Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Digestive System Diseases

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Symptoms and General Pathology

Infections

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Squamous Cell

Adenocarcinoma

Stomach Neoplasms

Breast Neoplasms

Triple Negative Breast Neoplasms

Esophageal Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Urinary Bladder Neoplasms

Uterine Cervical Neoplasms

Melanoma

Carcinoma, Renal Cell

Microsatellite Instability

Squamous Cell Carcinoma of Head and Neck

Carcinoma, Basal Cell

Mesothelioma

Mesothelioma, Malignant

Skin Neoplasms

Melanoma, Cutaneous Malignant

Carcinoma, Merkel Cell

Fallopian Tube Neoplasms

Endometrial Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neoplasms, Squamous Cell

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Uterine Neoplasms

Uterine Diseases

Urologic Neoplasms

Urologic Diseases

Male Urogenital Diseases

Kidney Neoplasms

Kidney Diseases

Head and Neck Neoplasms

Breast Diseases

Adenoma

Neoplasms, Mesothelial

Fallopian Tube Diseases

Neoplasms, Basal Cell

Communicable Diseases

Polyomavirus Infections

Virus Diseases

DNA Virus Infections

Tumor Virus Infections

Carcinoma, Neuroendocrine

Stomach Cancer

Esophageal Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Fallopian Tube Cancer

Malignant Mesothelioma

Merkel Cell Carcinoma

Acral Lentiginous Melanoma

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Analgesics

Immune Checkpoint Inhibitors

Pembrolizumab

Immunomodulating Agents

Interleukin-2

Antineoplastic Agents, Immunological

Analgesics, Non-Narcotic

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

MDNA11 will be administered, IV on a once every 2 weeks (Q2W) dosing schedule. Provisional dose cohorts for monotherapy dose escalation doses ranging from 0.003 to 0.6 (mg/kg): until determining the monotherapy Recommended Dose for Expansion (mRDE).

MDNA11

MDNA11 will be administered in combination with pembrolizumab, IV. MDNA11 dose range to be evaluated in combination with pembrolizumab until determining the combination Recommended Dose for Expansion (cRDE).

Nina Merchant

Melissa Coello

Martin Bexon, MBBS

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.

The study drug, MDNA11, long-acting "beta-only" recombinant interleukin-2 (rIL-2). MDNA11 specifically engineered to overcome the shortcomings of rhIL-2 (aldesleukin) by preferentially activating immune effector cells (CD8+ T- and NK cells) responsible for killing cancer cells, with minimal or no stimulation of immunosuppressive Tregs. It is designed to potentially enhance host immune response and fusion to albumin increases the half-life further avoiding frequent dosing required with rhIL-2.

The study will be conducted at up to 30 clinical sites following regulatory authority and institutional review board / independent ethics committee (IRB/ IEC) approval and completion of informed consent. The study will be conducted in multiple parts:

* Monotherapy (MDNA11 alone) dose escalation
* Monotherapy (MDNA11 alone) dose expansion in select tumor types
* Combination (MDNA11 + pembrolizumab) dose escalation
* Combination (MDNA11 + pembrolizumab) dose expansion in select tumor types

Approximately 115 patients will be enrolled.

After commencing treatment (first exposure of MDNA11 alone or MDNA11 + pembrolizumab), tumor assessment by CT/MRI will be performed every 8 weeks ± 1 week until immune confirmed progressive disease ("iCPD") by iRECIST, discontinuation of study drug(s), withdrawal of consent or loss to follow-up. Treatment beyond progression may be permitted if criteria are met. Patients can withdraw from participation at any time.

Sequential dose escalation (MDNA11 monotherapy and MDNA11 + pembrolizumab) followed by dose expansion with MDNA11 monotherapy and combination (MDNA11 + pembrolizumab).

Male Female (Women of Childbearing Potential will be subject to pregnancy testing)

A Beta-only IL-2 ImmunoTherapY Study

A Phase 1/2 Open Label, Dose Escalation and Expansion Study of MDNA11, IL-2 Superkine, Administered Alone or in Combination With Immune Checkpoint Inhibitor in Patients With Advanced Solid Tumors

Measured by change in Tumor Infiltrating Lymphocyte (TIL) levels

Evaluation of tolerability as measured by number of patients with dose limiting toxicities (DLTs)

Rate of TRAEs in patients with advanced solid tumors

Rate of TEAEs in patients with advanced solid tumors

Maximum observed serum drug concentration

Time to maximum observed serum drug concentration

Area under the serum concentration vs time curve from time zero to the last measurable concentration

Incidence and persistence of anti-drug antibodies to MDNA11

Measurement of translational parameters - Flow cytometry analysis of immune cells in blood and serum measurements of cytokine levels

Assessed by RECIST v1.1 and iRECIST; CR+PR/Evaluable N

Time from signing ICF to disease progression

Merck Sharp & Dohme LLC

Medicenna Therapeutics, Inc.

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Avelumab

The mismatch repair deficient or microsatellite instable, or POLE mutated metastatic colorectal cancer patients who were progressed after at least one prior systemic treatment for metastatic setting.

After checking the eligibility for the study entry, patients will be entered into the study treatment with avelumab monotherapy.

Patients will receive 10 mg/kg of avelumab via intravenous infusion every 2 weeks.

Response evaluation will be performed every 6 weeks (± 1-week window period). Treatment will be continued until disease progression, unacceptable adverse events or the patient's refusal.

Treatment through progression is at the investigator's discretion, and the investigator should ensure that patients do not have any significant, unacceptable, or irreversible toxicity that indicate that continuing treatment will not further benefit the patient. The Investigator should ensure that patients still meet all of the inclusion criteria and none of the exclusion criteria for this study.

Tae Won Kim, Professor

The POLE mutations represent high somatic mutation loads in patients with colorectal cancer, especially in those with MMR proficient or MSS, therefore, tumors harbouring POLE mutations might be susceptible to immune checkpoint blockade.

Based on these reasons, Investigator planned a phase II study of avelumab monotherapy in patients with previously treated, metastatic, MMR deficient (MSI-H) or POLE mutated colorectal cancer.

Later-line therapies after failure of standard treatments for metastatic colorectal cancer patients are limited; regorafenib and TAS-102 have shown clinical activity for these patients, however, efficacy outcomes seemed not to be sufficient although there have been rather higher frequencies of adverse events.

Mismatch repair (MMR) deficiency or microsatellite instability-high (MSI-H) played a role of negative predictive factor for adjuvant fluorouracil-based chemotherapy in patients with resected colorectal cancer. In the metastatic setting, deficient MMR or MSI-H represented poor prognosis; however, their predictive role has been documented after the pembrolizumab trial was reported. The results of the pembrolizumab trial demonstrated that the PD-1 blockade with pembrolizumab monotherapy showed 40% of confirmed immune-related objective response rates in patients with MMR deficient metastatic colorectal cancers; hence there was no objective response in those with MMR proficient tumors. The progression-free rates at 20 weeks were 78% versus 11%, respectively, also favouring those with MMR deficient tumors. However, the MMR deficiency of MSI-H is found in only about 5% in patients with metastatic colorectal cancer, which is too small to expand potential candidate of immunotherapy.

One of the proposed mechanism of promising efficacy from pembrolizumab for MMR deficient colorectal cancer is that MMR deficient or MSI-H colorectal cancers harbour higher somatic mutation loads than MMR proficient colorectal cancer (a mean of 1782 somatic mutations per tumor in the MMR deficient tumors versus 73 in the MMR proficient tumors in the results of pembrolizumab trial); somatic mutations have the potential to encode non-self immunogenic antigens; therefore, immunotherapy enhancing immune surveillance produced promising treatment efficacy in the MMR deficient tumors.

The POLE gene encodes the catalytic subunit of DNA polymerase epsilon, and it involves DNA repair and chromosomal replication. The POLE mutations are located in the exonuclease domain, and their presence has already been reported in the various cancers including colorectal and endometrial cancer.

The POLE mutations represent high somatic mutation loads in patients with colorectal cancer, especially in those with MMR proficient or MSS, therefore, tumors harbouring POLE mutations might be susceptible to immune checkpoint blockade.

Based on these reasons, Investigator planned a phase II study of avelumab monotherapy in patients with previously treated, metastatic, MMR deficient (MSI-H) or POLE mutated colorectal cancer.

Avelumab for MSI-H or POLE Mutated Metastatic Colorectal Cancer

A Phase II Study of Avelumab in Patients With Mismatch Repair Deficient or POLE Mutated Metastatic Colorectal Cancer

Merck KGaA, Darmstadt, Germany

Asan Medical Center

Professor

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Beta-only IL-2 ImmunoTherapY Study	NCT05086692	Advanced Solid ... Unresectable So... Clear Cell Rena... Triple Negative... Non-Small Cell ... Non-Small Cell ... Colorectal Canc... Gastric Cancer Cervical Cancer Basal Cell Carc... Bladder Cancer Merkel Cell Car... Squamous Cell C... Cutaneous Squam... Pleural Mesothe... Esophageal Canc... Endometrial Car... Solid Tumor Solid Tumor, Ad... MSI-H Solid Mal... Cancer With A H... Epithelial Ovar... Primary Periton... Gastroesophagea... Acral Melanoma Mucosal Melanom... Cutaneous Melan... DMMR Solid Mali... Fallopian Tube ... Ovarian Cancer MSI-H Cancer DMMR Cancer Pancreas Adenoc... Skin Cancer	MDNA11 Pembrolizumab	18 Years -	Medicenna Therapeutics, Inc.
Avelumab for MSI-H or POLE Mutated Metastatic Colorectal Cancer	NCT03150706	Metastatic Colo...	Avelumab	20 Years -	Asan Medical Center
Avelumab for MSI-H or POLE Mutated Metastatic Colorectal Cancer	NCT03150706	Metastatic Colo...	Avelumab	20 Years -	Asan Medical Center

Spots Global Cancer Trial Database for mismatch repair deficient