Leiomyosarcoma

Background: * Fibroblast-activation protein (FAP) is a transmembrane type 2 serine protease with dipeptidyl peptidase and endopeptidase activity that is overexpressed on the surface of cancer-associated fibroblasts (CAFs), a major constituent of the tumor stroma, which correlates with a poor prognosis. * FAP-positive CAFs are present in the stromal tissue of more than 90% of epithelial carcinomas, including pancreatic, colorectal, ovarian, lung, and breast cancer among others. * FAP has emerged in recent years as a promising target for molecular imaging with PET/Computed Tomography (CT), using radiolabeled FAP inhibitors (FAPI). FAPI labeled with 68Ga or 18F has shown great promise in cancer detection demonstrating high tumor-to-background ratios in patients across a wide array of cancers. * While there is much clinical data with 68Ga-FAPI, there is much less data on the efficacy of \[18F\]FAPI-74, which is a more practical version of this PET agent due to its longer half-life. Objective: -To compare \[18F\]FAPI-74 PET imaging to 18F-fluorodeoxyglucose (18F-FDG) PET imaging and other imaging considered standard of care (SOC) (e.g., CT, and/or magnetic resonance imaging \[MRI\]) to detect sites of cancer in several malignancies. Eligibility: * \>= 18 years old. * Histologically confirmed pancreatic ductal adenocarcinoma (PDAC), cholangiocarcinoma, hepatocellular carcinoma (HCC), gastric cancer, bladder cancer, ovarian cancer, or pheochromocytoma/paraganglioma (PPGL), small cell lung or extrapulmonary neuroendocrine cancer, mesothelioma or sarcoma. * Eastern Cooperative Oncology Group (ECOG) Performance score \<= 2. Design: * This is a single-site imaging study enrolling participants with PDAC, cholangiocarcinoma, HCC, gastric cancer, bladder cancer, ovarian cancer, pheochromocytoma/paraganglioma, small cell lung or extrapulmonary neuroendocrine cancers, mesothelioma or sarcoma. * All participants will undergo baseline \[18F\]FAPI-74 PET and 18F-FDG PET imaging. * Participants with a positive baseline \[18F\]FAPI-74 PET scan (i.e., with the presence of FAPIpositive tumor/s) will undergo the second \[18F\]FAPI-74 PET imaging at the time of the next re-staging. Participants with a negative baseline \[18F\]FAPI-74 PET scan will not have post-treatment \[18F\]FAPI-74 PET or 18F-FDG PET scans performed on this protocol but will remain in follow-up. * Participants with a negative baseline 18F-FDG PET scan will not be re-scanned with 18F-FDG PET but may be re-scanned with \[18F\]FAPI-74 PET if baseline \[18F\]FAPI-74 PET imaging is positive. * All participants will be followed for 2 years following the first \[18F\]FAPI-74 PET scan to assess progression-free survival and 2-year overall survival. During this period, participants may undergo the additional \[18F\]FAPI-74 and 18F-FDG PET imaging in case of suspicion for recurrence/disease progression. These scans may be done even if the baseline \[18F\]FAPI-74 and/or 18F-FDG PET imaging are negative.

The purpose of this study is to examine the safety and efficacy of an abbreviated course of preoperative radiation, given over five days, for patients with soft tissue sarcoma of the extremity, trunk or retroperitoneum. This is in contrast to standard preoperative radiation, which is given over 25 days.

Part 1 will determine the biodistribution, dosimetry, optimal dose (radioactivity) and imaging time window of 64Cu-LNTH-1363S in 6 evaluable patients with supposed FAP-expressing solid tumors (metastatic sarcomas). All six patients will receive 8 ± 1 mCi (\~90 μg mass dose) in this study. All images will undergo analysis by blinded central readers. Optimal radioactivity and timing window will be determined based on image quality scores and measured tumor-to-background ratio. Part 1 of the study will last approximately 3 weeks for each patient and includes a Screening Period (up to 14 days), a 1-day Intervention Period and a Safety Follow-up Period (7 days post dose). Part 2 will evaluate 64Cu-LNTH-1363S correlation with FAP expression measured by IHC (SUVmax and SUVmean vs IHC score) in 20 evaluable patients with non-metastatic, operable, supposed FAP-expressing solid tumors (sarcomas, esophageal, gastric, pancreatic, colorectal) planned for surgery within 60 days (from study imaging). If the optimal radioactivity determined from Part 1 is less than 8 ± 1 mCi, the first 6 patients in Part 2 will be used to validate this optimal radioactivity. Part 2 of the study will last approximately 10 to 11 weeks and includes: a Screening Period (up to 14 days), a 1-day Intervention Period, a 1 day Safety Followup Period (Day 2) and a Scheduled Surgery IHC Sample Collection Period (from Day 2 to Day 60). Both Part 1 and Part 2 of the study will also monitor cardiac safety by detecting changes in HR, T wave, ST segment and other ECG parameters and characterizing the concentration-response relationship of 64Cu-LNTH-1363S for QT and corrected QT interval (QTc) prolongation.

PRIMARY OBJECTIVE: I. To assess the feasibility and capability of gallium Ga 68-HA-DOTA-TATE (68Ga-DOTATATE) digital positron emission tomography (dPET)/ computed tomography (CT) imaging for soft tissue sarcomas. SECONDARY OBJECTIVES: I. To evaluate the clinical benefit of 68Ga-DOTATATE for a comprehensive assessment of soft tissue sarcomas (STS) using next-generation digital PET detector technology. II. To describe the perfusion and early tumor uptake kinetics of tumor targets at baseline and following conventional systemic therapy using both 68Ga-DOT AT A TE dPET/CT and 18F-FDG dPET/CT approaches. III. Using list-mode dPET acquisitions following standard 68Ga-DOTATATE dose administrations, imaging datasets will be retrospectively generated to simulate lower dose or faster image acquisition in order to define further the minimum 68Ga-DOTATATE dose and PET image acquisition times needed to maintain lesion detectability and PET quantification. V. To assess the feasibility for 68Ga-DOTATATE dPET/CT to identify and stratify STS patients with SSTR2-positive soft tissue sarcoma lesions for future therapy planning using 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) for patients with 68Ga-DOTATATE-avid sarcomas. VI. To assess the safety of 68Ga-DOTATATE in this patient population. OUTLINE: Patients receive gallium Ga 68-HA-DOTA-TATE intravenously (IV) and undergo dPET/CT over 60 minutes up to two weeks after starting standard chemotherapy. Beginning 24 hours after gallium Ga 68-HA-DOTA-TATE dPET/CT, patients also receive fludeoxyglucose F-18 IV and undergo dPET/CT over 60 minutes.

Platelet-derived growth factor receptor α (PDGFRα) is expressed on soft tissue sarcoma (STS) where it could act as a potential therapeutic target. Olaratumab is a PDGFRα-targeted antibody that has the potential to act as the targeting moiety for both imaging and therapeutic radioisotopes. Olaratumab's demonstrated safety profile and its ability to target PDGFRα on STS cell surfaces and be rapidly internalised, make it a promising candidate for use as a radionuclide targeting agent in STS. 89Zr-TLX300-CDx is being developed for PDGFRα molecular imaging with positron emission tomography (PET) in STS. The aim of this study is to provide proof-of-concept tumour targeting of 89Zr-TLX300-CDx and assess the safety and radiation dosimetry of radiolabelled olaratumab. This study will inform future development of olaratumab as a therapeutic radiopharmaceutical agent in STS. SCHEDULE OF ASSESSMENTS Part A and B: IMAGING: 1 single injection of 89Zr-TLX300-CDx on Day 1 and whole-body imaging at 6 days ± 1 day post-injection Blood Collection for PHARMACOKINETICS: Pre-injection, 4h ± 0.5h and 6 days ± 1 day post-injection. OPTIONAL: Imaging at 4h ± 0.5h post-injection. Part C: IMAGING: 1 single injection of 89Zr-TLX300-CDx on Day 1, whole-body imaging at 24h ± 4h post-injection, whole-body imaging at 4 days ± 1 post-injection and whole-body imaging at 7 days ± 1 day post-injection Blood collection for PHARMACOKINECTCS: Pre-injection, 4h ± 0.5h, 24h ± 4h, 4 days ± 1 day and 7 days ± 1 day post-injection. OPTIONAL: Dynamic imaging 15 min ± 2 min post-injection at selected sites (extended field-of-view scanner is available), imaging at 4h ± 0.5h post-injection and imaging at 7h ± 1hpost-injection

OUTLINE: FIELD TEST: Participants complete the advance care planning (ACP) Mobility Checklist on study. Participants complete questionnaires at baseline and after completing the checklist intervention and undergo interview on study. Participants' medical records are also reviewed.

This is a Phase 1/2a, open-label, first-in-human study of T3011 given via intratumoral (IT) injection as a single agent and in combination with IV pembrolizumab in participants with advanced or metastatic solid tumors. The Phase 1 portion of the study is a single agent dose escalation which will use a 3+3 design to evaluate escalating doses of T3011. Total enrollment will depend on the toxicities and/or activity observed, with approximately 15 to 30 evaluable participants enrolled. Once the RP2D is established Phase 2a Part 1 will enroll approximately 10 participants with locally recurrent or metastatic melanoma (in Arm A) 23 to 53 participants with HNSCC in Arm B, 40 to 80 participants with sarcoma in Arm C and 10 participants with cSCC in Arm D. During Phase 2a Part 1 the safety, tolerability, and preliminary efficacy of T3011 as a single agent will be evaluated. Phase 2a Part 2 will enroll in parallel to Phase 2a Part 1 once the RP2D is established. The safety, tolerability, and preliminary efficacy of IT T3011 given in combination with IV pembrolizumab will be evaluated in 15 participants with histologically or pathologically confirmed metastatic NSCLC (Arm E). A rollover arm is also included in this study to allow participants who have documented progression on T3011 alone to receive T3011 in combination with pembrolizumab if considered eligible.

20 participants are expected to be enrolled for this open，Single-armed clinical trial to evaluate the safety and efficacy of the recombinant herpes simplex virus Ⅰ, R130 in patients with advanced solid tumors.

9 participants are expected to be enrolled for this open，Single-armed clinical trial to evaluate the safety and efficacy of the recombinant herpes simplex virus Ⅰ, R130 in patients with advanced bone and soft tissue tumors.

20 participants are expected to be enrolled for this open，Single-armed clinical trial to evaluate the safety and efficacy of the recombinant herpes simplex virus Ⅰ, R130 in patients with relapsed/refractory bone and soft tissue tumors.