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

NCT05467670 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCC 21-193
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Ovarian Cancer

Keywords

anti-CD47 therapy; platinum resistance; macrophage mediated phagocytosis; checkpoint inhibitors

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  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.

  Up to 3 years (cohort)

Secondary Outcomes (4)

• Overall Survival (OS)

  Up to 5 years

• Progression-free survival (PFS)

  Up to 5 years

• Objective response rate Immune-related Response Criteria (iRECIST)

  Up to 3 years (cohort)

• Duration of response (DOR)

  Up to 3 years (cohort); at 12 weeks (patient)

Study Arms (1)

ALX148 + Doxorubicin (PLD) + Pembrolizumab

EXPERIMENTAL

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

Drug: Pembrolizumab; Drug: ALX148; Drug: Doxorubicin

Interventions

Pembrolizumab DRUG

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.

Also known as: Keytruda®

ALX148 + Doxorubicin (PLD) + Pembrolizumab

ALX148 DRUG

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.

Also known as: evorpacept

ALX148 + Doxorubicin (PLD) + Pembrolizumab

Doxorubicin DRUG

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.

Also known as: (Pegylated Liposomal Doxorubicin (PLD)

ALX148 + Doxorubicin (PLD) + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have recurrent epithelial ovarian cancer.

You may not qualify if:

• Following histology types are acceptable: high grade serous or high grade endometrioid, clear cells, high grade translational cell, poorly differentiated or undifferentiated carcinomas, mixed histology (including one of above histology).
• prior lines in platinum-resistant setting.
• Known BRCA status or willing to be tested.
• Up to 5 prior lines of therapy are allowed.
• Participants must have measurable disease based on RECIST 1.1 with at least one target lesion.
• Participants must have an ECOG performance status of 0-1.
• Participants must be female, Age \>18 years. Because no dosing or AE data are currently available on the use of pembrolizumab in combination with ALX148 in participants ≤18 years of age, children are excluded from this study.
• Participants must have normal organ and marrow function as defined below within 14 days of enrollment unless otherwise indicated.
• Participants must have the ability to understand and the willingness to sign a written informed consent document.
• Negative serum or urine pregnancy test at screening for women of childbearing potential.
• Willing to use highly effective contraception throughout the study and for at least 4 months after last treatment administration if childbearing potential exists.
• Availability of an archival FFPE tumor tissue block from primary diagnosis specimen, metastatic, or recurrent site. If an FFPE tissue block cannot be provided then 15 unstained slides (10 microns, 10 slides minimum) will be acceptable. Please refer to the laboratory manual for complete details.
• Patients with sarcoma or carcinosarcoma or low-grade carcinoma.
• Patients with primary platinum-refractory carcinoma who progressed while on or within 3 months of primary platinum-based combination therapy at first line setting.
• Prior systemic anti-cancer therapy including investigational agents within 4 weeks \[can be in follow-up phase of prior study and could consider shorter interval for kinase inhibitors or other short half-life drugs\] prior to \[randomization /allocation\]. AEs due to previous therapies will be evaluated for eligibility. Recovery from complications due to prior must be adequate.

Sponsors & Collaborators

• Alexander B Olawaiye, MD: lead
• ALX Oncology: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

pembrolizumab; ALX148; Doxorubicin; liposomal doxorubicin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Alexander B Olawaiye, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Department of Obstetrics, Gynecology & Reproductive Sciences

Study Record Dates

• First Submitted: July 12, 2022
• First Posted: July 20, 2022
• Study Start: March 30, 2023
• Primary Completion: April 22, 2026
• Study Completion (Estimated): January 22, 2031
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)