spartalizumab (PDR001) / Novartis - LARVOL DELTA

Targeting Interleukin-1beta to Overcome Adaptive Immune Resistance in Renal Cell Carcinoma (KCRS 2023) - P1 | "We therefore initiated a clinical trial of neoadjuvant anti-IL1ß (canakinumab) plus anti-PD-1 (spartalizumab) in localized ccRCC. We will also identify novel immunotherapy targets in ccRCC, which will be tested in murine models and a high-throughput organoid T cell co-culture system to rapidly accelerate the development of novel combination regimens for ccRCC. This application addresses the KCRP focus on novel therapeutic targets and strategies for kidney cancer."

Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Immune Modulation • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD8 • IL1B

CDK4/6 inhibitors in low-grade serous ovarian carcinoma (LGSOC): a pooled analysis (ESGO 2026) - "MEK inhibitors (trametinib [1], selumetinib [2]) provide limited activity, while smaller studies evaluated BRAF and PI3K inhibition [3, 4]. More recently, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy have emerged as a promising strategy [5–7].Methodology A systematic search of MEDLINE, Embase, and ClinicalTrials.gov (2000–2025) identified phase I/II or basket studies evaluating palbociclib, ribociclib, or abemaciclib in LGSOC...The highest activity was observed with ribociclib + letrozole in Colon-Otero et al...2025 achieved ~ 20 % ORR, while no responses occurred in the ribociclib + spartalizumab cohort (Garrido-Castro 2025)...Reported toxicity was predominantly haematologic, consistent with the known CDK4/6-inhibitor profile.Conclusion Endocrine-based CDK4/6 inhibition shows meaningful and durable disease control in LGSOC, with benefit rates exceeding those achieved by chemotherapy. Evidence remains limited and heterogeneous; ongoing..."

Retrospective data • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor

First-in-human study of naporafenib (LXH254) with or without spartalizumab in adult patients with advanced solid tumors harboring MAPK signaling pathway alterations. (PubMed, Eur J Cancer) - "Naporafenib, with or without spartalizumab, showed an acceptable safety profile, pharmacodynamic activity and limited antitumor activity. Additional naporafenib combination therapies are currently under investigation."

Journal • Metastases • P1 data • Cardiovascular • Dermatitis • Dermatology • Heart Failure • Immunology • Lung Cancer • Melanoma • Neuralgia • Non Small Cell Lung Cancer • Oncology • Pain • Pruritus • Solid Tumor • DUSP6 • KRAS • NRAS

Phase I study of WNT974 in combination with spartalizumab in patients with cutaneous melanoma (ESMO 2024) - P1 | "WNT974 + spartalizumab was well-tolerated and demonstrated preliminary antitumor activity in pts with advanced melanoma who progressed on prior anti-PD-1-based therapy."

Clinical • Combination therapy • IO biomarker • P1 data • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor

Perioperative treatment in resectable gastric cancer with spartalizumab in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT): Results from the GASPAR phase 2 study. (PubMed, Eur J Cancer) - P2 | "Spartalizumab combined with FLOT shows high efficacy as perioperative treatment in patients with resectable gastric cancer, and an acceptable safety profile."

Journal • P2 data • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

Phase Ib study of siltuximab and spartalizumab in advanced pancreatic cancer (AACR 2024) - P1/2 | "The combination Sil/Sparta had an acceptable safety profile but did not elicit responses in advanced PDAC pts. Correlative studies using paired biopsies and blood are ongoing to determine how dual IL-6/PD-1 blockade impacts stromal and immune biomarkers in relationship to the clinical outcome measures."

IO biomarker • Metastases • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CD8 • IL6 • PD-L1

Combined PD-1, BRAF and MEK inhibition in BRAF colorectal cancer: a phase 2 trial. (PubMed, Nat Med) - P2 | "We performed a proof-of-concept single-arm phase 2 clinical trial of combined PD-1, BRAF and MEK inhibition with sparatlizumab (PDR001), dabrafenib and trametinib in 37 patients with BRAF CRC. These data suggest a potential tumor cell-intrinsic mechanism of cooperativity between MAPK inhibition and immune response, warranting further clinical evaluation of optimized targeted and immune combinations in CRC. ClinicalTrials.gov registration: NCT03668431."

Journal • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR

Efficacy of spartalizumab across multiple cancer types in patients with PD1-high mRNA expressing tumors (SOLTI-1904 ACROPOLI) (ESMO 2023) - P2 | "Premature discontinuation of the trial's recruitment occurred due to the termination of the spartalizumab development program. Nevertheless, the trial will begin enrolling a new cohort of 111 patients with PD1-high tumors with tislelizumab."

Clinical • Cholangiocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Mesothelioma • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • PD-1

SOLTI-1904 ACROPOLI TRIAL: efficacy of spartalizumab monotherapy across tumor-types expressing high levels of PD1 mRNA. (PubMed, Future Oncol) - P2 | "Primary end point is overall response rate in cohort 1. Trial registration number: NCT04802876 (ClinicalTrials.gov)."

Journal • Monotherapy • Review • Immune Modulation • Inflammation • Oncology • Solid Tumor • PD-1

Clinical and Biomarker Analysis of a Phase I/II Study of PDR001 plus Imatinib for Advanced Treatment-refractory Gastrointestinal Stromal Tumors. (PubMed, Clin Cancer Res) - "In patients with treatment-refractory GIST, PDR001 in combination with imatinib was generally tolerable, but it was not effective."

Biomarker • IO biomarker • Journal • Metastases • P1/2 data • Stroma • Tumor mutational burden • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Hematological Disorders • Oncology • Sarcoma • CD8 • TMB

Phase I study of ribociclib (CDK4/6 inhibitor) with spartalizumab (PD-1 inhibitor) with and without fulvestrant in metastatic hormone receptor-positive breast cancer or advanced ovarian cancer. (PubMed, J Immunother Cancer) - "Ribociclib with spartalizumab and fulvestrant showed limited efficacy and elevated hepatotoxicity, precluding further development. Correlative analyses revealed treatment-induced immunological effects, and genomic alterations associated with PFS."

IO biomarker • Journal • P1 data • Tumor mutational burden • Breast Cancer • Fatigue • Hematological Disorders • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Ovarian Cancer • Solid Tumor • Thrombocytopenia • CD8 • HER-2 • PD-L1 • TMB

Phase Ib/II Study of Lacnotuzumab in Combination with Spartalizumab in Patients with Advanced Malignancies. (PubMed, J Immunother Precis Oncol) - P1/2 | "However, gating criteria for efficacy were not met for expansion beyond 80 patients in phase II and the sponsor did not continue development of the combination of spartalizumab and lacnotuzumab for oncology indications. The potential signal of activity in pancreatic cancer should be further explored."

Combination therapy • Journal • Metastases • P1/2 data • Breast Cancer • Endocrine Disorders • Endometrial Cancer • Fatigue • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • CSF1

Study of Safety and Efficacy of DKY709 Alone or in Combination With PDR001 in Patients With Advanced Solid Tumors. (clinicaltrials.gov) - P1 | N=98 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Mar 2026 ➔ Oct 2026 | Trial primary completion date: Mar 2026 ➔ Oct 2026

Trial completion date • Trial primary completion date • Breast Cancer • Colorectal Cancer • Cutaneous Melanoma • Head and Neck Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Melanoma • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

SPARTO: Spartalizumab and Low-dose PAzopanib in Refractory or Relapsed Solid TumOrs of Pediatric and Adults (clinicaltrials.gov) - P1/2 | N=80 | Active, not recruiting | Sponsor: University Hospital, Bordeaux | Recruiting ➔ Active, not recruiting | N=59 ➔ 80 | Trial primary completion date: Nov 2026 ➔ Aug 2025

Enrollment change • Enrollment closed • Trial primary completion date • Pediatrics • Solid Tumor • MSI • PD-L1 • TMB

A phase 1b, multicenter, open-label dose-escalation and expansion platform study of select drug combinations in adult patients with advanced or metastatic BRAF V600 colorectal cancer (AACR-NCI-EORTC 2025) - P1 | "This first-in-human, phase 1b study (NCT04294160) evaluated the safety, pharmacokinetics (PK), and preliminary antitumor activity of several rationally designed combinations in patients with BRAF V600-mutant CRC. This open-label, adaptive platform trial included a doublet backbone arm (BA: dabrafenib [DRB436; BRAF V600 inhibitor] + LTT462 [ERK1/2 inhibitor]) and 6 triplet arms (TAs): A1 (DRB436 + LTT462 + trametinib [TMT212; MEK1/2 inhibitor]), A2 (DRB436 + LTT462 + LXH254 [B/C-RAF inhibitor]), A3 (DRB436 + LTT462 + TNO155 [SHP2 inhibitor]), A4 (DRB436 + LTT462 + spartalizumab [anti–PD-1]), A5 (DRB436 + TMT212 + TNO155), and A6 (DRB436 + LTT462 + tislelizumab [anti–PD-1]). This multi-arm platform study demonstrated manageable safety across several MAPK pathway inhibitor combinations in BRAF V600-mutant CRC. Although RDs were not defined, preliminary efficacy and disease control results showed modest antitumor effect in all treatment arms."

Clinical • IO biomarker • Late-breaking abstract • Metastases • P1 data • Colorectal Cancer • Oncology • Solid Tumor • BRAF • DUSP6

Study of Safety and Efficacy of DKY709 Alone or in Combination With PDR001 in Patients With Advanced Solid Tumors. (clinicaltrials.gov) - P1 | N=98 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Dec 2025 ➔ Mar 2026

Trial completion date • Breast Cancer • Colorectal Cancer • Cutaneous Melanoma • Head and Neck Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Melanoma • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Global safety profile of PD-1/PD-L1 inhibitors in hepatic autoimmune disorders: A global disproportionality analysis. (PubMed, Medicine (Baltimore)) - "The analysis centered on PD-1/PD-L1 inhibitors, classified by Anatomical Therapeutic Chemical codes (e.g., atezolizumab, avelumab, budigalimab, cemiplimab, dostarlimab, durvalumab, nivolumab, pembrolizumab, sintilimab, spartalizumab, and tislelizumab). Most PD-1/PD-L1 inhibitors showed pharmacovigilance signals for hepatic autoimmune disorders, particularly nivolumab and pembrolizumab. Although our findings do not permit causal inference, these findings underscore the necessity for sustained hepatic monitoring, risk stratification, and appropriate therapeutic management."

Journal • Observational data • Immunology • Oncology

PDR001 Combination Therapy for Radioiodine-Refractory Thyroid Cancer (clinicaltrials.gov) - P2 | N=19 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2025 ➔ Sep 2026 | Trial primary completion date: Sep 2025 ➔ Sep 2026

Trial completion date • Trial primary completion date • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Follicular Carcinoma • Thyroid Gland Oncocytic Carcinoma • Thyroid Gland Papillary Carcinoma

Efficacy of anti-PD1 therapy in PD1-high mRNA tumors across multiple cancer types: results from cohort 1 and cohort 2 of the phase II SOLTI-1904 ACROPOLI trial. (PubMed, ESMO Open) - "PD1 mRNA may help identify immunogenic tumors across cancer types. However, the trial's early closure and exploratory nature warrant further validation. A composite biomarker strategy integrating immune and tumor-intrinsic features may improve patient selection for ICIs."

IO biomarker • Journal • P2 data • Colorectal Cancer • Oncology • Solid Tumor • PD-L1

Trial of Anti-Tim-3 in Combination With Anti-PD-1 and SRS in Recurrent GBM (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Sep 2025 ➔ Sep 2026

Trial completion date • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • MGMT

Testing if PDR-001 Can Safely and Effectively Remove Harmful Brain Protein in Parkinson's Disease (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Ruijin Hospital

New P1 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

Focus on PD-1/PD-L1-Targeting Antibodies in Colorectal Cancer: Are There Options Beyond Dostarlimab, Nivolumab, and Pembrolizumab? A Comprehensive Review. (PubMed, Molecules) - "However, a growing number of additional PD-1/PD-L1 inhibitors, including AMP-224, atezolizumab, avelumab, camrelizumab, durvalumab, envafolimab, sintilimab, spartalizumab, tislelizumab, and toripalimab, are currently under investigation, offering new possibilities for the expansion of treatment options...Additionally, it explores key challenges such as primary and acquired resistance, limited efficacy in microsatellite-stable (MSS) CRC, and the complexities of combination strategies aimed at enhancing immunotherapeutic responses. By addressing these obstacles and highlighting prospects, this review provides insights into the evolving landscape of PD-1/PD-L1-targeted therapies in CRC and their potential to improve patient outcomes."

Journal • Review • Colorectal Cancer • Oncology • Solid Tumor • MSI

SPARC-1: A Study of Combination Spartalizumab and Canakinumab in Patients With Localized Clear Cell Renal Cell Carcinoma (clinicaltrials.gov) - P1 | N=17 | Active, not recruiting | Sponsor: Columbia University | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2026 ➔ Mar 2026 | Trial primary completion date: Dec 2025 ➔ Mar 2025

Enrollment closed • Trial completion date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD4

CDFF332A12101: DFF332 as a Single Agent and in Combination With Everolimus & Immuno-Oncology Agents in Advanced/Relapsed Renal Cancer & Other Malignancies (clinicaltrials.gov) - P1 | N=40 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Sep 2025 ➔ Mar 2026 | Trial primary completion date: Sep 2025 ➔ Mar 2026

IO biomarker • Trial completion date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Von Hippel-Lindau Syndrome • EPAS1 • SDHA • SDHAF2 • SDHB • SDHC • SDHD • VHL

Study of Safety and Efficacy of DKY709 Alone or in Combination With PDR001 in Patients With Advanced Solid Tumors. (clinicaltrials.gov) - P1 | N=98 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Sep 2025 ➔ Dec 2025 | Trial primary completion date: Sep 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • Breast Cancer • Colorectal Cancer • Cutaneous Melanoma • Head and Neck Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Melanoma • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer