spartalizumab (PDR001) / Novartis - LARVOL DELTA

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

First-in-human study of FAZ053, an anti-programmed death-ligand 1 (anti-PD-L1) monoclonal antibody, alone and in combination with spartalizumab, in patients with advanced malignancies. (PubMed, ESMO Open) - P1 | "FAZ053 monotherapy was well tolerated and effective in maintaining disease control in various tumors including ASPS and chordoma. The anticipated synergistic effect of combined programmed cell death protein 1 (PD-1) and PD-L1 inhibition was not observed. These findings contribute to the growing evidence that rare, phenotypically 'immune cold' sarcomas, such as ASPS and chordoma, can become responsive to immune checkpoint inhibitors."

IO biomarker • Journal • P1 data • Alveolar Soft Tissue Sarcoma • Chordoma • Oncology • Sarcoma • Solid Tumor

COMBI-i: A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma (clinicaltrials.gov) - P3 | N=568 | Terminated | Sponsor: Novartis Pharmaceuticals | Completed ➔ Terminated; Sponsor decision

IO biomarker • Trial termination • Melanoma • Oncology • Solid Tumor • PD-L1

PanCAN-SR1: A Phase 1B Study of Canakinumab, Spartalizumab, Nab-paclitaxel, and Gemcitabine in Metastatic Pancreatic Cancer (PC) Patients (clinicaltrials.gov) - P1 | N=10 | Completed | Sponsor: Pancreatic Cancer Action Network | Active, not recruiting ➔ Completed | Phase classification: P1b ➔ P1

Phase classification • Trial completion • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Precision Promise: A Multi-center Trial to Evaluate Multiple Regimens in Metastatic Pancreatic Cancer (clinicaltrials.gov) - P3 | N=502 | Completed | Sponsor: Pancreatic Cancer Action Network | Active, not recruiting ➔ Completed | N=825 ➔ 502 | Trial completion date: Jun 2027 ➔ Feb 2025 | Trial primary completion date: Jun 2027 ➔ Feb 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

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: May 2025 ➔ Sep 2025 | Trial primary completion date: May 2025 ➔ Sep 2025

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

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

Roll-over Study for Patients Who Have Completed a Prior Novartis-sponsored Sabatolimab (MBG453) Study and Are Judged by the Investigator to Benefit From Continued Treatment With Sabatolimab. (clinicaltrials.gov) - P2 | N=33 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Nov 2025 ➔ Feb 2028 | Trial primary completion date: Nov 2025 ➔ Feb 2028

Trial completion date • Trial primary completion date • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

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: Feb 2025 ➔ May 2025 | Trial primary completion date: Feb 2025 ➔ May 2025

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

Roll-over Study for Patients Who Have Completed a Prior Novartis-sponsored Sabatolimab (MBG453) Study and Are Judged by the Investigator to Benefit From Continued Treatment With Sabatolimab. (clinicaltrials.gov) - P2 | N=33 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=70 ➔ 33 | Trial completion date: Feb 2028 ➔ Nov 2025 | Trial primary completion date: Feb 2028 ➔ Nov 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Orphan Drug Designations and Approvals (FDA) - Generic Name: spartalizumab, Date Designated: 03/24/2021, Orphan Designation: Treatment of Pancreatic Cancer, Orphan Designation Status: Designated

Orphan drug • Pancreatic Cancer

ACROPOLI: Efficacy of Tislelizumab and Spartalizumab Across Multiple Cancer-types in Patients with PD1-high MRNA Expressing Tumors (clinicaltrials.gov) - P2 | N=184 | Active, not recruiting | Sponsor: SOLTI Breast Cancer Research Group | Recruiting ➔ Active, not recruiting

Enrollment closed • Anal Carcinoma • Biliary Cancer • Breast Cancer • Carcinosarcoma • Cervical Cancer • Cholangiocarcinoma • Clear Cell Carcinoma • Colorectal Adenocarcinoma • Colorectal Cancer • Endocrine Cancer • Epithelial Ovarian Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Eye Cancer • Gastric Adenocarcinoma • Gastric Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Adenocarcinoma • Lung Cancer • Melanoma • Mesothelioma • Microsatellite Instability • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Adenocarcinoma • Prostate Cancer • Renal Cell Carcinoma • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thyroid Gland Carcinoma • Triple Negative Breast Cancer • Urothelial Cancer • Uterine Cancer • Uveal Melanoma • PD-1

A Study of FAZ053 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies. (clinicaltrials.gov) - P1 | N=154 | Terminated | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Terminated; The early termination was based on a business decision that FAZ053 would no longer be formulated and was not a consequence of any safety concern.

Trial termination • Alveolar Soft Tissue Sarcoma • Breast Cancer • Chordoma • Oncology • Sarcoma • Solid Tumor • Triple Negative Breast Cancer

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: Feb 2025 ➔ Sep 2025 | Trial primary completion date: Feb 2025 ➔ Sep 2025

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

Nanomedicine mediated thyroid cancer diagnosis and treatment: an approach from generalized to personalized medicine. (PubMed, Discov Oncol) - "Chemotherapy includes the use of doxorubicin or taxanes generally with platinum-based drugs viz. cisplatin or carboplatin that are administered alone or along with multitarget tyrosine kinase inhibitors viz. Lenvatinib, Sorafenib, Sunitinib, Vandetanib, Pyrazolo-pyrimidine compounds, etc., single target tyrosine kinase inhibitors like Dabrafenib plus Trametinib and Vemurafenib against BRAF, Gefitinib against EGFR, Everolimus against mTOR, vascular disruptors like Fosbretabulin, and immunotherapy with viz. Spartalizumab and Pembrolizumab, are anti-PD-1/PD-L1 molecules...Hence, our review presents a closer view of NDDS as a personalized treatment for TC. We have also discussed the primary challenges facing NDDS in meeting excellence in PM."

IO biomarker • Journal • Review • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF • EGFR