spartalizumab (PDR001) / Novartis - LARVOL DELTA

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

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 primary completion date: May 2025 ➔ Dec 2024

Combination therapy • Metastases • 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

A Study of Select Drug Combinations in Adult Patients With Advanced/Metastatic BRAF V600 Colorectal Cancer (clinicaltrials.gov) - P1 | N=122 | Terminated | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jan 2025 ➔ Sep 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jan 2025 ➔ Sep 2024; The decision of early termination was made due to business reasons, and was not based on any safety concerns for any of the treatment combinations.

Trial completion date • Trial primary completion date • Trial termination • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • BRAF

ALTER-PATH NeoDT: Dabrafenib, Trametinib, and Spartalizumab for the Treatment of BRAF V600E or V600K Mutation Positive Stage IIIB/C/D Melanoma (clinicaltrials.gov) - P2 | N=4 | Terminated | Sponsor: M.D. Anderson Cancer Center | Completed ➔ Terminated; Study stopped due to slow enrollment

Trial termination • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor

Spartalizumab in combination with platinum-doublet chemotherapy with or without canakinumab in patients with PD-L1-unselected, metastatic NSCLC. (PubMed, BMC Cancer) - P1 | "The combination of spartalizumab and PDC, with or without canakinumab, was well tolerated across treatment groups. The antitumor activity across treatment groups was comparable with that of pembrolizumab and pemetrexed combination. Canakinumab did not appear to improve the antitumor activity when combined with spartalizumab, pemetrexed and cisplatin."

Combination therapy • Journal • Metastases • Cardiovascular • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Spartalizumab in combination with platinum-doublet chemotherapy with or without canakinumab in patients with PD-L1-unselected, metastatic NSCLC (BMC Cancer) - P1b | N=111 | NCT03064854 | Sponsor: Novartis Pharmaceuticals | "The MTD/RDE of spartalizumab was 300 mg every 3 weeks (Q3W) when administered with either gemcitabine (1250 mg/m2)/cisplatin (75 mg/m2) (group A; no dose-limiting toxicities [DLTs]), pemetrexed (500 mg/m2)/cisplatin (group B; 2 DLTs: grade 2 posterior reversible encephalopathy syndrome and grade 4 hyponatremia), or paclitaxel (200 mg/m2)/carboplatin area under the curve 6 min*mg/mL (group C; 1 DLT: grade 4 neutropenic colitis)....In groups A, B, C, and E, the overall response rates were 57.6%, 55.3%, 51.5%, and 57.1%, respectively. Group B compared with other groups had the longest median progression-free survival (10.4 months vs. 6.2–7.5 months), overall survival (29.7 months vs. 16.1–21.0 months), and duration of response (30.1 months vs. 6.0-8.2 months)."

P1 data • Non Small Cell Lung Cancer

Intratumoral STING agonist reverses immune evasion in PD-(L)1-refractory Merkel cell carcinoma: mechanistic insights from detailed biomarker analyses. (PubMed, J Immunother Cancer) - "Our results suggest that STING agonists may be able to work indirectly in MCC via signaling through immune and stromal cells in the TME, and may not necessarily need STING expression in the cancer cells. This approach may be particularly effective in tumors that are already infiltrated by inflammatory cells in the TME but are evading immune detection via HLA-I downregulation."

Biomarker • IO biomarker • Journal • Genetic Disorders • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • CD8 • STING

Trial Updates in PD-1-Resistant Melanoma (Oncology News Central) - "Alexander N. Shoushtari, MD...breaks down three important trials involving patients with melanomas that demonstrated PD-1 resistance. The IGNYTE-1 trial tested RP1, which is an injectable oncolytic virus that Dr. Shoushtari suggests 'may be a clinic option' for patients soon. The NIBIT-ML1 trial explored the addition of ASTX727 to a nivolumab-ipilimumab regimen. A separate phase 1 trial investigated the use of the PD-1 blocking agent spartalizumab with WNT974. Dr. Shoushtari takes a look at each of these studies and considers what's next for the agents involved."

Video

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 2024 ➔ May 2025 | Trial primary completion date: Dec 2024 ➔ May 2025

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

COMBI-i: A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma (clinicaltrials.gov) - P3 | N=569 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed

Combination therapy • IO biomarker • Metastases • Trial completion • Melanoma • Oncology • Solid Tumor • CD8 • PD-L1

Phase II study of PDR001 in combination with MAPK pathway inhibitors in patients with radioactive-refractory differentiated thyroid cancer (DTC) (ESMO 2024) - P2 | "We report results of a phase 2 study of either trametinib [TRM] or dabrafenib [DAB] plus anti-programmed death-1 (PD-1) antibody PDR001 in patients (pts) with radioiodine-refractory (RAIR) DTC. This is an open-label, single center study. PDR001+TRM showed efficacy in RAIR DTC lacking BRAFV600E- mut, meeting prespecified threshold for efficacy. PDR001+DAB had promising efficacy in BRAFV600E DTC, but evaluation was limited due to enrollment of just 7 pts at study completion. Further evaluation of this combination is warranted."

Clinical • Combination therapy • IO biomarker • P2 data • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • BRAF • GNAS • KRAS • NF1

A Study of Select Drug Combinations in Adult Patients With Advanced/Metastatic BRAF V600 Colorectal Cancer (clinicaltrials.gov) - P1 | N=122 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Oct 2024 ➔ Jan 2025 | Trial primary completion date: Oct 2024 ➔ Jan 2025

Metastases • Trial completion date • Trial primary completion date • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF

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

A Study of LGK974 in Patients With Malignancies Dependent on Wnt Ligands (clinicaltrials.gov) - P1 | N=185 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Breast Cancer • Cervical Cancer • Colorectal Cancer • Cutaneous Melanoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Hepatology • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • BRAF • RNF43