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Current State of Bispecific Antibodies in B-Cell �Non-Hodgkin Lymphoma

Tycel J. Phillips, MD

Associate Professor of Medicine

City of Hope Comprehensive Cancer Center

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Disclosures

  • Research Support
    • Abbvie, Bayer, BMS, Genentech
  • Advisory Board
    • Abbvie, ADC Therapeutics, AstraZeneca, Bayer, Beigene, BMS, Genmab, Genentech, Gilead, Eli Lily, Epizyme, Incyte, Pharmacyclics, TG Therapeutics, Seattle Genetics
  • Strategic Counsel
    • Epizyme, Genmab
  • Scientific Board
    • Genentech, Merck, Genmab

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Bispecifics

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Agenda

  • DLBCL
    • Approved Agents
    • Combinations in clinical trials
  • Follicular lymphoma
    • Approved Agents
    • Clinical Trials
      • 1L
      • 2L

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DLBCL

  • Approved agents
    • Epcoritamab
    • Glofitamab
  • Investigational
    • Single agent
      • Odronextumab
    • Combinations

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EPCORE NHL-1: LBCL Expansion Cohort

Key inclusion criteria:

  • R/R CD20+ mature �B-cell neoplasm
  • ECOG PS 0–2
  • ≥2 prior lines of antineoplastic therapy, including �≥1 anti-CD20 mAb
  • FDG PET–avid and measurable disease by CT/MRI
  • Prior CAR T allowed

​

LBCL Cohort

N=157

DLBCL, HGBCL, PMBCL, and �FL Gr3B

​

    • To ensure patient safety and better characterize CRS, inpatient monitoring was required at first full dose for 24 h in this part of the study
    • Primary endpoint: ORR by independent review committee (IRC)
    • Key secondary endpoints: DOR, TTR, PFS, OS, CR rate, and safety/tolerability 

Step-up dosinga

aStep-up dosing (priming 0.16 mg and intermediate 0.8 mg dosing before first full dose) and corticosteroid prophylaxis were used to mitigate CRS. bRadiographic disease evaluation was performed every 6 wk for the first 24 wk (6, 12, 18, and 24 wk), then every 12 wk (36 and 48 wk), and every 6 mo thereafter. cMeasurable disease with CT or MRI scan with involvement of ≥2 lesions/nodes with a long axis >1.5 cm and short axis >1.0 cm (or 1 lesion/node with a long axis >2.0 cm and short axis ≥1.0 cm) and FDG PET scan that demonstrates positive lesion(s) compatible with CT-defined (or MRI-defined) anatomical tumor sites for FDG-avid lymphomas. ClinicalTrials.gov: NCT03625037. EudraCT: 2017-001748-36.

Epcoritamab SC

RP2D 48 mg

QW C1–3,

Q2W C4–9,

Q4W C10+

Treatment until PDb,c or unacceptable toxicity

Dose expansion data cutoff: January 31, 2022

Median follow-up: 10.7 mo

B-NHL:

  • No DLTs
  • MTD not reached
  • RP2D identified
  • Manageable safety profile
  • Encouraging antitumor activity

Dose escalation

DRIVE 2

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3-year Follow-Up Data

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3 year Follow Up Data

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3 year Follow Up Data

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SC Administration and Step-up Dosing May Mitigate CRS (LBCL)

CRS Events by Dosing Period

Patients (%)

Cycle 1

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Optimization

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DRIVE 1

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3-Year Follow-up

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Hutchings M et al. ASH 2023; Abstract 433.

3-Year Follow-up

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Safety

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STARGLO

DRIVE 3

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PFS/OS

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Does Region Matter??

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MOSUN/POLA

DRIVE N/A

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Response

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Safety

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Ongoing Clinical Trials

  • 1L
    • Olympia-3 (NCT06091865) - Odronextumab
    • EPCORE: DLBCL-2 (NCT05578976) – Epcoritamab
    • SKYGLO (NCT06047080) – Glofitamab
  • 2L
    • Mosun/Pola vs. R-GEMOX (NCT05171647)

​

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Follicular Lymphoma

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Mosunetuzumab

DRIVE 0

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Mosunetuzumab

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Mosunetuzumab

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Mosunetuzumab Safety (FL)

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Epcoritamab

DRIVE N/A

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Response

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Safety

  • Linton et al. ASH 2023

These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited.

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1L Therapy

DRIVE 1

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Response

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Response Cont….

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Safety

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2L+

DRIVE 1

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Response

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Response Cont….

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Conclusions

  • Multiple bispecific antibodies approved in DLBCL and FL
    • Possible approval of a third agent for both lymphoma subsets
      • Odronextumab
  • Treatment likely to move into earlier lines of therapy
    • 1st Line
      • DLBCL (multiple studies ongoing + CHOP or CHOP like backbone vs. SOC)
      • FL (Single agent or combination w/ lenalidomide)
    • 2nd Line
      • DLBCL (STARGLO, MOSUN/POLA, Epco/Len)
      • FL (Epco/Len, Mosun/Len)

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Odronextamab DLBCL Dosing

Kim WS et al. ASH 2022;Abstract 444.

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CRS

Kim WS et al. ASH 2022;Abstract 444.

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Efficacy DLBCL

Drug

N

ORR

CR

PFS (median)

DOR

Approved

Epcoritamab

157

63%

39%

4.4 m

15.6 m

Yes

Glofitamab

291

52.6%

35%

4.9 m*

18.4 m

Yes

Odronextamab

130

49.2%*

30.8%*

4.4 m

10.2 m

No

Drug

post CAR-T patients

Refractory (R)

ORR

CR

CR (R)

Epcoritamab

61

46

54%

34%

28%

Glofitamab

52

N/A

N/A

35%

N/A

Odronextamab

31

​

48.4%*

32.3%

N/A

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Odronextamab FL Dosing

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Response FL

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CRS

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Drug

N

ORR

CR

PFS 24 m

OS 24 m

mDOR

Mosunetuzumab

90

78%

60%

48%

87%

NR

Odronextamab

121

81.8%

75.2%

55.3%*

N/A

20.5 m

Epcoritamab

128

82%

63%

49.4%*

N/A

NR

Drug

DOR 12 m

DOCR 12 m

DOR 24 m

DOCR 24 m

mPFS

PFS 36 m

OS 36 m

Mosunetuzumab

67%

82%

53%*

63%

24m

43.2%

82.4%

Odronextamab

68.8%

72.2%

55%*

59.1%*

N/A

N/A

N/A

Epcoritamab

68.4%

N/A

58.4%*

72.7%*

N/A

N/A

N/A

*18 months

Summary of Response FL

*18 months

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Lymphoma Center at COH

​

  • Steve Rosen MD
  • Larry Kwak MD PhD
  • Sabarish Ayyappan MD
  • Alex Herrera MD
  • Tanya Siddiqi MD
  • Matt Mei MD
  • Elizabeth Budde MD, PhD
  • Lili Wang PhD
  • Vu Ngo PhD
  • Joo Song MD

​

​

  • Geoff Shouse MD
  • James Godfrey MD
  • John Baird MD
  • Swetha Kambhampati MD
  • Niloufer Khan MD
  • Avy Kallam MD
  • Lu Chen PhD
  • Alexey Danilov MD, PhD
  • Leslie Popplewell MD
  • CRNs and CRCs

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Questions