Patient case: 32-year-old female with inflammatory myofibroblastic tumor; genetic feature: RANBP2-ALK fusion

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

Summary: This is a Phase 1 first in human, open label, multi-center, dose escalation and dose expansion study to evaluate the safety, tolerability, PK, anti-tumor activity and pharmacodynamic effects of SL-279252 in subjects with advanced solid tumors or lymphomas.

Detailed description: This is a Phase 1 first in human, open label, multi-center, dose escalation and dose expansion study to evaluate the safety, tolerability, PK, anti-tumor activity and pharmacodynamic effects of SL-279252 in subjects with advanced solid tumors or lymphomas. The study design consists of Dose Escalation and Dose Expansion Cohorts. In the dose escalation phase of the study, subjects will be enrolled into sequential dose levels. During dose escalation, two possible schedules for administration of SL-279252 may be explored. The MTD or MAD may be determined for either schedule. Based on accumulating data from the dose escalation phase, including safety, PK, pharmacodynamic and anti-tumor activity, up to two dose expansion cohorts may be opened. The primary objective of the expansion phase is to further refine the safety and tolerability of SL-279252. The expansion cohorts will evaluate one or two doses of SL-279252 using one selected schedule. At the end of dose escalation and dose expansion, safety, PK, anti-tumor activity, and pharmacodynamic data will be reviewed to identify the RP2D.

Eligibility: 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, diffuse large B cell 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.
  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).
  7. Has life expectancy of greater than 12 weeks.
  8. Has adequate organ function.
  9. Females of child bearing potential (FCBP) must have a negative serum or urine pregnancy test within 72 hours of 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.
  11. All AEs resulting from prior anti-cancer immunotherapy have resolved.
  12. Recovery from toxicities from prior anti-cancer treatments including surgery, radiotherapy, chemotherapy or any other anti-cancer therapy to baseline or ≤ Grade 1.
  Exclusion Criteria:
  Participants are excluded from the study if any of the following criteria apply:
  1. Has received more than two prior checkpoint inhibitor containing treatment regimens (regimen refers to either monotherapy or combination immunotherapies).
  2. Refractory to last checkpoint inhibitor therapy defined as disease progression within 3 months of treatment initiation.
  3. Concurrent chemotherapy, immunotherapy, biologic or hormonal therapy is prohibited.
  4. Use of corticosteroids or other immunosuppressive medication, current or within 14 days of D1 of IP.

Relevance to patient case: not relevant