SL-279252 (PD1-Fc-OX40L) in Subjects With Advanced Solid Tumors or Lymphomas

Inclusion Criteria

• •Participants are eligible to be included in the study only if all the following criteria apply.
• •1. Subject has voluntarily agreed to participate by giving written informed consent in accordance with ICH/GCP guidelines and applicable local regulations.
• •2. Subject has a histologically confirmed diagnosis of one of the following unresectable locally advanced or metastatic malignancies: melanoma, non-small cell lung cancer (squamous, adeno, or adeno-squamous), urothelial cancer, squamous cell carcinoma of the head and neck, squamous cell cervical cancer, gastric or gastro-esophageal junction adenocarcinoma, squamous cell carcinoma of the anal canal, squamous cell carcinoma of the skin, renal cell cancer, Hodgkin's lymphoma, and microsatellite instability high (MSI-H) or mismatch repair deficient (MMRD) solid tumors excluding CNS malignancies. MSI and MMRD testing results as per institution is acceptable.
• •* Head and neck cancers: Subjects must have primary tumor locations in the oropharynx, oral cavity, hypopharynx, or larynx. Primary tumor sites of nasopharynx, maxillary sinus, paranasal, and unknown primary are excluded.
• •* Non-small cell lung cancers: Subjects with a known EGFR sensitizing (activating) mutation or an ALK fusion are excluded.
• •3. Subject must have received, been intolerant to, or is ineligible for standard therapy (per local guidelines and approvals) or have a malignancy for which there is no approved therapy considered standard of care.
• •4. Age 18 years and older.
• •5. Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
• •6. Has measurable disease by iRECIST (solid tumors) or RECIL 2017 (lymphoma). Refer to Appendix Sections 16.6 and 16.7 for details on criteria of measurable disease.
• •7. Has life expectancy of greater than 12 weeks.
• •8. Laboratory values must meet the following criteria. Laboratory parameter Threshold value
• •* Absolute lymphocyte count (ALC) ≥ 0.8 x 109/liter (L)
• •* Absolute neutrophil count (ANC) ≥ 1.5 x 109/L without growth factor support
• •* Platelet count ≥ 50 x 109/L
• •Laboratory parameter Threshold value
• •* Hemoglobin (Hgb) \> 9.0 g/dL with no blood transfusions for at least 5 days prior to D1 of investigational product (IP; SL-279252)
• •* Creatinine clearance (CrCl) ≥ 30 milliliter (mL)/min (modified Cockcroft-Gault)
• •* ALT/AST ≤ 3 x ULN
• •* Total bilirubin ≤ 1.5 x ULN; subjects with isolated indirect hyperbilirubinemia are permitted if direct bilirubin ratio is \<35% and total bilirubin is ≤ 3.0 x ULN
• •* Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) ≥ lower limit of normal (LLN) per institutional threshold. If LLN is not defined for a given institution, then ejection fraction must be ≥50 %.
• •9. Females of child bearing potential (FCBP) must have a negative serum or urine pregnancy test within 72 hours of D1 of IP. NOTE: FCBP unless they are surgically sterile (i.e., have undergone a complete hysterectomy, bilateral tubal ligation/occlusion, bilateral oophorectomy or bilateral salpingectomy), have a congenital or acquired condition that prevents childbearing or are naturally postmenopausal for at least 12 consecutive months (see Appendix Section 16.2 for additional details). Documentation of postmenopausal status must be provided. FCBP should use an acceptable method of contraception (see Appendix Section 16.2) to avoid pregnancy during treatment and for 30 days (which exceeds 5 half-lives) after the last dose of IP. FCBP must start using acceptable contraception at least 14 days prior to D1 of IP.
• •10. Male subjects with female partners must have azoospermia from a prior vasectomy or underlying medical condition or agree to use an acceptable method of contraception during treatment and for 30 days (which exceeds 5 half-lives) after last dose of SL-279252 (see Appendix Section 16.2). Male subjects of reproductive potential must start using acceptable contraception at least 14 days prior to D1 of treatment with SL-279252 as per Appendix Section 16.2.
• •11. All AEs resulting from prior anti-cancer immunotherapy have resolved (NOTE: exceptions include alopecia, vitiligo, and endocrinopathies adequately treated with hormone replacement).
• •8. Active pneumonitis (i.e. drug-induced, idiopathic pulmonary fibrosis, radiation-induced, etc.).
• •9. Ongoing or active infection (e.g., no systemic antimicrobial therapy for treatment of infection within 5 days of D1 of IP).
• •10. Symptomatic peptic ulcer disease or gastritis, active diverticulitis, other serious gastrointestinal (GI) disease associated with diarrhea within 6 months of D1 of IP.
• •11. Clinically significant or uncontrolled cardiac disease including any of the following:
• •* Myocarditis
• •* Unstable angina within 6 months from D1 of IP
• •* Acute myocardial infarction within 6 months from D1 of IP
• •* Uncontrolled hypertension
• •* New York Heart Association (NYHA) Class II, III or IV congestive heart failure
• •* Clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular tachycardia, second- or third- degree atrioventricular block without a pacemaker, circulatory collapse requiring vasopressor or inotropic support, or arrhythmia requiring therapy)
• •12. Untreated central nervous system (CNS) or leptomeningeal metastases. Subjects with treated CNS metastases must have completed definitive treatment (radiotherapy and/or surgery) \> 2 weeks prior to D1 of IP and no longer require steroids.
• •13. Women who are breast feeding.
• •14. Psychiatric illness/social circumstances that would limit compliance with study requirements and substantially increase the risk of AEs or compromised ability to provide written informed consent.
• •15. 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 IP.
• •16. Has undergone allogeneic stem cell transplantation or organ transplantation.
• •17. Known history or positive test for human immunodeficiency virus, or positive test for hepatitis B (positive for hepatitis B surface antigen \[HBsAg\]) or hepatitis C virus (\[HCV\]; if HCV antibody (Ab) test is positive check for HCV ribonucleic acid \[RNA\]).
• •* (NOTE: Hepatitis B virus (HBV): Subjects who are hepatitis B core antibody \[HBcAb\] positive, but HBsAg negative are eligible for enrollment. HCV: Subjects who are HCV Ab positive, but HCV RNA negative are eligible for enrollment).