MDNA11 + Pembrolizumab for Cancer

(ABILITY-1 Trial)

Recruiting at 37 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, MDNA11, to determine its safety and effectiveness for people with advanced solid tumors (tumors that have spread and are not confined to a specific organ). MDNA11, also known as IL-2 Superkine, may be used alone or with pembrolizumab (a checkpoint inhibitor) to enhance the immune system's ability to fight cancer. The trial aims to assess the effectiveness of these treatments and identify any side effects. Individuals with a confirmed advanced solid tumor who meet certain health criteria might qualify for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that MDNA11 and checkpoint inhibitors are likely to be safe for humans?

Research has shown that MDNA11, a new treatment for advanced solid tumors, is safe for patients. In studies, patients tolerated MDNA11 well, and no severe side effects were linked to the doses given. MDNA11 activates certain immune cells, helping the body fight cancer without major safety concerns. This is encouraging for those considering participation in a trial with MDNA11. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

MDNA11 is unique because it is a long-acting recombinant interleukin-2 (rIL-2) albumin fusion, specifically designed to target cancer cells more effectively while minimizing damage to healthy cells. Unlike standard cancer treatments like chemotherapy, which can affect both healthy and cancerous cells, MDNA11 focuses on enhancing the immune system's ability to fight cancer by promoting the activity of certain immune cells. This selective activation is achieved through its "beta-only" mechanism, potentially leading to fewer side effects and improved patient outcomes. Researchers are excited about MDNA11 because it represents a novel approach to cancer treatment, aiming to boost the body's natural defenses with precision and durability.

What evidence suggests that MDNA11 might be an effective treatment for cancer?

Research has shown that MDNA11, a new treatment, is promising in early studies for treating advanced solid tumors. In previous studies, MDNA11, either alone or with pembrolizumab (a type of cancer drug), led to noticeable tumor shrinkage in 10 patients, with 5 cases confirmed. In this trial, participants will receive MDNA11 alone. When used by itself, MDNA11 helped shrink tumors or stop them from growing in about 19.2% of patients, with a response rate of 7.7%. Lab tests demonstrated that MDNA11 has strong and lasting effects against cancer. Overall, these findings suggest MDNA11 could be an effective treatment option for some patients with advanced cancers. ^{3 4 6 7 8}

Who Is on the Research Team?

Nina Merchant

Principal Investigator

Medicenna Therapeutics

Arash Yavari, MBBS

Principal Investigator

Medicenna Therapeutics

Are You a Good Fit for This Trial?

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

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

Life expectancy of ≥ 12 weeks

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

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]

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]

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 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]

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, 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]

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]

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]

Citations

1. ir.medicenna.com ir.medicenna.com/news-releases/news-release-details/medicenna-presents-compelling-results-ability-1-clinical-trial

Medicenna Presents Compelling Results from the ABILITY-1 ... Ten (10) patients have achieved an objective response (5 confirmed) when treated with MDNA11 alone or in combination with KEYTRUDA® (pembrolizumab).

2. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A785

684 Results from ABILITY-1 monotherapy dose escalation ... MDNA11 demonstrated a favorable safety profile and compelling single-agent activity in dose escalation and ongoing dose expansion in heavily pretreated ...

3. aacrjournals.org aacrjournals.org/cancerres/article/84/7_Supplement/CT259/742282/Abstract-CT259-Results-from-monotherapy-dose

Results from monotherapy dose escalation of MDNA11, a long ... With study currently ongoing, single agent clinical activity was evident with an ORR of 7.7% and Clinical Benefit Rate (CBR) of 19.2% (2 PRs + 3 ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT345871

MDNA11 is a long-acting IL-2 superkine that potentiates ... In CT26 and MC38 syngeneic tumor models, MDNA11 demonstrates potent and durable efficacy as monotherapy following a Q1W dose schedule for 2 weeks. Synergy with ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8772458/

Fine-tuned long-acting interleukin-2 superkine potentiates ... MDNA11 is a next generation long-acting IL-2 immunotherapeutic with a highly favorable pharmacodynamic profile that translates to a strong therapeutic efficacy.

6. ir.medicenna.com ir.medicenna.com/news-releases/news-release-details/updated-mdna11-monotherapy-and-combination-clinical-data-ongoing

Updated MDNA11 Monotherapy and Combination Clinical ... The oral presentation will include updated clinical data from the monotherapy and combination arms of the ongoing Phase 1/2 ABILITY-1 Study ...

7. onclive.com onclive.com/view/mdna11-generates-activity-safety-in-advanced-solid-tumors

MDNA11 Generates Activity, Safety in Advanced Solid ... Treatment with the long-acting interleukin-2 superkine led to durable tumor control and no dose-limiting toxicities in patients with advanced solid tumors.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05086692

NCT05086692 | A Beta-only IL-2 ImmunoTherapY Study MDNA11 specifically engineered to overcome the shortcomings of rhIL-2 (aldesleukin) by preferentially activating immune effector cells (CD8+ T- and NK cells) ...