752 and Durvalumab is unique because it involves using mRNA technology to potentially enhance the immune response against cancer cells, alongside Durvalumab, which is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. This approach is different from traditional treatments as it combines a novel mRNA-based component with an established immunotherapy. ^{1 2 9 10 11}

What is the purpose of this trial?

The clinical study will assess the safety and tolerability of escalating intratumoral doses of mRNA-2752 in participants with relapsed/refractory solid tumor malignancies or lymphoma.

Eligibility Criteria

This trial is for adults with advanced or metastatic solid tumors or lymphoma, weighing over 30 kg, who have progressed after standard treatments. They must be clinically stable, able to provide tumor biopsies, and not pregnant. Exclusions include recent radiotherapy, active bleeding disorders, immunosuppressive drug use within 14 days prior to treatment start, autoimmune/inflammatory disorders history, major surgery within the past month or minor procedures in the last week.

Inclusion Criteria

My thyroid function is normal, or I have stable hypothyroidism with proper treatment.

Written informed consent prior to completing any study-specific procedure

I weigh more than 30 kilograms.

Exclusion Criteria

I have not had radiotherapy or cancer treatment in the last 14 days.

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

I do not have any serious ongoing illnesses that would affect my participation in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of mRNA-2752 to determine the maximum tolerated dose or recommended dose for expansion

8-12 weeks

Dose Confirmation

Participants receive the identified dose to confirm its appropriateness for those with visceral lesions

4-8 weeks

Dose Expansion

Participants receive the recommended dose in Arm B to further evaluate safety and efficacy

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Durvalumab
• mRNA-2752

Trial Overview The study tests escalating doses of mRNA-2752 injected directly into tumors alongside Durvalumab in patients with relapsed/refractory cancers. It aims to determine safety and tolerability while observing any potential therapeutic effects on various types of cancerous growths.

Participant Groups

Group I: Arm C: mRNA-2752 Alone or mRNA-2752 + Durvalumab Experimental Treatment 2 Interventions

Participants will be administered mRNA-2752 at an applicable dose as monotherapy or in combination with durvalumab.

Group II: Arm B: mRNA-2752 + Durvalumab Experimental Treatment 2 Interventions

Participants will be administered mRNA-2752 at an applicable dose in combination with durvalumab.

Group III: Arm A: mRNA-2752 Experimental Treatment 1 Intervention

Participants will be administered mRNA-2752 at an applicable dose as monotherapy.

Who Is Running the Clinical Trial?

ModernaTX, Inc.

Lead Sponsor

Trials

127

Recruited

66,790,000+

Dr. Stephen Hoge

ModernaTX, Inc.

Chief Medical Officer

MD from Harvard Medical School

Stéphane Bancel

ModernaTX, Inc.

Chief Executive Officer since 2011

MBA from Harvard Business School, MSc in Engineering from École Centrale Paris

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

Findings from Research

In the phase II ATLANTIC study, durvalumab demonstrated encouraging overall survival (OS) rates in heavily pretreated patients with advanced non-small cell lung cancer (NSCLC), with median OS ranging from 9.3 to 13.3 months depending on tumor characteristics.

The safety profile of durvalumab remained consistent with previous reports, showing no new safety concerns, indicating it is a tolerable treatment option for patients with advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final overall survival and safety update for durvalumab in third- or later-line advanced NSCLC: The phase II ATLANTIC study. Garassino, MC., Cho, BC., Kim, JH., et al.[2021]

In the phase III PACIFIC trial, durvalumab significantly improved overall survival (OS) and progression-free survival (PFS) in patients with unresectable stage III non-small-cell lung cancer after chemoradiotherapy, with a 5-year OS rate of 42.9% compared to 33.4% for placebo.

The updated analyses, with a median follow-up of 34.2 months, showed that durvalumab continues to provide durable benefits, establishing a new standard of care for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. Spigel, DR., Faivre-Finn, C., Gray, JE., et al.[2022]

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 study of 421 patients with stage III nonsmall-cell lung cancer (NSCLC) who completed chemoradiation, 76.5% initiated adjuvant durvalumab, indicating a strong uptake of this treatment in real-world settings.

The initiation of adjuvant durvalumab increased significantly over time, from 66% to 92%, suggesting that it has been rapidly integrated into clinical practice, particularly among patients with better performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uptake of Adjuvant Durvalumab After Definitive Concurrent Chemoradiotherapy for Stage III Nonsmall-cell Lung Cancer. Bryant, AK., Yin, H., Schipper, MJ., et al.[2023]

In a study of 34 patients with locally advanced non-small cell lung cancer (LA-NSCLC) treated with chemoradiotherapy followed by durvalumab, 26.5% experienced symptomatic pneumonitis, but this did not negatively affect their overall survival or progression-free survival.

The management of pneumonitis included steroid treatment, and 70% of patients were able to safely resume durvalumab after recovery, indicating that re-challenging with durvalumab is feasible even after pneumonitis occurs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implications of pneumonitis after chemoradiation and durvalumab for locally advanced non-small cell lung cancer. Hassanzadeh, C., Sita, T., Savoor, R., et al.[2022]

In the phase III PACIFIC trial, durvalumab treatment led to a low incidence of immune-mediated adverse events (imAEs), with any-grade immune-mediated pneumonitis occurring in 9.4% of patients and grade 3/4 imAEs in only 3.4%.

Despite the occurrence of imAEs being more common with durvalumab compared to placebo, these events were generally manageable with treatments like corticosteroids, indicating that the benefits of the PACIFIC regimen outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing immune-mediated adverse events with durvalumab in patients with unresectable stage III NSCLC: A post-hoc analysis of the PACIFIC trial. Naidoo, J., Vansteenkiste, JF., Faivre-Finn, C., et al.[2022]

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Final overall survival and safety update for durvalumab in third- or later-line advanced NSCLC: The phase II ATLANTIC study. [2021]

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

Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. [2022]

3. United States 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. [2022]

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

Uptake of Adjuvant Durvalumab After Definitive Concurrent Chemoradiotherapy for Stage III Nonsmall-cell Lung Cancer. [2023]

5. China pubmed.ncbi.nlm.nih.gov

Implications of pneumonitis after chemoradiation and durvalumab for locally advanced non-small cell lung cancer. [2022]

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

Tolerability and efficacy of durvalumab in Japanese patients with advanced solid tumors. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Analysis of Durvalumab after Chemoradiation in Stage III Non-Small-Cell Lung Cancer. [2023]

8. Ireland pubmed.ncbi.nlm.nih.gov

Characterizing immune-mediated adverse events with durvalumab in patients with unresectable stage III NSCLC: A post-hoc analysis of the PACIFIC trial. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Outcomes with durvalumab by tumour PD-L1 expression in unresectable, stage III non-small-cell lung cancer in the PACIFIC trial. [2021]

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

Interferon Gamma Messenger RNA Signature in Tumor Biopsies Predicts Outcomes in Patients with Non-Small Cell Lung Carcinoma or Urothelial Cancer Treated with Durvalumab. [2022]