Phase 1b Study of SL-172154 Administered With Combination Agent(s) in Subjects With Ovarian Cancers

Study SL03-OHD-105 is an open-label, multicenter, phase 1b trial designed to evaluate the safety, pharmacokinetics, pharmacodynamic effects, and preliminary anti-tumor activity of SL-172154 administered in combination with either PLD or MIRV in subjects with platinum-resistant ovarian, primary peritoneal, or fallopian tube cancers. Patients will be appropriate for combination therapy for their next line of therapy. For the SL-172154 + MIRV cohort, patients' tumors must be positive (defined as PS2+ ≥ 25%) for folate receptor alpha (FRα) as defined by the Ventana FOLR1 (Folate Receptor 1/Folate Receptor Alpha) Assay.

The first portion of the study will evaluate the safety of increasing dose levels of SL-172154 in combination with either PLD or MIRV and establish a combination dose for both regimens to be further evaluated in two dose expansion cohorts.

Inclusion criteria

• Subject has voluntarily agreed to participate by giving written informed consent in accordance with ICH/GCP guidelines and applicable local regulations.
• Age ≥18 years
• [PLD Cohort] Subject has a histologically confirmed diagnosis of high grade epithelial ovarian cancer, including primary peritoneal cancer or fallopian tube cancer. Non-epithelial tumors and ovarian tumors with low malignant potential are excluded.
• [PLD Cohort] Subject must have platinum-resistant disease, defined as radiologic disease progression within 180 days (6 months) following the last administered dose of platinum therapy. Subjects who are primary platinum-refractory, defined by progressing during or within 1 month of upfront platinum therapy, are excluded.
• [PLD Cohort] Subjects may have received any number of prior lines of therapy for epithelial ovarian cancer; however, they may not have received more than 1 prior line of systemic anticancer therapy for platinum-resistant disease.
• [MIRV Cohort] Subject has a histologically confirmed diagnosis of high grade serous epithelial ovarian cancer, including primary peritoneal cancer or fallopian tube cancer. Non-epithelial tumors and ovarian tumors with low malignant potential are excluded.
• [MIRV Cohort] Subject must have platinum-resistant disease as defined by:

• Subjects who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a response (complete response/remission [CR] or partial response/remission [PR]) and then progressed between >3 months and ≤6 months after the date of the last dose of platinum.
• Subjects who have received 2 or 3 lines of platinum therapy must have progressed on or within 6 months after the date of the last dose of platinum.
• Subjects who are platinum refractory during front-line treatment are excluded [primary platinum-refractory disease, defined as disease that did not respond to (CR or PR) or has progressed within 3 months of the last dose of first-line platinum-containing chemotherapy]
• [MIRV Cohort] Subjects must have received at least 1 but no more than 3 prior systemic lines of anticancer therapy.
• [MIRV Cohort] Willing to provide an archival tumor tissue block or slides or undergo procedure to obtain new biopsy using a low-risk, medically routine procedure for IHC confirmation of FRα positivity.
• [MIRV Cohort] Subject's tumor must be positive for FRα expression (defined as PS2+ ≥ 25% by the Ventana FOLR1 Assay).
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
• Measurable disease by RECIST v1.1 using radiologic assessment.
• Adequate organ and hematologic function
• Subjects must have stabilized or recovered (Grade 1 or baseline) from all prior anti-cancer therapy-related toxicities.
• [MIRV Cohort, Dose Expansion only] Willing to consent to 1 mandatory pre-treatment and 1 on-treatment tumor biopsy, unless there is excessive risk from the procedure as determined by the investigator

Exclusion criteria

• Prior treatment with a signal-regulatory protein alpha (SIRPα) targeting agent, anti-CD47 agent or CD40 agonist.
• [PLD Cohort] Prior treatment with doxorubicin or PLD
• [MIRV Cohort] Prior treatment with MIRV or another FRα-targeting agent
• Any anti-cancer therapy within the time intervals specified per protocol.
• Concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment is prohibited.
• Receipt of live attenuated vaccine (including live attenuated vaccines for COVID-19) within 28 days of the first dose of study treatment.
• Current or prior use of systemic immunosuppressive medication within 7 days prior to first dose of study treatment.
• [MIRV Cohort] Requires use of folate-containing supplements (e.g., folate deficiency)
• Active or documented history of autoimmune disease that has required treatment with a disease modifying agent or immunosuppressive therapy in the past two years, history of multiple sclerosis (MS) or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome). Exceptions include controlled Type I diabetes, vitiligo, alopecia areata or hypo/hyperthyroidism.
• Ongoing or active infection (e.g., no systemic antimicrobial therapy for treatment of infection within 5 days of D1 of study treatment).
• Known severe hypersensitivity to the active drug substance or to any of the excipients for the agents to be administered or known hypersensitivity to Chinese hamster ovary cell products.
• Severe gastrointestinal conditions.
• Clinically significant or uncontrolled cardiovascular disease
• [MIRV Cohort] History of cirrhotic liver disease (Child-Pugh Class B or C)
• [MIRV Cohort] Active or chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/monitoring, such as uncontrolled glaucoma, wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, macular degeneration, presence of papilledema, and/or monocular vision.
• Previous clinical diagnosis of noninfectious interstitial lung disease (ILD), including noninfectious pneumonia.
• Untreated central nervous system or leptomeningeal metastases.
• Another malignancy that requires active therapy and that, in the opinion of the investigator and Sponsor, would interfere with monitoring of radiologic assessments of response to the study treatment.
• Has undergone allogeneic stem cell transplantation or organ transplantation.
• Known history or positive test for human immunodeficiency virus (HIV), or positive test for hepatitis B (positive for hepatitis B surface antigen [HBsAg]) or hepatitis C virus ([HCV]