CA045-001: A phase III, randomized, open label study of bempegaldesleukin (NKTR-214) plus nivolumab (NIVO) versus NIVO monotherapy in patients (pts) with previously untreated, unresectable or metastatic melanoma (MEL).

TPS9601 Background: Standard of care for pts with previously untreated, unresectable or metastatic MEL includes checkpoint inhibitors. Bempegaldesleukin is a CD122-preferential IL-2 pathway agonist designed to provide sustained signaling through the IL-2 βγ receptor to activate and proliferate effector CD8+ T and NK cells over T-regulatory cells in the tumor (Hurwitz ME et al. ASCO GU 2017). In the dose-expansion phase of the phase 1/2 PIVOT-02 trial, bempegaldesleukin + NIVO was well tolerated at the recommended phase 2 dose (RP2D; bempegaldesleukin 0.006 mg/kg IV Q3W + NIVO 360 mg IV Q3W), and previously untreated pts with MEL receiving the RP2D achieved an objective response rate (ORR) of 20/38 (53%) and a complete response of 9/38 (24%) by independent radiology review (Diab A et al. SITC 2018). Presented is the design of the first phase 3 trial in the bempegaldesleukin + NIVO development program in pts with previously untreated, unresectable or metastatic MEL. Methods: This phase 3, randomized, open-label study aims to evaluate the effectiveness, safety, and tolerability of bempegaldesleukin + NIVO (NCT03635983). Eligible pts are ≥12 y with histologically confirmed stage III (unresectable) or stage IV MEL and ECOG PS ≤1 or Lansky PS ≥80% (minors 12-17 y). Pts are ineligible if they have active brain or leptomeningeal metastases, uveal MEL, or a recurrence within 6 mo of completing adjuvant treatment with any approved agent. Pts will be stratified by PD-L1 status (measured using PD-L1 IHC 28-8 pharmDx), BRAF mutation status, and lactate dehydrogenase level, and will be randomized to receive bempegaldesleukin 0.006 mg/kg IV Q3W + NIVO 360 mg IV Q3W or NIVO 360 mg IV Q3W up to 24 mo, or until progression or unacceptable toxicity (N ~ 764). Primary endpoints are ORR and progression-free survival (PFS) by blinded independent central review (BICR) and overall survival (OS). Secondary endpoints include ORR and PFS by investigator, ORR and PFS by BICR in biomarker population, OS in biomarker population, and safety. Additional endpoints include pharmacokinetics and quality-of-life assessment. Clinical trial information: NCT03635983.

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Correction to: Skin rash following Administration of Apalutamide in Japanese patients with Advanced Prostate Cancer: an integrated analysis of the phase 3 SPARTAN and TITAN studies and a phase 1 open-label study

BMC Urology ◽

10.1186/s12894-020-00739-7 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Hiroji Uemura ◽

Yosuke Koroki ◽

Yuki Iwaki ◽

Keiichiro Imanaka ◽

Takeshi Kambara ◽

...

Keyword(s):

Prostate Cancer ◽

Skin Rash ◽

Advanced Prostate Cancer ◽

Phase 1 ◽

Japanese Patients ◽

Integrated Analysis ◽

Open Label ◽

Phase 3 ◽

Open Label Study ◽

Label Study

An amendment to this paper has been published and can be accessed via the original article.

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A phase III, randomized, open-label study of isatuximab (SAR650984) plus pomalidomide (Pom) and dexamethasone (Dex) versus Pom and Dex in relapsed/refractory multiple myeloma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.tps8057 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. TPS8057-TPS8057 ◽

Cited By ~ 1

Author(s):

Paul G. Richardson ◽

Michel Attal ◽

Jesus San Miguel ◽

Frank Campana ◽

Solenn Le-Guennec ◽

...

Keyword(s):

Multiple Myeloma ◽

Disease Progression ◽

Phase 1 ◽

Unmet Need ◽

Phase Iii ◽

Tolerability Profile ◽

Open Label ◽

Open Label Study ◽

Label Study ◽

Refractory Multiple Myeloma

TPS8057 Background: Treatment for refractory or relapsed and refractory multiple myeloma (MM) remains an unmet need. Isatuximab (ISA), an anti-CD38 monoclonal antibody with multiple mechanisms of tumor killing, has shown efficacy and an acceptable tolerability profile in Phase 1/2 studies in patients with refractory or relapsed and refractory MM (RRMM) (Richter et al. ASCO 2016; Vij et al. ASCO 2016). Methods: This Phase III, prospective, multicenter, randomized, open-label study (NCT02990338; ICARIA-MM) is being conducted to evaluate the clinical benefit of ISA in combination with Pom and low-dose Dex (Pom/Dex) versus Pom/Dex for the treatment of adult patients with RRMM and demonstrated disease progression within 60 days of the last therapy, and who have received at least 2 prior lines of therapy, including lenalidomide and a proteasome inhibitor (bortezomib, carfilzomib, or ixazomib) alone or in combination. Patients will be randomly assigned in a 1:1 ratio to either ISA (10 mg/kg IV on Days 1, 8, 15, and 22 in the 1st cycle; Days 1 and 15 in subsequent cycles) plus Pom (4 mg on Days 1–21) and Dex (40 mg for patients < 75 years of age and 20 mg for patients ≥75 years of age, on Days 1, 8, 15, and 22) or Pom and Dex. Treatment cycles will be 28 days each. Patients will continue therapy until disease progression, occurrence of unacceptable adverse events (AEs), or their decision to discontinue the study, whichever comes first. The primary endpoint is progression-free survival (PFS), i.e. time from randomization to progressive disease or death from any cause. Response will be determined by IMWG criteria (2016). Key secondary endpoints include overall response rate and overall survival (OS). Safety evaluations include treatment-emergent AEs/serious AEs (including infusion-associated reactions), laboratory parameters, vital signs and assessment of physical examination. Statistical analyses will be conducted according to a pre-specified plan; approximately 300 patients (150 in each arm) are expected to be enrolled in this study. The first patient was recruited in January 2017. Study funding: Sanofi. Clinical trial information: NCT02990338.

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A phase III study of nivolumab (NIVO), NIVO + ipilimumab (IPI), or chemotherapy (CT) for microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC): Checkmate 8HW.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.tps266 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. TPS266-TPS266 ◽

Cited By ~ 1

Author(s):

Sandzhar Abdullaev ◽

Thierry André ◽

Ming Lei ◽

Heinz-Josef Lenz ◽

James Novotny ◽

...

Keyword(s):

Clinical Benefit ◽

Low Dose ◽

Group Performance ◽

Checkpoint Inhibitors ◽

Performance Status ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Phase Iii ◽

Open Label ◽

Phase 3

TPS266 Background: Patients (pts) with MSI-H/dMMR mCRC treated with CT have poorer outcomes than pts with microsatellite stable/MMR proficient mCRC. NIVO (anti–programmed death [PD]-1) and IPI (anti–cytotoxic T lymphocyte antigen-4 [CTLA-4]) are immune checkpoint inhibitors that act synergistically and promote antitumor immune response by complementary mechanisms. NIVO±IPI received accelerated US FDA approval for MSI-H/dMMR mCRC that progressed after fluoropyrimidine, oxaliplatin, and irinotecan treatment based on the phase 2, non-randomized, multicohort CheckMate 142 study. Indirect comparisons suggest that NIVO (3 mg/kg) + low-dose IPI (1 mg/kg) provides improved clinical benefit vs NIVO (investigator-assessed [INV] objective response rate [ORR] 55% vs 31%; 12-month [mo] INV progression-free survival [PFS] rate 71% vs 50%; 12-mo overall survival [OS] rate 85% vs 73%) with a favorable benefit-risk profile for previously treated MSI-H/dMMR mCRC (Overman et al. JCO 2018). NIVO+low-dose IPI also demonstrated robust and durable clinical benefit in first-line MSI-H/dMMR mCRC (INV ORR 64%; 12-mo INV PFS rate 77%; 12-mo OS rate 84%; Lenz et al. ASCO 2019, #3521). To date, no prospective phase 3 studies have reported results for anti–PD-1, anti–PD-1 + anti–CTLA-4, or CT in MSI-H/dMMR mCRC; these treatments will be evaluated in the international, multicenter, open-label, randomized, phase 3 CheckMate 8HW (NCT04008030) study. Methods: Approximately 494 pts aged ≥18 years with histologically confirmed recurrent or mCRC, irrespective of prior treatment with CT and/or targeted agents, not amenable to surgery, and with known tumor MSI-H or dMMR status, and Eastern Cooperative Oncology Group performance status ≤1 will be randomized to receive NIVO, NIVO+IPI, or investigator’s choice CT (pts in the CT arm can receive NIVO+IPI upon progression). The primary endpoint is PFS, assessed by blinded independent central review (BICR). Secondary endpoints include PFS by INV, ORR and disease control rate by BICR and INV, OS, time to and duration of response. Exploratory endpoints include safety. Clinical trial information: NCT04008030.

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