Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Lung Neoplasms

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma, Renal Cell

Neuroendocrine Tumors

Small Cell Lung Carcinoma

Fallopian Tube Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

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

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Fallopian Tube Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Renal Cell Carcinoma

Neuroendocrine Tumor

Small Cell Lung Cancer

Clear Cell Renal Cell Carcinoma

Fallopian Tube Cancer

Neuroepithelioma

Patients will receive escalating doses of 23ME-00610

Patients will receive the recommended dose(s) of 23ME-00610

23ME-00610

This is a first-in-human open-label Phase 1/2a study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of 23ME-00610 given by intravenous infusion in patients with advanced solid malignancies who have progressed on all available standard therapies

This study includes a dose-escalation phase in Part A to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) followed by 6 monotherapy expansion arms in Part B to further evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of 23ME-00610 in patients with solid malignancies.

5 tumor- specific monotherapy expansion cohort will enroll up to 15 patients/cohort with the following locally advanced (unresectable) or metastatic solid malignancies:

1. Clear cell renal cell carcinoma (ccRCC)
2. Epithelial ovarian, fallopian tube or primary peritoneal carcinoma
3. Neuroendocrine cancers
4. Microsatellite instability-high (MSI-H) and/or tumor mutational burden-high (TMB-H) solid cancers and
5. Extensive stage Small cell lung cancer (ES-SCLC)

A cohort of up to 8 evaluable adolescent patients with locally advanced (unresectable), or metastatic solid cancers will also be enrolled.

Approximately 15 additional evaluable patients will be added to the cohorts with Epithelial ovarian, fallopian tube or primary peritoneal carcinoma and Neuroendocrine cancers in Part B to evaluate another dose level with pharmacologic or PD evidence of therapeutic effect below the MTD/RP2D identified in Part A (for a maximum of 30 patients in total at the alternate dose).

A Phase 1/2a Study of 23ME-00610 in Patients With Advanced Solid Malignancies

A Phase 1/2a, Multicenter, Open-Label, Dose-Escalation and Expansion Study of Intravenously Administered 23ME-00610 in Patients With Advanced Solid Malignancies

ORR based on investigator assessment against RECIST 1.1 criteria

Duration of response based on investigator assessment against RECIST 1:1 criteria

Disease control rate based on investigator assessment against RECIST 1:1 criteria

Progression free survival based on investigator assessment against RECIST 1:1 criteria

23andMe, Inc.

Digestive System Diseases

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Infections

Carcinoma, Non-Small-Cell Lung

Carcinoma, Squamous Cell

Stomach Neoplasms

Breast Neoplasms

Triple Negative Breast Neoplasms

Esophageal Neoplasms

Urinary Bladder Neoplasms

Uterine Cervical Neoplasms

Melanoma

Microsatellite Instability

Squamous Cell Carcinoma of Head and Neck

Carcinoma, Basal Cell

Mesothelioma

Mesothelioma, Malignant

Skin Neoplasms

Melanoma, Cutaneous Malignant

Carcinoma, Merkel Cell

Endometrial Neoplasms

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neoplasms, Squamous Cell

Uterine Neoplasms

Uterine Diseases

Head and Neck Neoplasms

Breast Diseases

Adenoma

Neoplasms, Mesothelial

Neoplasms, Basal Cell

Communicable Diseases

Polyomavirus Infections

Virus Diseases

DNA Virus Infections

Tumor Virus Infections

Carcinoma, Neuroendocrine

Stomach Cancer

Esophageal Cancer

Malignant Mesothelioma

Merkel Cell Carcinoma

Acral Lentiginous Melanoma

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 1/2a Study of 23ME-00610 in Patients With Advanced Solid Malignancies	NCT05199272	Solid Tumor Clear Cell Rena... Epithelial Ovar... Fallopian Tube ... Primary Periton... Neuroendocrine ... MSI-H Cancer Cancer With A H... Extensive-stage...	23ME-00610	12 Years -	23andMe, Inc.
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.
A Phase 1/2a Study of 23ME-00610 in Patients With Advanced Solid Malignancies	NCT05199272	Solid Tumor Clear Cell Rena... Epithelial Ovar... Fallopian Tube ... Primary Periton... Neuroendocrine ... MSI-H Cancer Cancer With A H... Extensive-stage...	23ME-00610	12 Years -	23andMe, Inc.

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