MDNA11 + Pembrolizumab for Cancer

(ABILITY-1 Trial)

Recruiting at 29 trial locations

Overseen By Nina Merchant

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Medicenna Therapeutics, Inc.

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Active CNS metastases, Autoimmune disease, Severe systemic disease, others

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

Compensation: Varies

Number of Visits: 8

Duration: 24 months

115 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had any systemic anti-cancer therapy within 4 weeks before starting the trial, and certain other treatments like corticosteroids or investigational drugs may also need to be stopped. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug MDNA11 + Pembrolizumab for cancer?

Pembrolizumab, a part of the treatment, has shown effectiveness in treating advanced melanoma and non-small-cell lung cancer (NSCLC), with studies indicating improved response rates and survival outcomes in these conditions. Additionally, PD-1 blockade, which is a mechanism of pembrolizumab, achieved responses in 70% of patients with desmoplastic melanoma. ^{1 2 3 4 5}

What is known about the safety of MDNA11 and Pembrolizumab for cancer treatment?

Pembrolizumab, a type of immune therapy, is generally well tolerated but can cause side effects like fatigue, rash, and diarrhea. It may also lead to less common immune-related issues such as thyroid problems, lung inflammation, and liver inflammation. There is no specific safety data available for MDNA11 in the provided research. ^{2 6 7 8 9}

What makes the drug MDNA11 + Pembrolizumab unique for cancer treatment?

MDNA11 is an IL-2 Superkine, which means it is a modified version of a protein that can boost the immune system's ability to fight cancer, and when combined with Pembrolizumab, an anti-PD-1 drug, it may enhance the immune response against cancer cells more effectively than using Pembrolizumab alone. ^{2 4 5 10 11}

What is the purpose of this trial?

This is a Phase 1/2, multi-center, open-label, dose-escalation and expansion study to evaluate safety and tolerability, PK, pharmacodynamic, and early signal of anti-tumor activity of MDNA11 alone or in combination with a checkpoint inhibitor in patients with advanced solid tumors.

Research Team

Arash Yavari, MBBS

Principal Investigator

Medicenna Therapeutics

Nina Merchant

Principal Investigator

Medicenna Therapeutics

Eligibility Criteria

Adults with advanced solid tumors that can't be surgically removed, who have measurable disease and a life expectancy of at least 12 weeks. They must function relatively well daily (ECOG 0-1), have good organ function, not be pregnant or breastfeeding, and agree to use effective birth control. Exclusions include recent other cancer treatments, active brain metastases, significant autoimmune diseases, certain infections like hepatitis B/C, or any condition that could affect safety or study results.

Inclusion Criteria

Agree to use highly effective contraception methods. WOCBP must agree to use highly effective birth control

My cancer is advanced or has spread and confirmed by lab tests.

Must be able and willing to provide written informed consent prior to start of any study procedures and assessments and must be willing to comply with all study procedures

Exclusion Criteria

I received my last cancer treatment within the required timeframe.

Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to start of treatment. Concomitant participation in an observational study must be discussed on a case-by-case basis with the MM for approval

I have brain metastases but they are stable after treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MDNA11 alone or in combination with pembrolizumab, with tumor assessments every 8 weeks

24 months

Every 8 weeks for tumor assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Checkpoint Inhibitor
• MDNA11

Trial Overview The trial is testing MDNA11 alone or combined with Pembrolizumab in patients with various advanced cancers. It's an early-phase study assessing the drugs' safety profiles, how they move through and affect the body (pharmacokinetics/dynamics), and their preliminary effectiveness against tumors.

Participant Groups

Group I: MDNA11 Experimental Treatment 2 Interventions

MDNA11 is a long-acting "beta-only" recombinant interleukin-2 (rIL-2) albumin fusion

Who Is Running the Clinical Trial?

Medicenna Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

160+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In a long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.

Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. Awad, MM., Gadgeel, SM., Borghaei, H., et al.[2021]

In a phase 1b study involving 28 patients with myelodysplastic syndromes (MDS) resistant to hypomethylating agents, pembrolizumab demonstrated manageable safety, with 36% experiencing treatment-related adverse events, but no patients achieved a complete or partial response.

Despite the lack of significant tumor response, 19% of patients showed a complete response in bone marrow, and the median overall survival was 6 months, indicating some clinical activity in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for myelodysplastic syndromes after failure of hypomethylating agents in the phase 1b KEYNOTE-013 study. Garcia-Manero, G., Ribrag, V., Zhang, Y., et al.[2022]

In a retrospective analysis, PD-1 blockade treatment showed a remarkable response rate of 70% in patients with desmoplastic melanoma, indicating its potential efficacy for this specific cancer type.

This finding suggests that PD-1 blockade could be a promising therapeutic option for patients suffering from desmoplastic melanoma, although further studies are needed to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients with Desmoplastic Melanoma May Respond to PD-1 Blockade. [2019]

In a phase 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC) expressing PD-L1, pembrolizumab significantly improved median progression-free survival to 10.3 months compared to 6.0 months with chemotherapy, indicating its efficacy as a treatment option.

Patients receiving pembrolizumab also experienced fewer treatment-related adverse events (73.4% vs. 90.0% for chemotherapy), highlighting its safety profile alongside its effectiveness in prolonging survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. Abdel-Rahman, O.[2018]

The combination of ex vivo activated natural killer (NK) cell therapy (SNK01) with pembrolizumab was found to be safe, with no new safety concerns and a maximum tolerated dose established at 4×10^9 cells per infusion.

Patients receiving the NK cell combination therapy showed a significantly higher objective response rate (41.7% vs. 0%) and longer median progression-free survival (6.2 months vs. 1.6 months) compared to those receiving pembrolizumab alone, indicating enhanced efficacy in treating advanced non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I/IIa Randomized Trial Evaluating the Safety and Efficacy of SNK01 Plus Pembrolizumab in Patients with Stage IV Non-Small Cell Lung Cancer. Kim, EJ., Cho, YH., Kim, DH., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor known for its antitumor effects, can cause multiple inflammatory adverse events, highlighting the need for awareness of its side effects.

This case emphasizes the importance of early identification of various cutaneous side effects associated with immunotherapy, which can affect patient management and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-induced sarcoid granulomatous panniculitis and bullous pemphigoid in a single patient. Honigman, AD., Lai, F., Elakis, J., et al.[2021]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

An elderly male patient on pembrolizumab developed four autoimmune toxicities, including type 1 diabetes and pneumonitis, highlighting the risk of multiple immune-related adverse events associated with this treatment.

The case suggests that aging may increase susceptibility to these adverse effects, necessitating close monitoring and prompt management, including stopping the immunotherapy and using steroids for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple autoimmune side effects of immune checkpoint inhibitors in a patient with metastatic melanoma receiving pembrolizumab. Kethireddy, N., Thomas, S., Bindal, P., et al.[2021]

Pembrolizumab, a monoclonal antibody that blocks PD-1, effectively enhances antitumor immune responses and has been approved for treating advanced melanoma, renal cell cancer, and non-small cell lung cancer.

In vivo studies using PET imaging showed that pembrolizumab is stable in circulation and primarily accumulates in the liver and spleen, providing valuable insights into its pharmacokinetics and potential for optimizing dosing strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Pharmacokinetics and Biodistribution Studies of 89Zr-Labeled Pembrolizumab. England, CG., Ehlerding, EB., Hernandez, R., et al.[2020]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

References

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

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. [2021]

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

Pembrolizumab for myelodysplastic syndromes after failure of hypomethylating agents in the phase 1b KEYNOTE-013 study. [2022]

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

Patients with Desmoplastic Melanoma May Respond to PD-1 Blockade. [2019]

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

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. [2022]

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

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. [2018]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

A Phase I/IIa Randomized Trial Evaluating the Safety and Efficacy of SNK01 Plus Pembrolizumab in Patients with Stage IV Non-Small Cell Lung Cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab-induced sarcoid granulomatous panniculitis and bullous pemphigoid in a single patient. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. [2020]

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

Multiple autoimmune side effects of immune checkpoint inhibitors in a patient with metastatic melanoma receiving pembrolizumab. [2021]

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

Preclinical Pharmacokinetics and Biodistribution Studies of 89Zr-Labeled Pembrolizumab. [2020]

11. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]