mRNA-2752 + Durvalumab for Advanced Cancers

No longer recruiting at 24 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of a new treatment called mRNA-2752, used alone or with durvalumab (an immunotherapy), for people with advanced cancers. The trial aims to determine the right dose and assess how the treatments work for those whose cancer has returned or worsened despite other treatments. Candidates may qualify if they have experienced cancer progression after standard treatments like chemotherapy or immune therapy and have a tumor that can be safely biopsied. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in 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 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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that mRNA-2752 is generally safe and well-tolerated. One study found that this treatment, both alone and combined with durvalumab, was safe for patients with difficult-to-treat tumors like melanoma. Patients did not experience severe side effects, indicating good tolerability.

Durvalumab, a drug often used in cancer treatment, has been part of successful treatments before. In other studies, many patients treated with durvalumab remained alive after three years, indicating its safety and effectiveness.

Overall, both treatments have shown promising safety results from earlier research. While this is still an early-phase trial, these findings offer reassurance about the safety of mRNA-2752 and its combination with durvalumab. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about mRNA-2752 and its combination with durvalumab because they represent a novel approach to treating advanced cancers. Unlike traditional chemotherapy, which indiscriminately targets rapidly dividing cells, mRNA-2752 uses messenger RNA technology to instruct the body’s own cells to produce proteins that can stimulate an immune response against cancer cells. Durvalumab, on the other hand, is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. This combination aims to not just attack cancer directly but also enhance the body's natural defenses, potentially leading to more targeted and sustained cancer suppression. This innovative mechanism of action is what sets these treatments apart from current options and fuels the excitement in the research community.

What evidence suggests that this trial's treatments could be effective for advanced cancers?

Research has shown that mRNA-2752 may help treat certain cancers by boosting the immune system to attack and destroy cancer cells. In this trial, participants will receive mRNA-2752 either as monotherapy or in combination with another drug, durvalumab. Early studies have shown positive results for mRNA-2752, both alone and with durvalumab, in hard-to-treat cancers like melanoma and triple-negative breast cancer. Durvalumab has also lowered the risk of death in some cancer patients. These findings suggest that mRNA-2752, especially when combined with durvalumab, could effectively treat advanced cancers. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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]

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 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]

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]

Citations

1. jitc.bmj.com jitc.bmj.com/content/10/suppl_2/a798

767 Safety and preliminary efficacy of mRNA-2752, a lipid ... ITu mRNA-2752 + IV durvalumab is safe, tolerable, and shows preliminary efficacy in immune refractory tumors, including TNBC and melanoma.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03739931

NCT03739931 | Dose Escalation Study of mRNA-2752 for ... The clinical study will assess the safety and tolerability of escalating intratumoral doses of mRNA-2752 in participants with relapsed/refractory solid tumor ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10511650/

Recent advances in mRNA cancer vaccines mRNA cancer vaccines have emerged as a promising novel approach to cancer immunotherapy, offering high specificity, better efficacy, and fewer side effects.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.3092

A phase I study of mRNA-2752, a lipid nanoparticle ... Results: As of 20 December 2019, 23 solid tumor patients have been treated either with mRNA-2752 alone (n = 14) or in combination (n = 9) and ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0169409X23003083

mRNA: A promising platform for cancer immunotherapy Along with the promising results of mRNA vaccines against infectious diseases, research on mRNA vaccines for cancer treatment is gaining immense attention.

6. mayo.edu mayo.edu/research/clinical-trials/cls-20545137

Dose Escalation Study of mRNA-2752 for Intratumoral ... The purpose of this study is to assess the safety and tolerability of escalating intratumoral doses of mRNA-2752 in participants with relapsed/ ...