MEDI5752 for Solid Cancers

Recruiting at 31 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

401 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called MEDI5752 along with common chemotherapy drugs in adults with advanced cancer. The goal is to see if MEDI5752 can help fight cancer on its own or when combined with chemotherapy.

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.

What data supports the effectiveness of the drug MEDI5752 for solid cancers?

Research shows that the combination of albumin-bound paclitaxel (a form of chemotherapy) and carboplatin has significant activity in treating various solid tumors, including lung and ovarian cancers. This suggests that similar combinations, like those in the trial, may also be effective for solid cancers. ^{1 2 3 4 5}

What safety data exists for MEDI5752 and related treatments in humans?

The safety data for albumin-bound paclitaxel (Abraxane) shows it has a different and generally safer side effect profile compared to solvent-based paclitaxel, with a lower rate of severe neutropenia (a condition where there are fewer white blood cells, which can increase infection risk). The combination of albumin-bound paclitaxel and carboplatin has been studied in various cancers, showing activity and manageable safety profiles. ^{1 2 3 4 6}

What makes the drug MEDI5752 for solid cancers unique?

The drug MEDI5752 is unique because it combines a bispecific antibody targeting both PD-1 and CTLA-4, which are proteins that help cancer cells evade the immune system, with other chemotherapy agents like carboplatin and nab-paclitaxel. This combination aims to enhance the immune response against cancer cells while reducing the side effects typically associated with solvent-based chemotherapy. ^{1 3 4 7 8}

Research Team

Deepa Subramaniam, MD, MSc

Principal Investigator

AstraZeneca

Eligibility Criteria

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

I am 18 years old or older.

Exclusion Criteria

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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]

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]

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]

References

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

A phase II trial of nab-paclitaxel (ABI-007) and carboplatin in patients with unresectable stage IV melanoma : a North Central Cancer Treatment Group Study, N057E(1). [2021]

2. United States 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. [2023]

3. Germany 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. [2018]

4. Thailand 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. [2022]

5. England pubmed.ncbi.nlm.nih.gov

A phase II study of nab-paclitaxel in combination with ramucirumab in patients with previously treated advanced gastric cancer. [2023]

6. United States 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. [2023]

7. United States 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. [2022]

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

Multicenter phase II trial of ABI-007, an albumin-bound paclitaxel, in women with metastatic breast cancer. [2022]