Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Recurrence

Carcinoma

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

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Antibodies

Doxorubicin

Liposomal doxorubicin

Pembrolizumab

Immunomodulating Agents

Immunoglobulins

Immunoglobulins, Intravenous

Immunoglobulin Fc Fragments

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Given on Day 1 of each 21 day cycle, in the following order of administration:

200 mg IV pembrolizumab\* (maximum of 2 years (approximately 35 cycles)

45 mg/kg IV ALX148

30 mg/m\^2 IV doxorubicin (Pegylated Liposomal Doxorubicin (PLD)\*

\*standard of care

A type of immunotherapy that stimulates the body's immune system to fight cancer cells by targeting and blocking PD-1 proteins on the surface of certain immune T-cells, thus triggering the T-cells to find and kill cancer cells.

A fusion protein comprised of a high affinity CD47 blocker linked to an inactive immunoglobulin Fc region, enhancing innate and adaptive immune responses against cancer.

ALX148

An anthracycline that slows/stops the growth of cancer cells by blocking an enzyme called topo isomerase 2, used as second line non-platinum chemotherapy in patients with platinum-resistant ovarian cancer.

Joshua Plassmeyer

Haider Mahdi, MD

Immunotherapy with immune checkpoint inhibitors, including pembrolizumab, have emerged as a promising option in several solid cancers with durable effect and low toxicity profile. However, the benefit is limited to smaller subset of solid tumors. This trial involves the enhancement of current immune checkpoint-based immunotherapy with ALX148, an agent that inhibits CD47 (a trans-membrane protein that is highly expressed on the surface of many solid tumors as compared to normal cells).

All patients on this study will receive Pegylated Liposomal Doxorubicin (PLD) as standard of care combined with pembrolizumab and ALX148 iv every 21 days. Treatment of 45 mg/kg Q3W ALX148 in combination with pembrolizumab + chemotherapy will continue until disease progression or unacceptable grade 3/4 toxicities. For patients with a complete response to therapy, maintenance therapy with pembrolizumab and ALX148 will be continued for 12 months. Patients will have up to 4 weeks of screening, and will be treated until disease progression, patient withdraws consent, unacceptable toxicity occurs, complete response or the study is terminated. Patients may continue treatment after radiographic progression if, in the judgment of the treating investigator the patient is deriving clinical benefit from study treatment by demonstrating an absence of clinical symptoms or signs indicating clinically significant disease progression; no decline in performance status; absence of rapid disease progression or threat to vital organs or critical anatomical sites. A follow-up visit will occur within between 28 days and 35 days after the last treatment.

Safety and Efficacy of Anti-CD47, ALX148 in Combination With Liposomal Doxorubicin and Pembrolizumab in Recurrent Platinum-resistant Ovarian Cancer

Safety and Efficacy of Anti-CD47, ALX148 in Combination With Liposomal Doxorubicin and Pembrolizumab in Patients With Recurrent Platinum-resistant Ovarian Cancer: Phase II Study

The proportion of patients having either a complete response (CR) or partial response (PR), per RECIST 1.1. Complete Response (CR): Disappearance of all target lesions. For non-target lesions, CR is the disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.

The number of months from the date of study enrollment until date of death ( from any cause) or last known date of follow up if otherwise lost to follow up.

The number of months from the date of study enrollment to the date of an event of disease progression (per RECIST 1.1) or to the date of death from any cause. Progressive Disease (PD) as defined by RECIST v1.1 for target lesions: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. For non-target lesions: Appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.

The proportion of patients with complete or partial response per iRECIST. irCR (Complete Response):Disappearance of non-nodal lesions. All pathologic lymph nodes \<10 mm (2 consecutive measures ≥4 weeks apart); irPR (Partial Response):≥30% decrease from baseline (2 consecutive measures ≥4 weeks apart); All pathologic lymph nodes \<10 mm (Non-Target Lesions: Any other than disappearance of all non-nodal lesions and reduction of pathologic lymph nodes \<10 mm). Baseline tumor burden: sum of single diameters (short axis for nodal lesions, longest diameter for other lesions) for target lesions. In subsequent scans, the diameters of new measurable lesions are added to the tumor burden. Re-treatment: ≤5 target lesions (=/≠ original lesions) are selected and a new baseline tumor burden will be established.

The number of months from the date of study enrollment to the date of disease progression or death in those participants who achieve complete or partial response per RECISIT 1.1. Complete Response (CR): Disappearance of all target lesions. For non-target lesions, CR is the disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD) for target lesions: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. For non-target lesions: Appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change not a single lesion increase.

ALX Oncology

Merck Sharp & Dohme LLC

Haider Mahdi

Assistant Professor, Department of Obstetrics, Gynecology & Reproductive Sciences

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Safety and Efficacy of Anti-CD47, ALX148 in Combination With Liposomal Doxorubicin and Pembrolizumab in Recurrent Platinum-resistant Ovarian Cancer	NCT05467670	Ovarian Cancer	Pembrolizumab ALX148 Doxorubicin	18 Years -	University of Pittsburgh
Safety and Efficacy of Anti-CD47, ALX148 in Combination With Liposomal Doxorubicin and Pembrolizumab in Recurrent Platinum-resistant Ovarian Cancer	NCT05467670	Ovarian Cancer	Pembrolizumab ALX148 Doxorubicin	18 Years -	University of Pittsburgh

Spots Global Cancer Trial Database for macrophage mediated phagocytosis