Phase 2, Open-Label, Multicenter Study of Nelitolimod in Combination with Pembrolizumab in Anti-PD-1 Treatment-Naive Advanced Melanoma.

Purpose: Nelitolimod (previously SD-101) is a toll-like receptor 9 agonist. We assessed whether intratumoral nelitolimod plus pembrolizumab potentiates antitumor activity in patients with advanced melanoma who had not previously received anti-programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) therapy.

Patients And Methods: Patients with advanced melanoma who were naive to anti-PD-1/PD-L1 therapy received either nelitolimod 2 mg injected into 1-4 lesions or nelitolimod 8 mg injected weekly into a single lesion for 4 weekly doses, then every 3 weeks.

Nivolumab plus relatlimab in advanced melanoma: RELATIVITY-047 4-year update.

Background: In phase 2/3 randomized RELATIVITY-047, nivolumab plus relatlimab demonstrated a statistically significant improvement in progression-free survival (PFS), a clinically meaningful but not statistically significant improvement in overall survival (OS), and a numerically higher objective response rate (ORR) versus nivolumab alone in patients with previously untreated advanced melanoma.

Methods: Descriptive 4-year updated analyses in patients treated with nivolumab 480 mg plus relatlimab 160 mg fixed-dose combination versus nivolumab 480 mg intravenously every 4 weeks are presented. Primary endpoint was PFS by blinded independent central review (BICR).

Nivolumab With or Without Ipilimumab in Patients With Recurrent or Metastatic Merkel Cell Carcinoma: A Nonrandomized, Open-Label, International, Multicenter Phase I/II Study.

Purpose: Approximately 50% of patients with advanced Merkel cell carcinoma (MCC) have primary or acquired resistance to PD-(L)1 blockade, which may be overcome using combination immune checkpoint inhibition (ICI) with anti-cytotoxic T lymphocyte antigen-4 antibody. We present results from the recurrent/metastatic MCC cohort in CheckMate 358, a nonrandomized, multicohort, phase I/II study of nivolumab (NIVO) with or without ipilimumab (IPI) in virus-associated cancers (ClinicalTrials.gov identifier: NCT02488759).

Dual anti-CTLA-4 and anti-PD-1 blockade in metastatic basal cell carcinoma.

We report the basal cell cancer (BCC) cohort of the SWOG/NCI 1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART), a phase II prospective, multicenter basket trial of nivolumab and ipilimumab. The primary endpoint was objective response rate (ORR) (RECIST v1.1).

Three-Year Overall Survival With Nivolumab Plus Relatlimab in Advanced Melanoma From RELATIVITY-047.

Nivolumab plus relatlimab demonstrated a statistically significant improvement in progression-free survival (PFS), along with a clinically meaningful, but not statistically significant improvement in overall survival (OS) and a numerically higher objective response rate (ORR) compared with nivolumab in the RELATIVITY-047 trial (ClinicalTrials.gov identifier: NCT03470922). We report updated descriptive efficacy and safety results from RELATIVITY-047 with a median follow-up of 33.

Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma.

Background: Previous results from this trial showed longer overall survival after treatment with nivolumab plus ipilimumab or with nivolumab monotherapy than with ipilimumab monotherapy in patients with advanced melanoma. Given that patients with advanced melanoma are living longer than 7.5 years, longer-term data were needed to address new clinically relevant questions.

Nivolumab with or without ipilimumab in patients with recurrent or metastatic cervical cancer (CheckMate 358): a phase 1-2, open-label, multicohort trial.

Background: In preliminary findings from the recurrent or metastatic cervical cancer cohort of CheckMate 358, nivolumab showed durable anti-tumour responses, and the combination of nivolumab plus ipilimumab showed promising clinical activity. Here, we report long-term outcomes from this cohort.

Methods: CheckMate 358 was a phase 1-2, open-label, multicohort trial.

Overall Survival and Response with Nivolumab and Relatlimab in Advanced Melanoma.

BACKGROUND: A phase 2/3 trial — A Study of Relatlimab Plus Nivolumab Versus Nivolumab Alone in Participants With Advanced Melanoma (RELATIVITY-047) — evaluated nivolumab + relatlimab as a fixed-dose combination and found a significant progression-free survival (PFS) benefit over nivolumab monotherapy in previously untreated unresectable or metastatic melanoma. We now report updated PFS and safety data and the first results for overall survival (OS) and objective response rate (ORR). METHODS: Patients were randomly assigned 1:1 to receive nivolumab 480 mg and relatlimab 160 mg fixed-dose combination or nivolumab 480 mg alone, given intravenously every 4 weeks.

A phase 1 study of triple-targeted therapy with BRAF, MEK, and AKT inhibitors for patients with BRAF-mutated cancers.

Background: Aberrant PI3K/AKT signaling in BRAF-mutant cancers contributes to resistance to BRAF inhibitors. The authors examined dual MAPK and PI3K pathway inhibition in patients who had BRAF-mutated solid tumors (ClinicalTrials.gov identifier NCT01902173).

Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma.

Background: Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown.

Methods: In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population.

Intersection of immune and oncometabolic pathways drives cancer hyperprogression during immunotherapy.

Immune checkpoint blockade (ICB) can produce durable responses against cancer. We and others have found that a subset of patients experiences paradoxical rapid cancer progression during immunotherapy. It is poorly understood how tumors can accelerate their progression during ICB.

Treatment related toxicities with combination BRAF and MEK inhibitor therapy in resected stage III melanoma.

Unlabelled: Combination dabrafenib (D) and trametinib (T) is an FDA approved adjuvant therapy for patients with resected stage III BRAF-mutant melanoma. We describe treatment-related toxicities with adjuvant D+T in a real-world population through a retrospective case series. The primary endpoint was development of toxicities.

Early Response Assessment in Advanced Stage Melanoma Treated with Combination Ipilimumab/Nivolumab.

Background: Standard combination ipilimumab/nivolumab (I/N) is given as 4 induction doses for advanced stage melanoma followed by nivolumab single-agent maintenance therapy. While many patients receive less than 4 doses due to immune-related toxicities, it is unclear if fewer doses of I/N may still provide long term clinical benefit. Our aim is to determine if response assessment after 1 or 2 doses of I/N can predict long-term survival and assess if fewer doses of I/N can lead to similar survival outcomes.

Current State of Adjuvant Therapy for Melanoma: Less Is More, or More Is Better?

Advances in melanoma treatments over the past decade have changed the course of survival for patients. Several adjuvant therapies have been approved and are now considered standard of care for high-risk patients. These therapies have shown improvements for recurrence-free survival and distant metastases-free survival, but not overall survival, as the data are maturing.

Successful use of secukinumab in two melanoma patients with immune checkpoint inhibitor-induced inflammatory arthropathy.

Immune-related adverse events (irAEs) are a major concern when treating cancer patients with immune checkpoint inhibitor (ICI) therapy. Selecting the most appropriate management of irAEs remains an ongoing challenge because prolonged use of glucocorticoids come with their own side effects and may counteract the antineoplastic effects from immunotherapy. In this case report, we present two patients with metastatic melanoma who developed symptoms of inflammatory arthritis attributed to ICI therapy.

Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma.

Background: Lymphocyte-activation gene 3 (LAG-3) and programmed death 1 (PD-1) are distinct inhibitory immune checkpoints that contribute to T-cell exhaustion. The combination of relatlimab, a LAG-3-blocking antibody, and nivolumab, a PD-1-blocking antibody, has been shown to be safe and to have antitumor activity in patients with previously treated melanoma, but the safety and activity in patients with previously untreated melanoma need investigation.

Methods: In this phase 2-3, global, double-blind, randomized trial, we evaluated relatlimab and nivolumab as a fixed-dose combination as compared with nivolumab alone when administered intravenously every 4 weeks to patients with previously untreated metastatic or unresectable melanoma.

Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma.

Purpose: In the phase III CheckMate 067 trial, durable clinical benefit was demonstrated previously with nivolumab plus ipilimumab and nivolumab alone versus ipilimumab. Here, we report 6.5-year efficacy and safety outcomes.