BIZENGRI® for Healthcare Professionals – Information and Resources

AGAINST NRG1+ PANCREATIC

ADENOCARCINOMA AND NRG1+ NSCLC¹

BIZENGRI® is an intravenous bispecific antibody that is the first and only targeted treatment for NRG1+ pancreatic adenocarcinoma^a and NRG1+ NSCLC^a

^aAdvanced unresectable or metastatic following progression on or after prior systemic therapy.

BIZENGRI is approved by the FDA under accelerated approval and has a BOXED WARNING for Embryo-Fetal Toxicity.¹ See additional information below.

AGAINST NRG1+ PANCREATIC ADENOCARCINOMA AND
NRG1+ NSCLC¹

BIZENGRI® is an intravenous bispecific antibody that is the first and only targeted treatment for advanced unresectable or metastatic NRG1+ PDAC and NRG1+ NSCLC following progression on or after prior systemic therapy.¹

BIZENGRI is approved by the FDA under accelerated approval and has a BOXED WARNING for Embryo-Fetal Toxicity.¹ See additional information below.

BIZENGRI® is an intravenous bispecific antibody that is the first and only targeted treatment for NRG1+ pancreatic adenocarcinoma^a and NRG1+ NSCLC^a

^aAdvanced unresectable or metastatic following progression on or after prior systemic therapy.

BIZENGRI is approved by the FDA under accelerated approval and has a BOXED WARNING for Embryo-Fetal Toxicity.¹ See additional information below.

EFFICACY

Measurable and durable responses across both tumor types¹

NRG1+ PANCREATIC ADENOCARCINOMA^1,b (n=30)

NRG1+ NSCLC^1,d (n=64)

bPatients with NRG1+ pancreatic adenocarcinoma received a median of 2 prior systemic therapies (range, 0-5), with 97% of patients receiving prior systemic therapies with FOLFIRINOX, gemcitabine/taxane-based therapy, or both.¹
cConfirmed ORR assessed by blinded independent central review.¹
dPatients with NRG1+ NSCLC received a median of 2 prior systemic therapies (range, 1-6). Ninety-five percent of these patients were previously treated with platinum chemotherapy, while 64% had prior anti–PD-1 or anti–PD-L1 therapy.¹

Study design

eNRGy is a multicenter, open-label, multicohort clinical trial that enrolled adult patients with advanced or metastatic NRG1+ pancreatic adenocarcinoma or NRG1+ NSCLC who had progressed following standard-of-care treatment. A positive NRG1 gene fusion status was identified through NGS assays. Thirty patients with NRG1+ pancreatic adenocarcinoma and 64 patients with NRG1+ NSCLC received BIZENGRI 750 mg IV Q2W until unacceptable toxicity or tumor progression. The major efficacy outcome measures were confirmed ORR and DOR, determined by blinded independent central review.¹

SAFETY

Safety profile for patients with pancreatic adenocarcinoma or NSCLC in the eNRGy study¹

In the pooled safety population, there were 99 patients with NSCLC, 39 patients with pancreatic adenocarcinoma, and 37 patients with other solid tumors
The most common (≥10%) adverse reactions were diarrhea, musculoskeletal pain, fatigue, nausea, IRRs, dyspnea, rash, constipation, vomiting, abdominal pain, and edema
The most common grade 3 or 4 laboratory abnormalities (≥2%) were increased GGT, decreased hemoglobin, decreased sodium, decreased platelets, increased AST, increased ALT, increased alkaline phosphatase, decreased magnesium, decreased phosphate, increased aPTT, and increased bilirubin
The most common grade 3 or 4 adverse reactions included abdominal pain (5%), diarrhea (5%), fatigue (5%), nausea (5%), and hemorrhage (5%) in the pancreatic adenocarcinoma group, and dyspnea (5%), diarrhea (2%), and fatigue (2%) in the NSCLC group

Adverse reactions (≥10%) in patients with NRG1+ pancreatic adenocarcinoma

BIZENGRI (n=39)

Adverse reaction^e

All grades, %

Grade 3 or 4, %

Gastrointestinal disorders

Diarrhea

Nausea

Vomiting

Abdominal pain

Constipation

Abdominal distension

Stomatitis

36

23

18

15

13

10

5

2.6

5

0 Musculoskeletal and connective tissue disorders

Musculoskeletal pain^f

28

2.6 General disorders and administration site conditions

Fatigue^g

Edema^h

Pyrexia

21

13

10

5

0 Infections and infestations

COVID-19

18

0 Injury, poisoning, and procedural complications

IRRsⁱ

15

0 Vascular disorders

Hemorrhage^j

13

5 Psychiatric disorders

Anxiety

10

0 Skin and subcutaneous tissue disorders

Dry skin

10

0

eBased on NCI CTCAE v4.03 and MedDRA v26.0.
fIncludes back pain, pain in extremity, musculoskeletal chest pain, myalgia, arthralgia, noncardiac chest pain, bone pain, musculoskeletal stiffness, neck pain, and spinal pain.
gIncludes asthenia.
hIncludes peripheral edema, face edema, localized edema, and peripheral swelling.
iIncludes chills, IRR, nausea, cough, diarrhea, back pain, body temperature increased, dyspnea, face edema, fatigue, noncardiac chest pain, oropharyngeal discomfort, paresthesia, pyrexia, and vomiting.
jIncludes epistaxis, hematochezia, hematuria, and hemorrhoidal hemorrhage.

Adverse reactions (≥10%) in patients with NRG1+ NSCLC

BIZENGRI (n=99)

Adverse reaction^k

All grades, %

Grade 3 or 4, %

Gastrointestinal disorders

Diarrhea^l

Nausea

25

10

2

1 Musculoskeletal and connective tissue disorders

Musculoskeletal pain^m

23

1 Respiratory, thoracic, and mediastinal disorders

Dyspneaⁿ

Cough^o

18

15

5

1 General disorders and administration site conditions

Fatigue^p

Edema^q

17

11

2

0 Skin and subcutaneous tissue disorders

Rash^r

14

0 Injury, poisoning, and procedural complications

IRRs^s

12

0 Metabolism and nutrition disorders

Decreased appetite

11

1

kBased on NCI CTCAE v4.03 and MedDRA v26.0.
lIncludes postprocedural diarrhea.
mIncludes back pain, pain in extremity, musculoskeletal chest pain, myalgia, arthralgia, noncardiac chest pain, bone pain, musculoskeletal stiffness, neck pain, and spinal pain.
n Includes dyspnea exertional.
oIncludes productive cough.
pIncludes asthenia.
qIncludes breast edema, peripheral edema, and face edema.
rIncludes eczema, erythema, dermatitis, dermatitis contact, rash maculopapular, and rash erythematous.
sIncludes chills, IRR, nausea, cough, diarrhea, back pain, body temperature increased, dyspnea, face edema, fatigue, noncardiac chest pain, oropharyngeal discomfort, paresthesia, pyrexia, and vomiting. AEs that were considered IRRs were counted under the composite term ‘IRR,’ irrespective of the reported PT.

3^%

of patients in the NSCLC group discontinued BIZENGRI

Adverse reactions resulting in permanent discontinuation of BIZENGRI included dyspnea, pneumonitis, and sepsis (n=1 each) in the NSCLC group
Twenty-nine percent of patients with NRG1+ NSCLC experienced an adverse reaction that resulted in a dosage interruption^t
Thirty-three percent of patients with NRG1+ pancreatic adenocarcinoma experienced an adverse reaction that resulted in a dosage interruption^t

tExcludes temporary interruptions of BIZENGRI due to IRRs.

MOA

BIZENGRI is a bispecific antibody¹

BIZENGRI binds to the extracellular domains of HER2 and HER3 expressed on the cell surface, including tumor cells.

BIZENGRI inhibits HER2:HER3 dimerization and prevents NRG1 binding to HER3.

BIZENGRI decreased cell proliferation and signaling through the PI3K-AKT-mTOR pathway.

In addition, BIZENGRI mediates ADCC. BIZENGRI showed antitumor activity in mouse models of NRG1 fusion–positive lung and pancreatic cancers.

How BIZENGRI works

DOSING

Fixed biweekly dosing¹

750 mg IV

every 2 weeks

Administer the intravenous infusion over 4 hours.

750 mg IV
every 2 weeks

Administer the intravenous infusion over 4 hours.

Monitor patients closely for signs and symptoms of IRRs during the infusion and for at least 1 hour following completion of the first infusion and as clinically indicated.

Prior to each infusion, administer the following premedications to reduce the potential risk of IRRs¹:

or other anti-H1 equivalent

uOptional after initial BIZENGRI infusion.

Recommended BIZENGRI dosage modifications and management for adverse reactions

Adverse reaction

Recommendations

Grade 1, 2, or 3 IRRs

Interrupt infusion if IRR is suspected; monitor patient until symptoms resolve
Provide symptomatic treatment as needed
Resume infusion at 50% of the infusion rate at which the reaction occurred; escalate infusion rate if there are no additional symptoms
Consider premedicating with a corticosteroid for subsequent infusions

Grade 4 IRR or any grade hypersensitivity/anaphylactic reaction

Interstitial lung disease/pneumonitis

Grade 1

Grade ≥2

Left ventricular dysfunction

LVEF is 45%-49% and absolute decrease from baseline ≥10% or LVEF <45%

Interrupt BIZENGRI
Repeat LVEF assessment within 3 weeks
If LVEF is <45% or LVEF has not recovered to within 10% from baseline, permanently discontinue BIZENGRI
If LVEF is ≥50% or LVEF is 45%-49% and recovered to within 10% of baseline, resume BIZENGRI and monitor LVEF every 12 weeks while on treatment and as clinically indicated

Symptomatic CHF

Other clinically relevant adverse reactions (grade 3 or 4)

Get detailed dosing and administration information for BIZENGRI

PATIENT SUPPORT

Help your patients in their treatment journey

PTx Assist provides comprehensive access and financial support resources for eligible patients to ensure that they receive the care they need to get started and stay on BIZENGRI.^v

Terms and conditions apply. For eligible patients only.

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INDICATIONS

BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy.

BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy.

These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

BOXED WARNING: EMBRYO-FETAL TOXICITY

Embryo-Fetal Toxicity: Exposure to BIZENGRI during pregnancy can cause embryo-fetal harm. Advise patients of this risk and the need for effective contraception.

WARNINGS AND PRECAUTIONS

Infusion-Related Reactions/Hypersensitivity/Anaphylactic Reactions

BIZENGRI can cause serious and life-threatening infusion-related reactions (IRRs), hypersensitivity and anaphylactic reactions. Signs and symptoms of IRR may include chills, nausea, fever, and cough.

In the eNRGy study, 13% of patients experienced IRRs, all were Grade 1 or 2; 91% occurred during the first infusion.

Administer BIZENGRI in a setting with emergency resuscitation equipment and staff who are trained to monitor for IRRs and to administer emergency medications. Monitor patients closely for signs and symptoms of infusion reactions during infusion and for at least 1 hour following completion of first BIZENGRI infusion and as clinically indicated. Interrupt BIZENGRI infusion in patients with ≤ Grade 3 IRRs and administer symptomatic treatment as needed. Resume infusion at a reduced rate after resolution of symptoms. Immediately stop the infusion and permanently discontinue BIZENGRI for Grade 4 or life-threatening IRR or hypersensitivity/anaphylaxis reactions.

Interstitial Lung Disease/Pneumonitis

BIZENGRI can cause serious and life-threatening interstitial lung disease (ILD)/pneumonitis. In the eNRGy study, ILD/pneumonitis occurred in 2 (1.1%) patients treated with BIZENGRI. Grade 2 ILD/pneumonitis (Grade 2) resulting in permanent discontinuation of BIZENGRI occurred in 1 (0.6%) patient. Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold BIZENGRI in patients with suspected ILD/pneumonitis and administer corticosteroids as clinically indicated. Permanently discontinue BIZENGRI if ILD/pneumonitis ≥ Grade 2 is confirmed.

Left Ventricular Dysfunction

BIZENGRI can cause left ventricular dysfunction.

Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including BIZENGRI. Treatment with BIZENGRI has not been studied in patients with a history of clinically significant cardiac disease or LVEF less than 50% prior to initiation of treatment.

In the eNRGy study, Grade 2 LVEF decrease (40%-50%; 10% – 19% drop from baseline) occurred in 2% of evaluable patients. Cardiac failure without LVEF decrease occurred in 1.7% of patients, including 1 (0.6%) fatal event.

Before initiating BIZENGRI, evaluate LVEF and monitor at regular intervals during treatment as clinically indicated. For LVEF of less than 45% or less than 50% with absolute decrease from baseline of 10% or greater which is confirmed, or in patients with symptomatic congestive heart failure (CHF), permanently discontinue BIZENGRI.

Embryo-Fetal Toxicity

Based on its mechanism of action, BIZENGRI can cause fetal harm when administered to a pregnant woman. No animal reproduction studies were conducted with BIZENGRI. In postmarketing reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death. In animal models, studies have demonstrated that inhibition of HER2 and/or HER3 results in impaired embryo-fetal development, including effects on cardiac, vascular and neuronal development, and embryolethality. Advise patients of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of BIZENGRI. Advise females of reproductive potential to use effective contraception during treatment with BIZENGRI and for 2 months after the last dose.

ADVERSE REACTIONS

NRG1 Gene Fusion Positive Unresectable or Metastatic NSCLC

Serious adverse reactions occurred in 25% of patients with NRG1 Gene Fusion Positive NSCLC who received BIZENGRI. Serious adverse reactions in ≥ 2% of patients included pneumonia (n=4) dyspnea and fatigue (n=2 each). Fatal adverse reactions occurred in 3 (3%) patients and included respiratory failure (n=2), and cardiac failure (n=1). Permanent discontinuation of BIZENGRI due to an adverse reaction occurred in 3% of patients. Adverse reactions resulting in permanent discontinuation of BIZENGRI included dyspnea, pneumonitis and sepsis (n=1 each).

In patients with NRG1 Gene Fusion Positive NSCLC who received BIZENGRI, the most common (>20%) Adverse Reactions, including laboratory abnormalities, were decreased hemoglobin (35%), increased alanine aminotransferase (30%), decreased magnesium (28%), increased alkaline phosphatase (27%), decreased phosphate (26%) diarrhea (25%), musculoskeletal pain (23%), increased gamma-glutamyl transpeptidase (23%), increased aspartate aminotransferase (22%), and decreased potassium (21%).

NRG1 Gene Fusion Positive Unresectable or Metastatic Pancreatic Adenocarcinoma

Serious adverse reactions occurred in 23% of patients with NRG1 Gene Fusion Positive Pancreatic Adenocarcinoma who received BIZENGRI.

There were 2 fatal adverse reactions, one due to COVID-19 and one due to respiratory failure.

In patients with NRG1 Gene Fusion Positive Pancreatic Adenocarcinoma who received BIZENGRI the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased alanine aminotransferase (51%), diarrhea (36%), increased aspartate aminotransferase (31%), increased bilirubin (31%), decreased phosphate (31%), increased alkaline phosphatase (28%), decreased sodium (28%) musculoskeletal pain (28%), decreased albumin (26%), decreased potassium (26%), decreased platelets (26%), decreased magnesium (24%), increased gamma-glutamyl transpeptidase (23%), decreased hemoglobin (23%), vomiting (23%), nausea (23%), decreased leukocytes (21%), and fatigue (21%).

Please click here for full Prescribing Information, including BOXED WARNING.

FOR US HEALTHCARE PROFESSIONALS ONLY

FOR US HEALTHCARE PROFESSIONALS ONLY

Prescribing Information, including BOXED WARNING

Patient Site

Prescribing Information, including BOXED WARNING

Patient Site

AGAINST NRG1+ PANCREATIC

ADENOCARCINOMA AND NRG1+ NSCLC1

AGAINST NRG1+ PANCREATIC ADENOCARCINOMA AND NRG1+ NSCLC1

EFFICACY

Measurable and durable responses across both tumor types1

NRG1+ PANCREATIC ADENOCARCINOMA1,b (n=30)

NRG1+ NSCLC1,d (n=64)

SAFETY

Safety profile for patients with pancreatic adenocarcinoma or NSCLC in the eNRGy study1

Adverse reactions (≥10%) in patients with NRG1+ pancreatic adenocarcinoma

BIZENGRI (n=39)

Adverse reactione

All grades, %

Grade 3 or 4, %

Gastrointestinal disorders

Diarrhea

Nausea

Vomiting

Abdominal pain

Constipation

Abdominal distension

Stomatitis

36

23

23

18

15

13

10

5

5

2.6

5

0

0

0

Musculoskeletal and connective tissue disorders

Musculoskeletal painf

28

2.6

General disorders and administration site conditions

Fatigueg

Edemah

Pyrexia

21

13

10

5

0

0

Infections and infestations

COVID-19

18

0

Injury, poisoning, and procedural complications

IRRsi

15

0

Vascular disorders

Hemorrhagej

13

5

Psychiatric disorders

Anxiety

10

0

Skin and subcutaneous tissue disorders

Dry skin

10

0

Adverse reactions (≥10%) in patients with NRG1+ NSCLC

BIZENGRI (n=99)

Adverse reactionk

All grades, %

ADENOCARCINOMA AND NRG1+ NSCLC¹

AGAINST NRG1+ PANCREATIC ADENOCARCINOMA AND
NRG1+ NSCLC¹

Measurable and durable responses across both tumor types¹

NRG1+ PANCREATIC ADENOCARCINOMA^1,b (n=30)

NRG1+ NSCLC^1,d (n=64)

Safety profile for patients with pancreatic adenocarcinoma or NSCLC in the eNRGy study¹

Adverse reaction^e

Musculoskeletal pain^f

Fatigue^g

Edema^h

IRRsⁱ

Hemorrhage^j

Adverse reaction^k

Diarrhea^l

Musculoskeletal pain^m

Dyspneaⁿ

Cough^o

Fatigue^p

Edema^q

Rash^r

IRRs^s

3^%

BIZENGRI is a bispecific antibody¹

Fixed biweekly dosing¹

750 mg IV
every 2 weeks

Prior to each infusion, administer the following premedications to reduce the potential risk of IRRs¹: