MEDI5752 for Solid Cancers

Not currently recruiting at 41 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: MedImmune LLC

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Autoimmune disorders, Organ transplant, 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 tests the safety and effectiveness of a new treatment called MEDI5752 (a PD-1/CTLA-4 bispecific monoclonal antibody) for individuals with advanced solid tumors. The study examines MEDI5752 both alone and in combination with common chemotherapy drugs such as carboplatin, pemetrexed, paclitaxel, or nab-paclitaxel. It seeks to determine the effectiveness of these treatments and whether they offer a better option for those with hard-to-treat cancers. Individuals diagnosed with advanced solid tumors who have undergone previous cancer treatments may be suitable candidates for this trial. As a Phase 1 trial, this research focuses on understanding the treatment's effects in participants, providing them the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but there is a washout period (time without taking certain medications) for those who have had prior cancer treatments like anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapies. It's best to discuss your specific medications with the trial team.

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

An earlier study showed that MEDI5752 had promising safety results in humans. Patients tolerated doses ranging from 2.25 to 2500 mg well. There were also encouraging signs of its potential effectiveness against advanced solid tumors. Although still under investigation, this suggests it could be safe to use.

Early data indicates that MEDI5752 remains safe when combined with chemotherapy. The combination did not lead to a high rate of severe side effects, suggesting that adding it to chemotherapy might be tolerable for patients.

While these results are promising, it is important to remember that this research is ongoing. As it is in an early phase of trials, more studies are needed to confirm long-term safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about MEDI5752 because it targets both PD-1 and CTLA-4 pathways, which are crucial immune checkpoints in cancer treatment, offering a potentially more effective approach than current single-pathway therapies. Unlike standard treatments that typically target only one immune pathway, MEDI5752 aims to enhance the immune system's ability to fight off cancer cells more robustly. In combination with chemotherapy, as in one of the trial's arms, this dual-targeting mechanism may lead to improved outcomes for patients with solid cancers. Additionally, the combination of MEDI5752 with standard chemotherapy drugs like pemetrexed and carboplatin could provide a synergistic effect, potentially leading to better survival rates and response for patients compared to existing treatments.

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

Research has shown that MEDI5752 holds promise for treating advanced cancers. This special antibody targets two proteins that aid cancer growth. The trial includes an arm where participants receive MEDI5752 alone, which demonstrated strong and lasting effects against tumors, particularly in patients with advanced kidney cancer. Another arm will test MEDI5752 combined with chemotherapy drugs like carboplatin and paclitaxel, potentially enhancing its cancer-fighting effects. Although early results are positive, further research is needed to fully understand its effectiveness across different cancer types. ^{1 2 3 4 6}

Who Is on the Research Team?

Deepa Subramaniam, MD, MSc

Principal Investigator

AstraZeneca

Are You a Good Fit for This Trial?

Adults with advanced solid tumors who have a life expectancy of at least 12 weeks, can provide tumor material, and have adequate organ function. They must not be involved in the study's conduct or enrolled in another clinical trial. Participants need to use effective contraception and cannot have untreated brain metastases, uncontrolled illnesses, or a history of severe autoimmune disorders.

Inclusion Criteria

Life expectancy ≥ 12 weeks

Written informed consent and any locally required authorization

Subjects must provide tumor material as applicable

Exclusion Criteria

Involvement in the planning and/or conduct of the study (applies to both MedImmune staff and/or staff at the study site)

Concurrent enrollment in another clinical study, unless it is an observational clinical study or the follow-up period of an interventional study

Known allergy or reaction to any component of the planned study treatment

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 MEDI5752 to evaluate safety and tolerability

Up to 21 days

Multiple visits for dose administration and monitoring

Dose-expansion

Participants receive MEDI5752 and chemotherapy to further evaluate safety and antitumor activity

4 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 114 days following end of treatment

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• MEDI5752
• Nab-Paclitaxel
• Paclitaxel
• Pemetrexed

Trial Overview The trial is testing MEDI5752 alone or combined with chemotherapy drugs like carboplatin and pemetrexed or paclitaxel/nab-paclitaxel. It aims to see how well these treatments work for adults with various types of advanced solid tumors.

How Is the Trial Designed?

Group I: Arm B: MEDI5752 and chemotherapy Experimental Treatment 4 Interventions

MEDI5752, pemetrexed, carboplatin and paclitaxel.

Group II: Arm A: MEDI5752 Experimental Treatment 1 Intervention

MEDI5752

Group III: Arm C: Pembrolizumab and chemotherapy Active Control 3 Interventions

pembrolizumab, pemetrexed, and carboplatin

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

MedImmune LLC

Lead 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 II trial involving 45 patients with advanced gastric cancer, the combination of nab-paclitaxel and ramucirumab achieved an overall response rate of 54.8%, indicating significant efficacy as a second-line treatment.

The treatment was associated with manageable side effects, primarily decreased neutrophil and white blood cell counts, but no treatment-related deaths occurred, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of nab-paclitaxel in combination with ramucirumab in patients with previously treated advanced gastric cancer. Bando, H., Shimodaira, H., Fujitani, K., et al.[2023]

The maximum tolerated doses (MTD) of ABI-007 in combination with carboplatin were determined to be 300 mg/m², 100 mg/m², and 125 mg/m² for three different treatment schedules, indicating a well-defined dosing strategy for future studies.

The combination therapy was well tolerated with a lower incidence of severe neutropenia compared to traditional solvent-based paclitaxel, showing promising activity against various solid tumors, including lung and breast cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors. Stinchcombe, TE., Socinski, MA., Walko, CM., et al.[2018]

ABI-007, a novel formulation of paclitaxel, can be safely administered at higher doses than traditional paclitaxel formulations, with maximum-tolerated doses of 100 mg/m² for heavily pretreated patients and 150 mg/m² for lightly pretreated patients.

The study showed partial antitumor responses in patients with breast, lung, and ovarian cancers, indicating that ABI-007 may be effective even in those previously treated with standard paclitaxel formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignancies. Nyman, DW., Campbell, KJ., Hersh, E., et al.[2022]

In a Phase 2 study involving 29 patients with advanced non-small cell lung cancer (NSCLC) who had previously failed PD-(L)1 inhibitor treatment, nab-paclitaxel demonstrated a promising objective response rate (ORR) of 55.2%, indicating its efficacy as a subsequent treatment option.

The treatment was associated with manageable safety profiles, with significant toxicities including leukopenia (27.6%) and neutropenia (31.0%), suggesting that while nab-paclitaxel is effective, monitoring for these side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nanoparticle albumin-bound paclitaxel monotherapy after immune checkpoint inhibitor administration for advanced non-small cell lung cancer: A multicenter Phase 2 clinical trial. Sonoda, T., Umeda, Y., Demura, Y., et al.[2023]

In a study of 40 patients with stage III/IV squamous non-small-cell lung cancer, the combination of nab-paclitaxel and a platinum agent (cisplatin or carboplatin) resulted in a high overall response rate of 62.5% and a disease control rate of 92.5%, indicating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with most adverse effects being mild to moderate (grade 1 to 2), including myelosuppression and gastrointestinal issues, suggesting that nab-paclitaxel combined with platinum agents is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical investigation of efficacy of albumin bound paclitaxel plus platinum compounds as first-line chemotherapy for stage III/IV squamous non-small cell lung cancer. Fang, Y., Wang, L., Xia, GH., et al.[2022]

ABI-007, a novel nanoparticle formulation of paclitaxel, demonstrated a significant overall response rate of 48% in treating metastatic breast cancer, with even higher rates of 64% for first-line therapy, indicating its efficacy in this patient population.

The treatment was well-tolerated, with no severe hypersensitivity reactions reported despite the absence of premedication, and typical toxicities associated with paclitaxel, such as neutropenia and sensory neuropathy, were observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of ABI-007, an albumin-bound paclitaxel, in women with metastatic breast cancer. Ibrahim, NK., Samuels, B., Page, R., et al.[2022]

The combination of pemetrexed and nab-paclitaxel was found to be feasible and well tolerated in patients with advanced non-small cell lung cancer (NSCLC), with a recommended phase II dose established at pemetrexed 500 mg/m² and nab-paclitaxel 260 mg/m².

In a phase II trial involving 37 patients, the treatment showed a response rate of 14% and a disease control rate of 46%, with a median overall survival of 8.8 months, indicating some efficacy in second and third-line therapy despite the early closure of the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II trial of pemetrexed plus nab-paclitaxel in advanced solid tumor patients with emphasis on non-small cell lung cancer. Ho, C., Davies, AM., Sangha, RS., et al.[2023]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)01950-6/fulltext

1883MO MEDI5752 (volrustomig), a novel PD-1/CTLA-4 ... Volrustomig is a novel bispecific antibody with high degree of efficacy in 1L aRCC and across IMDC risk groups, with a low rate of upfront treatment failure.

2. aacrjournals.org aacrjournals.org/cancerres/article/82/12_Supplement/CT016/701946/Abstract-CT016-MEDI5752-a-novel-PD-1-CTLA-4

Abstract CT016: MEDI5752, a novel PD-1/CTLA-4 bispecific ... Here we present dose-escalation data from a phase I, open-label, multicenter study in advanced solid tumors (NCT03530397). Methods: Eligible ...

3. ejgo.org ejgo.org/pdf/10.3802/jgo.2024.35.e82

Bispecific immunotherapy MEDI5752 or volrustomig and ... MEDI5752 is a monovalent bispecific immunotherapy and is strategically unique as it combines both anti programmed cell death 1 and anti ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.107

Safety and clinical activity of MEDI5752, a PD-1/CTLA-4 ... MEDI5752 monotherapy showed deep and durable antitumor activity in pts with advanced RCC, despite high rates of treatment D/C, particularly in the 1L setting.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11262897/

Bispecific immunotherapy MEDI5752 or volrustomig and ... A phase I, open-label study (MedImmune LLC, NCT03530397) of MEDI5752 monotherapy 2.25–2,500 mg intravenous every 3 weeks showed encouraging antitumor activity ...

6. asco.org asco.org/abstracts-presentations/ABSTRACT363870

Safety and clinical activity of MEDI5752, a PD-1/CTLA-4 ... A phase I, open-label study (NCT03530397) of MEDI5752 monotherapy 2.25–2500 mg IV Q3W showed encouraging antitumor activity in advanced solid tumors. Maximum ...