P1, N=85, Active, not recruiting, Cue Biopharma | Trial completion date: May 2025 --> Jan 2026 | Trial primary completion date: Nov 2024 --> Jan 2026

P1, N=110, Not yet recruiting, Hoffmann-La Roche | Phase classification: P1/2 --> P1

Notably, this selective tumoral T-cell stimulation enables potent tumor-specific T-cell responses, underscoring the molecule's enhanced efficacy and safety. The AWT020 fusion protein offers a promising novel immunotherapeutic strategy by integrating PD-1 blockade and IL-2 signaling, conferring enhanced anti-tumor activity with reduced toxicity.

SHR-1916 exhibited excellent cellular selectivity, anti-tumor efficacies, and improved pharmacokinetics. It has the potential to serve as a novel immunotherapeutic agent designed to enhance IL-2's immune-stimulating activities and promote its tolerability while reducing the immunoregulatory function of Treg cells.

P1/2, N=47, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2025 --> Feb 2026

Serious TE adverse events were reported by 32.1% of TE E-ADA-positive patients, 29.0% of TE I-ADA-positive patients, 100% of E-ADA-negative patients, and 73.3% of I-ADA-negative patients. These results indicate that the presence of ADAs decreased E7777 exposure over time but did not adversely impact efficacy and safety in patients with CTCL.

Denileukin diftitox modulated regulatory T cells. However, the majority of patients experienced disease progression in the study.

P2, N=25, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2024 --> Dec 2025

P1, N=214, Not yet recruiting, Shanghai Junshi Bioscience Co., Ltd.

P1, N=40, Active, not recruiting, Cugene Inc. | Recruiting --> Active, not recruiting | Trial completion date: Jul 2024 --> Apr 2025 | Trial primary completion date: Jul 2024 --> Apr 2025

P1, N=32, Completed, Cugene Inc. | Active, not recruiting --> Completed

P1, N=61, Completed, Visterra, Inc. | Terminated --> Completed

P1/2, N=10, Not yet recruiting, Nova Scotia Health Authority | Trial completion date: Apr 2025 --> Apr 2028 | Trial primary completion date: Apr 2024 --> Apr 2028

P1, N=37, Completed, Merck Sharp & Dohme LLC

P1, N=260, Recruiting, Wuhan Union Hospital, China | Active, not recruiting --> Recruiting | N=49 --> 260 | Trial completion date: Jul 2025 --> Jul 2026

It had a favorable safety profile when administered subcutaneously on days 1, 2, 8, and 9 of each 21-day cycle as monotherapy (0.25-15 μg/kg) or combined (1.5-12 μg/kg) with the anti-PD-1 pembrolizumab (200 mg). The most frequent treatment-emergent adverse events were pyrexia, injection site reactions, and chills. Furthermore, early clinical efficacy was observed, including in immune checkpoint blockade-resistant/refractory patients.

P1/2, N=110, Not yet recruiting, Hoffmann-La Roche

P1/2, N=200, Recruiting, Krystal Biotech, Inc. | N=140 --> 200 | Trial completion date: Feb 2027 --> Feb 2028 | Trial primary completion date: Feb 2027 --> Feb 2028

P1, N=12, Not yet recruiting, City of Hope Medical Center | Initiation date: Dec 2024 --> Apr 2025

P1/2, N=240, Recruiting, Krystal Biotech, Inc. | N=140 --> 240 | Trial completion date: Jul 2026 --> Jul 2027 | Trial primary completion date: Jul 2026 --> Jul 2027

The safety profile of FAP-IL2v in combination with pembrolizumab was manageable and consistent with the known safety profile. However, further exploration of FAP-IL2v and pembrolizumab was precluded in melanoma patients with prior CPI due to the lack of clinical activity.

P2, N=88, Terminated, Maastricht University Medical Center | Active, not recruiting --> Terminated; This trial is not transitioning to the Clinical Trial Regulation (CTR) EU No 536/2014.

P1, N=30, Not yet recruiting, Otsuka Pharmaceutical Development & Commercialization, Inc.

P2, N=180, Not yet recruiting, Innovent Biologics (Suzhou) Co. Ltd.

TILT-123 therapy induced accumulation of effector lymphocytes in tumors. Peripheral lymphocyte count decrease is a promising biomarker for assessing oncolytic adenovirus therapy response.

P1, N=56, Not yet recruiting, Philogen S.p.A. | Initiation date: Dec 2024 --> May 2025

The general steps, most of which require hospital inpatient resources, include a surgical procedure to harvest sufficient tumor for TIL manufacturing, admission for non-myeloablative lymphodepleting chemotherapy followed by TIL, and intravenous interleukin-2 (IL-2, aldesleukin). Here, we provide the principles, practice, and required resources underlying the efficient and safe delivery of TIL immunotherapy derived from the clinical expertise of high-volume centers around the world. This article enhances published clinical practice guidelines by providing underlying clinical rationale and data-driven examples to demystify TIL immunotherapy in order to facilitate uptake and improve patient access to this promising treatment modality in clinical and research settings.

P2, N=296, Shanghai Pulmonary Hospital; Shanghai Pulmonary Hospital

P1, N=42, Recruiting, Synthekine | Initiation date: Dec 2024 --> Mar 2025

Immunohistochemical analysis and single-cell sequencing revealed interesting alterations in injected and noninjected tumors as well as in peripheral blood, during the treatment course, suggesting that TILT-123 facilitated TIL engraftment into the tumor, ultimately leading to a complete response. This case underscores the potential of combined immunotherapeutic approaches as a promising strategy for patients with metastatic mucosal melanoma.

P1, N=50, Recruiting, Trutino Biosciences Inc.

P1/2, N=30, Recruiting, Masonic Cancer Center, University of Minnesota | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P1, N=115, Terminated, SOTIO Biotech AG | N=200 --> 115 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2024 --> Aug 2024; Due to lack of efficacy shown at the time of the interim analysis.

P2, N=270, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Jul 2027 --> Jul 2028 | Trial primary completion date: Jan 2026 --> Apr 2027

Efficacy and safety results show that DD-cxdl would potentially fulfill a serious, unmet medical need for patients with R/R CTCL.

P1/2, N=46, Terminated, Sanofi | Active, not recruiting --> Terminated; Early discontinuation based on strategic sponsor decision not driven by any safety concerns

P1, N=84, Recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Trial completion date: Aug 2024 --> Dec 2026 | Trial primary completion date: Jun 2023 --> Jun 2026

P1, N=215, Recruiting, Hanmi Pharmaceutical Company Limited | Not yet recruiting --> Recruiting

P2, N=166, Terminated, SOTIO Biotech AG | Active, not recruiting --> Terminated; Due to lack of expected efficacy shown at the time of the interim analysis

One of the drugs inducing CADRs is aldesleukin, a recombinant interleukin-2 (recIL-2) originally approved to treat malignant melanoma and metastatic renal cell carcinoma which frequently led to skin rashes when applied in high doses for anti-cancer therapy...Together, this hypothetic irAOP forms a basis to clarify possible cellular and molecular interactions leading to recIL-2-induced skin rash. This might be used to adapt existing or develop new test systems to help predict and prevent cutaneous side effects in future IL-2-based or similar therapies.

P2, N=59, Terminated, Sanofi | Active, not recruiting --> Terminated; Early discontinuation based on strategic sponsor decision not driven by any safety concerns.

P1, N=215, Not yet recruiting, Hanmi Pharmaceutical Company Limited