Drug Trials Snapshots: BIZENGRI

HOW TO USE THIS SNAPSHOT 
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT 
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.

Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the BIZENGRI Prescribing Information for all of the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).

Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).

Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).

BIZENGRI (zenocutuzumab-zbco)
(bi zen gree ) 
Merus N.V. 
Approval date: December 4, 2024

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DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

BIZENGRI is a prescription medicine used to treat:

• Adults with non-small cell lung cancer (NSCLC) that has an NRG1 gene fusion (NRG1-positive) and cannot be removed by surgery (unresectable) or has spread to other parts of the body
• Adults with pancreatic adenocarcinoma that has an NRG1 gene fusion (NRG1-positive) and cannot be removed by surgery (unresectable) or has spread to other parts of the body

BIZENGRI should be used in patients who have been previously treated with chemotherapy and other anticancer agents.

How is this drug used?

BIZENGRI is given as an intravenous (IV) infusion into your vein every two weeks.

Who participated in the clinical trials?

The FDA approved BIZENGRI based on evidence from one clinical trial (NCT02912949/eNRGy) in 99 adult patients with NRG1-positive NSCLC and in 39 adult patients with NRG1-positive pancreatic adenocarcinoma. The trial was conducted at 65 sites in 18 countries including the United States, the United Kingdom, Canada, the European Union, Israel, Japan, Singapore, South Korea, and Taiwan. There were 27 patients with NRG1-positive NSCLC treated in the United States and 72 treated outside the United States. There were 18 patients with NRG1-positive pancreatic adenocarcinoma treated in the United States and 21 treated outside the United States.

The safety and efficacy of BIZENGRI were both assessed using information from the eNRGy trial; however, the number of patients shown in the description of efficacy findings may differ from the number of patients shown in the description of safety findings due to the different inclusion criteria used to assess efficacy.

The safety of BIZENGRI was evaluated in two groups of patients in the eNRGy trial:

• The safety of BIZENGRI was evaluated in 99 patients with NRG1-positive NSCLC who received at least one dose at the recommended phase 2 dose in the eNRGy trial. The median age of patients who received BIZENGRI was 66 years (range: 27 to 88), 54% were 65 years or older; 62% were female; 37% were White, 53% were Asian, 2% were Black or African American; and 1% were Hispanic or Latino.
• The safety of BIZENGRI was evaluated in 39 patients with NRG1-positive pancreatic adenocarcinoma who received at least one dose at the recommended phase 2 dose in the eNRGy trial. The median age was 51 years (range: 21 to 74), 23% were 65 years or older; 49% were female; 82% were White, 13% were Asian, 2.6% were Black or African American; and 5% were Hispanic or Latino.

The efficacy of BIZENGRI was evaluated in two groups of patients in the eNRGy trial:

• The efficacy of BIZENGRI was evaluated in 64 NRG1-positive NSCLC patients previously treated with systemic therapy. Characteristics of this group are as follows: median age 63.5 years (range: 32 to 86) with 47% of patients ≥65 years of age; 64% female; 56% Asian, 33% White, and 11% other races or not reported; none were Hispanic or Latino.
• The efficacy of BIZENGRI was evaluated in 30 NRG1-positive pancreatic adenocarcinoma patients. Characteristics of this group are as follows: median age 49 years (range: 21 to 72) with 10% of patients ≥65 years of age; 43% female; 87% White, 7% Asian, 3% Black or African American, 3% other races or not reported; and 3% were Hispanic or Latino.

How were the trials designed?

BIZENGRI was evaluated in one clinical trial (eNRGy). All patients received BIZENGRI as an intravenous infusion every two weeks until either cancer progression or intolerable side effects.

The benefit of BIZENGRI was evaluated by measuring the percentage of patients who had complete or partial shrinkage of their tumors (overall response rate or ORR) and by measuring the duration of that benefit (duration of response or DOR).

How were the trials designed?

The eNRGy study was a multicenter, open-label, multi-cohort clinical study enrolling patients with NRG1 fusion-positive NSCLC and pancreatic adenocarcinoma. Identification of positive NRG1 gene fusion status was determined based on next generation sequencing (NGS). Patients received BIZENGRI as an intravenous infusion, 750 mg every two weeks, until unacceptable toxicity or disease progression. Tumor assessments were performed every eight weeks. The benefit of BIZENGRI was assessed by measuring the percentage of patients who had complete or partial shrinkage of their tumors (ORR) and by measuring the duration of that benefit (DOR) as determined by a blinded independent central review.

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DEMOGRAPHICS SNAPSHOT

NRG1-Positive NSCLC

Figure 1 summarizes how many male and female NRG1-positive NSCLC patients previously treated with systemic therapy were enrolled in the clinical trial used to evaluate the efficacy of BIZENGRI.

Figure 1. Baseline Demographics by Sex for NRG1-Positive NSCLC Patients, Efficacy Population

 

Source: Adapted from FDA Review

Figure 2 summarizes the percentage of NRG1-positive NSCLC patients previously treated with systemic therapy by race enrolled in the clinical trial used to evaluate the efficacy of BIZENGRI.

Figure 2. Baseline Demographics by Race for NRG1-Positive NSCLC Patients, Efficacy Population

Source: Adapted from FDA Review

Figure 3 summarizes the percentage of NRG1-positive NSCLC patients previously treated with systemic therapy by age enrolled in the clinical trial used to evaluate the efficacy of BIZENGRI.

Figure 3. Baseline Demographics by Age for NRG1-Positive NSCLC Patients, Efficacy Population

Source: Adapted from FDA Review

Figure 4 summarizes the percentage of NRG1-positive NSCLC patients previously treated with systemic therapy by ethnicity enrolled in the clinical trial used to evaluate the efficacy of BIZENGRI.

Figure 4. Baseline Demographics by Ethnicity for NRG1-Positive NSCLC Patients, Efficacy Population

Source: Adapted from FDA Review

NRG1-Positive Pancreatic Adenocarcinoma

Figure 5 summarizes how many male and female NRG1-positive pancreatic adenocarcinoma patients previously treated with systemic therapy were enrolled in the clinical trial used to evaluate the efficacy of BIZENGRI.

Figure 5. Baseline Demographics by Sex for NRG1-Positive Pancreatic Adenocarcinoma Patients, Efficacy Population

Source: Adapted from FDA Review

Figure 6 summarizes the percentage of NRG1-positive pancreatic adenocarcinoma patients by race enrolled in the clinical trial used to evaluate the efficacy of BIZENGRI.

Figure 6. Baseline Demographics by Race for NRG1-Positive Pancreatic Adenocarcinoma Patients, Efficacy Population

Source: Adapted from FDA Review

Figure 7 summarizes the percentage of NRG1-positive pancreatic adenocarcinoma patients previously treated with systemic therapy by age enrolled in the clinical trial used to evaluate the efficacy of BIZENGRI.

Figure 7. Baseline Demographics by Age for NRG1-Positive Pancreatic Adenocarcinoma Patients, Efficacy Population

Source: Adapted from FDA Review

Figure 8 summarizes the percentage of NRG1-positive pancreatic adenocarcinoma patients previously treated with systemic therapy by ethnicity enrolled in the clinical trial used to evaluate the efficacy of BIZENGRI.

Figure 8. Baseline Demographics by Ethnicity for NRG1-Positive Pancreatic Adenocarcinoma Patients, Efficacy Population

Source: Adapted from FDA Review

Who participated in the trials?

Table 1. Baseline Demographics of Advanced Unresectable or Metastatic NRG1-Positive NSCLC, Efficacy Population

Demographic	BIZENGRI N=64 n (%)
Sex
Male	23 (36)
Female	41 (64)
Age group, years
18 to <65	34 (53)
≥65	30 (47)
Race
White	21 (33)
Asian	36 (56)
Other	2 (3)
Not reported	5 (8)
Ethnicity
Not Hispanic or Latino	56 (87)
Not reported or unknown	8 (13)

Source: Adapted from FDA Review
Abbreviations: NSCLC, non-small cell lung cancer

Table 2. Baseline Demographics of Advanced Unresectable or Metastatic NRG1-Positive Pancreatic Adenocarcinoma, Efficacy Population

Demographic	BIZENGRI N=30 n (%)
Sex
Male	17 (57)
Female	13 (43)
Age group, years
18 to <65	27 (90)
≥65	3 (10)
Race
White	26 (87)
Black or African American	1 (3)
Asian	2 (7)
Not reported	1 (3)
Ethnicity
Hispanic or Latino	1 (4)
Not Hispanic or Latino	28 (93)
Not reported or unknown	1 (4)

Source: Adapted from FDA Review

What are the benefits of this drug?

BIZENGRI was approved under FDA’s accelerated approval program, which provides earlier patient access to a promising new drug while the company continues to conduct clinical trials to confirm that the drug works well.

In the trial, 33% of 64 patients with NRG1-positive NSCLC experienced complete or partial shrinkage of their tumors; 43% of these patients had complete or partial shrinkage of their tumors which lasted more than six months.

In the trial, 40% of 30 patients with NRG1-positive pancreatic adenocarcinoma experienced complete or partial shrinkage of their tumors; 67% of these patients had complete or partial shrinkage of their tumors which lasted more than six months.

What are the benefits of this drug (results of trials used to assess efficacy)?

Table 3 and Table 4 summarize the results of the major efficacy outcome measures, ORR, and DOR as determined by blinded independent central review according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Table 3. Efficacy Results for Advanced Unresectable or Metastatic NRG1-Positive Previously Treated NSCLC in the eNRGy Study

Efficacy Parameter	BIZENGRI N=64
Overall response rate1, % (95% CI)	33 (22, 46)
Complete response rate, %	1.6
Partial response rate, %	31
Duration of response
Median (95% CI) (months)	7.4 (4.0, 16.6)
Patients with DOR ≥6 months2, %	43

Source: Adapted from BIZENGRI Prescribing Information
¹ Confirmed overall response rate assessed by blinded independent central review
² Based on observed duration of response
Abbreviations: CI, confidence interval; DOR, duration of response; NSCLC, non-small cell lung cancer

Table 4. Efficacy Results for Advanced Unresectable or Metastatic NRG1-Positive Pancreatic Adenocarcinoma in the eNRGy Study

Efficacy Parameter	BIZENGRI N=30
Overall response rate1, % (95% CI)	40 (23, 59)
Complete response rate, %	3.3
Partial response rate, %	37
Duration of response
Range (months)	3.7, 16.6
Patients with DOR ≥6 months2, %	67

Source: Adapted from BIZENGRI Prescribing Information
¹ Confirmed overall response rate assessed by blinded independent central review
² Based on observed duration of response
Abbreviations: CI, confidence interval; DOR, duration of response

Were there any differences in how well the drug worked in clinical trials among sex, race, and age?

NRG1-Positive NSCLC

• Sex: BIZENGRI worked similarly in males and females.
• Race: BIZENGRI worked similarly in Asian and White patients. The number of patients of other races was small; therefore, differences in how the drug worked in other races could not be determined.
• Age: BIZENGRI worked similarly in patients younger and older than 65 years of age.

NRG1-Positive Pancreatic Adenocarcinoma

• Sex: BIZENGRI worked similar in males and females.
• Race: The number of patients of races other than White was small; therefore, differences in how BIZENGRI worked among races could not be determined.
• Age: The number of patients older than 65 years of age was limited; therefore, differences in how BIZENGRI worked between age groups could not be determined.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

Table 5 summarizes ORR by age, sex and race subgroups for previously treated NSCLC, and Table 6 summarizes ORR by age and sex subgroups for pancreatic adenocarcinoma.

Table 5. Efficacy Results by Subgroup for Advanced Unresectable or Metastatic NRG1-Positive Previously Treated NSCLC in the eNRGy Study

Subgroup	BIZENGRI, N=64
	n	ORR, % (95% CI)
Overall	64	32.8 (22; 46)
Age, years
<65	34	27 (13; 44)
≥65	30	40 (23; 59)
Sex
Male	23	39 (20, 62)
Female	41	29 (16; 46)
Race
White	21	24 (8; 47)
Asian	36	33 (19; 51)
Other	2	100 (16; 100)
Not reported	5	40 (5, 85)

Source: Adapted from FDA Review
Abbreviations: CI, confidence interval; NSCLC, non-small cell lung cancer; ORR, overall response rate

Table 6. Efficacy Results by Subgroup¹ for Advanced Unresectable or Metastatic NRG1-Positive Pancreatic Adenocarcinoma in the eNRGy Study

Subgroup	BIZENGRI, N=30
	n	ORR, % (95% CI)
Overall	30	40 (23; 59)
Age, years
<65	27	33 (17; 54)
≥65	3	100 (29; 100)
Sex
Male	17	41 (18; 67)
Female	13	39 (14; 68)

Source: Adapted from FDA Review
¹ Due to limited sample size in races other than White, no analysis by race was conducted for pancreatic adenocarcinoma patients
Abbreviations: CI, confidence interval; ORR, overall response rate

What are the possible side effects?

BIZENGRI may cause serious side effects including infusion-related, allergic, and anaphylactic reactions; lung problems; heart problems that may affect your heart’s ability to pump blood; and harm to unborn babies.

The most common side effects observed with BIZENGRI include diarrhea, muscle or bone pain, tiredness, nausea, shortness of breath, rash, constipation, vomiting, stomach-area (abdominal) pain, and swelling of different areas of the body.

Please refer to the Patient Information for additional information.

What are the possible side effects (results of trials used to assess safety)?

Table 7 through Table 10 summarize the adverse reactions and laboratory abnormalities that occurred in patients with NRG1-positive NSCLC and pancreatic adenocarcinoma treated with BIZENGRI.

Table 7. Adverse Reactions (≥10%) in Patients With NRG1-Positive NSCLC Who Received BIZENGRI in the eNRGy Study, Safety Population

Adverse Reaction1	BIZENGRI, N=99
	All Grades %	Grade 3 or 4 %
Gastrointestinal disorders
Diarrhea2	25	2
Nausea	10	1
Musculoskeletal and connective tissue disorders
Musculoskeletal pain3	23	1
Respiratory, thoracic and mediastinal disorders
Dyspnea4	18	5
Cough5	15	1
General disorders and administration site conditions
Fatigue6	17	2
Edema7	11	0
Skin and subcutaneous tissue disorders
Rash8	14	0
Injury, poisoning and procedural complications
Infusion-related reactions9	12	0
Metabolism and nutrition disorders
Decreased appetite	11	1

Source: BIZENGRI Prescribing Information
¹ Based on NCI CTCAE v4.03 and MedDRA v26.0
² Includes post-procedural diarrhea
³ Includes back pain, pain in extremity, musculoskeletal chest pain, myalgia, arthralgia, non-cardiac chest pain, bone pain, musculoskeletal stiffness, neck pain, and spinal pain
⁴ Includes dyspnea exertional
⁵ Includes productive cough
⁶ Includes asthenia
⁷ Includes breast edema, peripheral edema, face edema
⁸ Includes eczema, erythema, dermatitis, dermatitis contact, rash maculopapular, and rash erythematous
⁹ Includes chills, IRR, nausea, cough, diarrhea, back pain, body temperature increased, dyspnea, face edema, fatigue, non-cardiac 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
Abbreviations: AE, adverse event; IRR, infusion-related reaction; MedDRA, Medical Dictionary for Regulatory Activities; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; NSCLC, non-small cell lung cancer; PT, preferred term

Table 8. Select Laboratory Abnormalities ≥20% That Worsened From Baseline in Patients With NRG1-Positive NSCLC Who Received BIZENGRI in the eNRGy Study, Safety Population

Laboratory Abnormality	BIZENGRI1
	All Grades %	Grade 3 or 4 %
Hematology
Decreased hemoglobin	35	4.2
Chemistry
Increased alanine aminotransferase	30	3.1
Decreased magnesium	28	4.3
Increased alkaline phosphatase	27	0
Decreased phosphate	26	1.1
Increased gamma-glutamyl transpeptidase	23	5
Increased aspartate aminotransferase	22	3.1
Decreased potassium	21	2.1

Source: BIZENGRI Prescribing Information
¹ The denominator used to calculate the rate varied from 93 to 96 based on the number of patients with a baseline value and at least one post-treatment value.
Abbreviations: NSCLC, non-small cell lung cancer

Table 9. Adverse Reactions (≥10%) in Patients With NRG1-Positive Pancreatic Adenocarcinoma Who Received BIZENGRI in the eNRGy Study, Safety Population

Adverse Reaction1	BIZENGRI, N=39
	All Grades %	Grade 3 or 4 %
Gastrointestinal disorders
Diarrhea	36	5
Nausea	23	5
Vomiting	23	2.6
Abdominal pain	18	5
Constipation	15	0
Abdominal distension	13	0
Stomatitis	10	0
Musculoskeletal and connective tissue disorders
Musculoskeletal pain2	28	2.6
General disorders and administration site conditions
Fatigue3	21	5
Edema4	13	0
Pyrexia	10	0
Infections and infestations
COVID-19	18	0
Injury, poisoning and procedural complications
Infusion-related reactions5	15	0
Vascular disorders
Hemorrhage6	13	5
Psychiatric disorders
Anxiety	10	0
Skin and subcutaneous tissue disorders
Dry skin	10	0

Source: BIZENGRI Prescribing Information
¹ Based on NCI CTCAE v4.03 and MedDRA v26.0
² Includes back pain, pain in extremity, musculoskeletal chest pain, myalgia, arthralgia, non-cardiac chest pain, bone pain, musculoskeletal stiffness, neck pain, and spinal pain
³ Includes asthenia
⁴ Includes peripheral edema, face edema, localized edema, and peripheral swelling
⁵ Includes chills, IRR, nausea, cough, diarrhea, back pain, body temperature increased, dyspnea, face edema, fatigue, non-cardiac chest pain, oropharyngeal discomfort, paresthesia, pyrexia, and vomiting
⁶ Includes epistaxis, hematochezia, hematuria, and hemorrhoidal hemorrhage
Abbreviations: IRR, infusion-related reaction; MedDRA, Medical Dictionary for Regulatory Activities; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events

Table 10. Select Laboratory Abnormalities ≥20% That Worsened From Baseline in Patients With NRG1-Positive Pancreatic Adenocarcinoma Who Received BIZENGRI in the eNRGy Study, Safety Population

Laboratory Abnormality	BIZENGRI1
	All Grades %	Grade 3 or 4 %
Chemistry
Increased alanine aminotransferase	51	5
Increased aspartate aminotransferase	31	5
Increased bilirubin	31	5
Decreased phosphate	31	2.9
Increased alkaline phosphatase	28	8
Decreased sodium	28	10
Decreased albumin	26	0
Decreased potassium	26	2.6
Decreased magnesium	24	2.6
Increased gamma-glutamyl transpeptidase	23	15
Hematology
Decreased platelets	26	10
Decreased hemoglobin	23	10
Decreased leukocytes	21	2.6

Source: BIZENGRI Prescribing Information
¹ The denominator used to calculate the rate varied from 35 to 39, based on the number of patients with a baseline value and at least one post-treatment value.

Were there any differences in side effects among sex, race and age?

NRG1-Positive NSCLC

• Sex: The majority of patients were female. The number of male patients was limited; therefore, differences in the occurrence of side effects among male patients compared to female patients could not be determined.
• Race: The occurrence of side effects was higher in White patients compared to Asian patients. The number of patients of other races was small; therefore, differences in how the drug worked in other races could not be determined.
• Age: The occurrence of side effects was similar in patients younger and older than 65 years of age.

NRG1-Positive Pancreatic Adenocarcinoma

• Sex: The occurrence of side effects was similar in males and females.
• Race: The number of patients of races other than White was small; therefore, differences in side effects among races could not be determined.
• Age: The majority of patients were younger than 65 years of age. The number of patients 65 years of age and older was limited; therefore, differences in the occurrence of side effects among age groups could not be determined.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

Table 11 and Table 12 summarize adverse events that occurred in sex, age, and race subgroups.

Table 11. Side Effects by Subgroup in Patients With NRG1-Positive NSCLC, Safety Population

Demographics	BIZENGRI, N=99
	All Grades n/Ns (%)	Grade 3 or 4 n/Ns (%)
Sex
Female	57/61 (93.4)	22/61 (36.1)
Male	32/38 (84.2)	7/38 (18.4)
Age, years
<65	43/46 (93.5)	14/46 (30.4)
≥65	46/53 (86.8)	15/53 (28.3)
Race
White	35/37 (94.6)	16/37 (43.2)
Asian	44/52 (84.6)	9/52 (17.3)
Other	4/4 (100.0)	1/4 (25.0)

Source: Adapted from FDA Review
Abbreviations: N, number of patients in treatment arm; n, number of patients with adverse event; Ns, total number of patients for each specific subgroup and were assigned to that specific arm; NSCLC, non-small cell lung cancer

Table 12. Side Effects by Subgroup in Patients With NRG1-Positive Pancreatic Adenocarcinoma, Safety Population

Demographics	BIZENGRI, N=39
	All Grades n/Ns (%)	Grade 3 or 4 n/Ns (%)
Sex
Female	18/19 (94.7)	10/19 (52.6)
Male	20/20 (100.0)	10/20 (50.0)
Age, years
<65	30/30 (100.0)	13/30 (43.3)
≥65	8/9 (88.9)	7/9 (77.8)
Race
White	31/32 (96.9)	16/32 (50.0)
Asian	5/5 (100.0)	3/5 (60.0)
Other	1/1 (100.0)	1/1 (100.0)

Source: Adapted from FDA Review
Abbreviations: N, number of patients in treatment arm; n, number of patients with adverse event; Ns, total number of patients for each specific subgroup and were assigned to that specific arm

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments. 
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested. 
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial. 
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo. 
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

PRESCRIBING INFORMATION

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