Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma

Table 1.  Baseline Characteristics of All Enrolled Patients

Characteristic	Total (N = 41)
Median age (IQR), years	63.0 (52–70)
Male sex, No. (%)	24 (58.5)
ECOG performance status score,a No. (%)
0	32 (78.0)
1	9 (22.0)
Liver metastases present at baseline, No. (%)	11 (26.8)
PD-L1 status,b No. (%)
Negative < 1% tumor cell expression	14 (34.1)
Positive ≥ 1% tumor cell expression	24 (58.5)
Unknown	3 (7.3)
Serum LDH, No. (%)
Normal	29 (70.7)
> 1 to < 2 × ULN 4 (9.8)
≥ 2 to < 3 × ULN 4 (9.8)
≥ 3 × ULN 4 (9.8)
Stage (AJCC v7), No. (%)
M1a	5 (12.2)
M1b	16 (39.0)
M1c	20 (48.8)
BRAF mutation status, No. (%)
V600E or V600K BRAF mutation	13 (31.7)
Other BRAF mutations	2 (4.9)
Wild type	25 (61.0)
Unknown	1 (2.4)

NOTE. Data cutoff: September 1, 2020.
Abbreviations: AJCC, American Joint Committee on Cancer; ECOG, Eastern Cooperative Oncology Group; IQR, interquartile range; LDH, lactate dehydrogenase; PD-L1, programmed death-ligand 1; ULN, upper limit of normal.
^aScores on the ECOG scale range from 0 (no disability) to 5 (death).
^bPD-L1 status measured by central testing using the Dako 28–8 PharmDx assay; positive status was defined as staining on ≥ 1% of tumor cells (minimum of 100 evaluable tumor cells in the sample). In the case of insufficient tumor tissue, local pathology data were used to assess baseline PD-L1 status.

Table 2.  Incidence of Treatment-Related AEs (occurring in ≥ 10% of patients)^a

Event, No. (%)	Total, N = 41
	Grade 1–2	Grade 3–4
Treatment-related AEs	39 (95.1)	7 (17.1)
Treatment-related AEs with an incidence ≥ 10%b
Flu-like symptomsc	33 (80.5	0
Rashd	29 (70.7)	0
Fatigue	27 (65.9)	0
Pruritus	20 (48.8)	0
Arthralgia	19 (46.3)	0
Nausea	19 (46.3)	0
Decreased appetite	15 (36.6)	0
Myalgia	15 (36.6)	0
Vomiting	12 (29.3)	0
Diarrhea	11 (26.8)	0
Headache	11 (26.8)	0
Nasal congestion	11 (26.8)	0
Cough	9 (22.0)	0
Hypothyroidism	9 (22.0)	0
Hypotension	8 (19.5)	0
Peripheral edema	8 (19.5)	0
Dry skin	6 (14.6)	0
Dizziness	5 (12.2)	1 (2.4)
Oropharyngeal pain	5 (12.2)	0
Dyspnea	3 (7.3)	1 (2.4)
Acute kidney injury	0	2 (4.9)
Atrial fibrillation	0	2 (4.9)
Hypoxia	0	1 (2.4)
Hyperglycemia	0	1 (2.4)
Hypernatremia	0	1 (2.4)

NOTE. Data cutoff: September 1, 2020.
Abbreviation: AE, adverse event.
^aThe incidence of treatment-related AEs from any component of the study treatment is shown.
^bAll grade 3–4 AEs are shown with corresponding grade 1–2 incidence (even if falling less than the 10% threshold). Patients are only counted once under each preferred term using the highest grade; some patients may have experienced more than one event.
^cIncludes the following preferred terms: chills, influenza, influenza-like illness, and pyrexia.
^dIncludes the following preferred terms: erythema, rash, rash erythematous, rash generalized, rash macular, rash maculopapular, rash maculovesicular, rash papular, rash pruritic, rash pustular, rash vesicular, and exfoliative rash

Authors and Disclosures

Adi Diab, MD¹, Scott S. Tykodi, MD, PhD², Gregory A. Daniels, MD, PhD³, Michele Maio, MD⁴, Brendan D. Curti, MD⁵, Karl D. Lewis, MD⁶, Sekwon Jang, MD⁷, Ewa Kalinka, MD, PhD⁸, Igor Puzanov, MD, MSci⁹, Alexander I. Spira, MD, PhD¹⁰, Daniel C. Cho, MD¹¹, Shanhong Guan, PhD¹², Erika Puente, MD¹², Tuan Nguyen, PhD¹², Ute Hoch, PhD¹², Sue L. Currie, PhD¹², Wei Lin, MD¹², Mary A. Tagliaferri, MD¹², Jonathan Zalevsky, PhD¹², Mario Sznol, MD¹³ and Michael E. Hurwitz, MD, PhD<sup>13

1</sup>The University of Texas MD Anderson Cancer Center, Houston, TX
²University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA
³University of California, La Jolla, San Diego, CA
⁴Azienda Ospedaliera Universitaria Senese, Siena, Italy
⁵Providence Cancer Institute and Earle A. Chiles Research Institute, Portland, OR
⁶University of Colorado Cancer Center, Aurora, CO
⁷Inova Schar Cancer Institute, Fairfax, VA
⁸Polish Mother's Memorial Hospital—Research Institute, Lodz, Poland
⁹Roswell Park Comprehensive Cancer Center, Buffalo, NY
¹⁰Virginia Cancer Specialists, Fairfax, VA
¹¹Perlmutter Cancer Center at NYU Langone Medical Center, New York, NY
¹²Nektar Therapeutics, San Francisco, CA
¹³Yale School of Medicine, New Haven, CT

Corresponding Author
Adi Diab, MD, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030; e-mail: adiab@mdanderson.org.

Author Contributions
Conception and design: Adi Diab, Brendan D. Curti, Daniel C. Cho, Ute Hoch, Sue L. Currie, Wei Lin, Mary A. Tagliaferri, Jonathan Zalevsky, Michael E. Hurwitz
Administrative support: Wei Lin, Mary A. Tagliaferri, Jonathan Zalevsky
Provision of study materials or patients: Scott S. Tykodi, Gregory A. Daniels, Michele Maio, Brendan D. Curti, Alexander I. Spira, Erika Puente, Mary A. Tagliaferri, Jonathan Zalevsky, Mario Sznol, Michael E. Hurwitz
Collection and assembly of data: Adi Diab, Scott S. Tykodi, Gregory A. Daniels, Michele Maio, Brendan D. Curti, Karl D. Lewis, Sekwon Jang, Ewa Kalinka, Igor Puzanov, Alexander I. Spira, Daniel C. Cho, Shanhong Guan, Erika Puente, Ute Hoch, Sue L. Currie, Mary A. Tagliaferri, Mario Sznol, Michael E. Hurwitz
Data analysis and interpretation: Adi Diab, Scott S. Tykodi, Gregory A. Daniels, Michele Maio, Brendan D. Curti, Karl D. Lewis, Sekwon Jang, Ewa Kalinka, Igor Puzanov, Alexander I. Spira, Daniel C. Cho, Shanhong Guan, Erika Puente, Tuan Nguyen, Ute Hoch, Sue L. Currie, Wei Lin, Mary A. Tagliaferri, Jonathan Zalevsky, Mario Sznol, Michael E. Hurwitz
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors

Authors' Disclosures Of Potential Conflicts Of Interest
Disclosures provided by the authors are available with this article at DOI https://doi.org/10.1200/JCO.21.00675.

Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

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Adi Diab
Honoraria: Array BioPharma
Consulting or Advisory Role: Nektar, CureVac, Celgene, Idera
Research Funding: Nektar, Idera, Celgene, Pfizer, Merck, Apexigen
Travel, Accommodations, Expenses: Nektar

Scott S. Tykodi
Consulting or Advisory Role: Merck, Intellisphere LLC, Natera, Bristol Myers Squibb, Exelixis
Research Funding: Genentech, Bristol Myers Squibb, Merck Sharp & Dohme, Calithera Biosciences, Pfizer, Jounce Therapeutics, Nektar, Exelixis, Clinigen Group
Patents, Royalties, Other Intellectual Property: Patent pending

Gregory A. Daniels
Honoraria: Sanofi/Regeneron
Consulting or Advisory Role: Sanofi/Regeneron
Speakers' Bureau: Regeneron, Array BioPharma, Sanofi/Regeneron
Research Funding: Bristol Myers Squibb, Amgen, Viralytics, Nektar, Merck

Michele Maio
Stock and Other Ownership Interests: Theravance, Epigen Therapeutics
Honoraria: Bristol Myers Squibb, AstraZeneca, Roche, MSD, Merck, Amgen, Pierre Fabre, Alfasigma, Sanofi, Lilly
Consulting or Advisory Role: Bristol Myers Squibb, Roche, AstraZeneca, MSD, Merck, Pierre Fabre, Alfasigma
Patents, Royalties, Other Intellectual Property: DNA hypomethylating agents for cancer therapy
Travel, Accommodations, Expenses: Bristol Myers Squibb, AstraZeneca, Roche, MSD, Merck, Amgen, Pierre Fabre, Alfasigma

Brendan D. Curti
Honoraria: Clinigen Group, Nektar
Consulting or Advisory Role: Merck
Research Funding: Bristol Myers Squibb, Galectin Therapeutics, Clinigen Group
Patents, Royalties, Other Intellectual Property: Biomarkers for OX40 response
Travel, Accommodations, Expenses: Agonox

Karl D. Lewis
Honoraria: Array BioPharma, Iovance Biotherapeutics
Consulting or Advisory Role: Array BioPharma, Merck, Roche, Regeneron, Sanofi, Iovance Biotherapeutics
Research Funding: Roche/Genentech, Merck, ArrayBioPharma, Incyte, Nektar, Iovance Biotherapeutics, Bristol Myers Squibb, Kartos Therapeutics, OncoSec, Regeneron, Alkermes, Neon Therapeutics, Ultimovacs, Senhwa Biosciences, Replimune, Amgen
Travel, Accommodations, Expenses: Merck, Roche/Genentech, Regeneron, Neon Therapeutics, Alkermes
Uncompensated Relationships: Roche/Genentech, Regeneron

Sekwon Jang
Consulting or Advisory Role: Bristol Myers Squibb, EMD Serono, Novartis, Sanofi, Sun Biopharma, Genentech

Ewa Kalinka
Honoraria: BristolMyers Squibb, MSD, AstraZeneca, Regeneron, Nektar, Roche
Consulting or Advisory Role: Bristol Myers Squibb
Speakers' Bureau: Bristol Myers Squibb, Roche
Research Funding: Bristol Myers Squibb, Merck Sharp & Dohme, Nektar, AstraZeneca, Roche
Travel, Accommodations, Expenses: Roche

Igor Puzanov
Stock and Other Ownership Interests: Celldex
Consulting or Advisory Role: Amgen, Iovance Biotherapeutics, Merck, Roche, Nouscom, Seneca Therapeutics

Alexander I. Spira
Stock and Other Ownership Interests: Lilly
Honoraria: CytomX Therapeutics, AstraZeneca/MedImmune, Merck, Takeda,
Amgen, Janssen Oncology, Novartis, Bristol Myers Squibb, Bayer
Consulting or Advisory Role: Array BioPharma, Incyte, Amgen, Novartis, AstraZeneca/MedImmune, Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Merck, Bristol Myers Squibb
Research Funding: Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, LAM Therapeutics, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb, Loxo, Arch Therapeutics, Gritstone Oncology, Plexxikon, Amgen, Daiichi Sankyo, ADC Therapeutics, Janssen Oncology, Mirati Therapeutics, Rubius Therapeutics

Daniel C. Cho
Consulting or Advisory Role: Nektar, Pfizer, Werewolf Therapeutics
Expert Testimony: Genentech, Abbott/AbbVie

Shanhong Guan
Employment: Nektar Therapeutics
Stock and Other Ownership Interests: Nektar Therapeutics

Erika Puente
Employment: Nektar
Stock and Other Ownership Interests: Nektar

Tuan Nguyen
Employment: Nektar, Theravance Therapeutics
Stock and Other Ownership Interests: Nektar, Theravance

Ute Hoch
Other Relationship: Nektar

Sue L. Currie
Employment: Nektar
Stock and Other Ownership Interests: Nektar

Wei Lin
Employment: Erasca Inc, Nektar
Leadership: Erasca Inc
Stock and Other Ownership Interests: Nektar, Erasca Inc
Travel, Accommodations, Expenses: Nektar, Erasca Inc

Mary A. Tagliaferri
Employment: Nektar
Leadership: Nektar, ENZO Biochem
Stock and Other Ownership Interests: Nektar
Patents, Royalties, Other Intellectual Property: US 10576121
Travel, Accommodations, Expenses: Nektar

Jonathan Zalevsky
Employment: Nektar
Leadership: Nektar
Stock and Other Ownership Interests: Nektar
Travel, Accommodations, Expenses: Nektar

Mario Sznol
Stock and Other Ownership Interests: Amphivena, Intensity Therapeutics, Adaptive Biotechnologies, Actym Therapeutics, Torque, Nextcure, EvolveImmune Therapeutics, Johnson & Johnson/Janssen, GlaxoSmithKline
Consulting or Advisory Role: Bristol Myers Squibb, AstraZeneca/MedImmune, Nektar, Lilly, Adaptimmune, Seattle Genetics, Pierre Fabre, Molecular Partners, AbbVie, Pieris Pharmaceuticals, Innate Pharma, Immunocore, Genocea Biosciences, Anaeropharma, Zelluna, Boston Pharmaceuticals, Alligator Bioscience, Servier, Dragonfly Therapeutics, Verastem, Boehringer Ingelheim, Agenus, Numab, BioNTech AG, Genentech/Roche, Gilead Sciences, Jazz Pharmaceuticals, Targovax, Sapience Therapeutics, Pfizer, Tessa Therapeutics, OncoSec, Trillium Therapeutics, StCube, Simcha, ITeos Therapeutics
Other Relationship: Haymarket Media, Physicians' Education Resource, DAVAOncology, CEC Oncology

Michael E. Hurwitz
Employment: Pfizer, Gamida Cell, Arvinas
Consulting or Advisory Role: Nektar, Janssen, Crispr Therapeutics, Bristol Myers Squibb/Celgene, Exelixis
Research Funding: Apexigen, Astellas Pharma, AstraZeneca/MedImmune, Bayer, Bristol Myers Squibb, Corvus Pharmaceuticals, Lilly, Endocyte, Genentech, Genmab, Innocrin Pharma, Iovance Biotherapeutics, Merck, Nektar, Novartis, Pfizer, Progenics, Sanofi/Aventis, Seattle Genetics, Torque, Unum Therapeutics, Achilles Therapeutics

No other potential conflicts of interest were reported.

Sidebar

Context

Key Objective

An unmet need remains for novel immune checkpoint inhibitor combinations that achieve durable and deep responses in patients with metastatic melanoma, without adding substantial toxicity. What is the clinical efficacy and safety profile of the interleukin-2 pathway agonist bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) in previously untreated patients with metastatic melanoma from the PIVOT-02 phase II study?

Knowledge Generated

BEMPEG plus NIVO was well tolerated, and patients achieved deep and durable clinical responses, with a high rate of complete responses (34.2%) and a median progression-free survival of 30.9 months. Forty-seven percent of patients (18 of 38) achieved 100% reduction in target lesions. Exploratory on-treatment blood biomarkers were also associated with response.

Relevance

These data demonstrate encouraging safety and efficacy for this novel immunotherapy combination of BEMPEG plus NIVO in first-line metastatic melanoma. They provide rationale for the ongoing phase III study in this same patient population (PIVOT IO 001; NCT03635983).