Drug Trials Snapshots: COLUMVI

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 COLUMVI 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).

COLUMVI (glofitamab-gxbm)
ko-loom-vee
Genentech, Inc.
Original Approval date: June 15, 2023

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DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

COLUMVI is a drug used to treat adult patients with certain types of diffuse large B-cell lymphoma (DLBCL) or large B-cell lymphoma (LBCL) who have received at least two prior treatments that did not work or are no longer working.

LBCL is a type of blood cancer.

How is this drug used?

COLUMVI is given through a vein, as an intravenous (IV) infusion, that is taken for up to 12 treatment cycles. Note that one week before starting the first treatment cycle of COLUMVI, patients will receive a separate drug, obinutuzumab, as an IV infusion. The first treatment cycle includes two smaller doses of COLUMVI infusions, which are given on two separate days, one week apart. The remaining 11 treatment cycles include one COLUMVI infusion every three weeks.

Who participated in the clinical trials?

The FDA approved COLUMVI based on evidence from a clinical trial NP30179 (NCT03075696) of 145 patients with LBCL who received at least one dose of COLUMVI. The efficacy of COLUMVI was assessed in 132 patients with de novo DLBCL, not otherwise specified (NOS) (80%) or LBCL arising from follicular lymphoma (20%), who have received at least two prior lines of therapy and who received at least one dose of COLUMVI. The trial was conducted at 32 sites in 13 of countries in Australia, Belgium, Canada, Czech Republic, Denmark, Spain, Finland, France, Italy, New Zealand, Poland, Taiwan, and the United States.

How were the trials designed?

There was one trial that provided data for COLUMVI’s approval.

The benefit and side effects of COLUMVI were evaluated in Study NP30179 (NCT03075696), a clinical trial including 145 adult patients with de novo DLBCL, NOS (80%) or LBCL arising from follicular lymphoma (20%) who had received at least two prior lines of therapy that did not work or were no longer working. All patients received COLUMVI until the disease progressed or the side effects became too toxic.

The benefit of COLUMVI was evaluated by measuring how many patients had complete or partial tumor shrinkage (overall response) and by how long that response lasted (duration of response).

How were the trials designed?

The efficacy and safety of COLUMVI were evaluated in a multicenter, open-label trial of patients with LBCL who had received at least two prior therapies that did not work or were no longer working.

Patients received pretreatment with a single dose of obinutuzumab on Day 1 of Cycle 1 (seven days prior to the start of COLUMVI). Following premedication, COLUMVI was administered by IV infusion according to the step-up dosing schedule with 2.5 mg on Day 8 of Cycle 1, and 10 mg on Day 15 of Cycle 1. Patients received the 30 mg COLUMVI dose by IV infusion on Day 1 of subsequent cycles for a maximum of 12 cycles (including step-up dosing). Each cycle was 21 days. Patients were hospitalized during and for 24 hours following completion of at least the first step-up dose.

The main efficacy endpoints for COLUMVI were the response rates (including overall response rate (ORR) and complete response (CR)) and duration of response (DOR), which were assessed by a blinded Independent Review Committee who determined whether and when the tumor(s) shrunk completely or partially.

See COLUMVI Prescribing Information Section 14 (Clinical Data) for more information.

DEMOGRAPHICS SNAPSHOT

Figure 1 summarizes the percentage of male and female patients in the clinical trial used to evaluate the side effects of COLUMVI.

Figure 1. Baseline Demographics by Sex (Safety Population, N=145)

Source: Adapted from FDA Review

Figure 2 summarizes the percentage of patients by race in the clinical trial used to evaluate the side effects of COLUMVI.

Figure 2. Baseline Demographics by Race (Safety Population, N=145)

Source: Adapted from FDA Review
* Note that race information was not part of the standard information collected in the local medical records of all participating countries (i.e., France), thus this data could not always be reported.

Figure 3 summarizes the percentage of patients by age group in the clinical trial used to evaluate the side effects of COLUMVI.

Figure 3. Baseline Demographics by Age (Safety Population, N=145)

Source: Adapted from FDA Review

Figure 4 summarizes the percentage of patients by ethnicity in the clinical trial used to evaluate the side effects of COLUMVI.

Figure 4. Baseline Demographics by Ethnicity (Safety Population, N=145)

Adapted from FDA Review
* Note that ethnicity information was not part of the standard information collected in the local medical records of all participating countries (i.e., France), thus this data could not always be reported.

Who participated in the trials?

Table 1 and Table 2 summarizes the safety and efficacy population demographics of patients in the clinical trial.

Table 1. Demographics of Patients in the Clinical Trial (Safety Population)

Demographic Parameter	COLUMVI N=145 n (%)
Sex
Male	95 (65.5)
Female	50 (34.5)
Race
White	112 (77.2)
Black or African American	2 (1.4)
Asian	7 (4.8)
Unknown	24 (16.6)
Age, years
<65	66 (45.5)
≥65	79 (54.5)

Source: Adapted from FDA Review

Table 2. Demographics of Patients in the Clinical Trial (Efficacy Population)

Subgroup	COLUMVI N=132 n (%)
Sex
Male	85 (64.4)
Female	47 (35.6)
Race
White	102 (77.3)
Black or African American	1 (0.8)
Asian	6 (4.5)
Unknown	23 (17.4)
Age, years
<65	58 (43.9)
≥65	74 (56.1)

Source: Adapted from FDA Review

What are the benefits of this drug?

In a clinical trial with 132 patients with de novo DLBCL, NOS (DLBCL as a first presentation of the lymphoma) or LBCL arising from follicular lymphoma (20%), who had received at least two prior lines of therapy, 56% of patients had a complete or partial remission (shrinkage of their tumors), of which 43% had complete remission.

COLUMVI 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.

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

The main efficacy endpoints for COLUMVI were the response rates (including ORR and CR) and DOR, which were assessed by a blinded Independent Review Committee who determined whether and when the tumor(s) shrunk completely or partially.

Table 3 summarizes efficacy results in adult patients with de novo DLBCL, NOS or LBCL arising from follicular lymphoma who have received at least two prior lines of therapy and were treated with at least one dose of COLUMVI in the clinical trial (efficacy population).

Table 3. Efficacy Results in Patients With Relapsed or Refractory DLBCL, NOS or LBCL Arising From Follicular Lymphoma

Outcome per IRC	COLUMVI N=132
Overall response rate, n (%)	74 (56)
95% CI	47, 65
Complete response, n (%)a	57 (43)
Partial response, n (%)	17 (13)
Duration of response	N=74
Median, months (95% CI)b	18.4 (11.4, NE)
9-month estimate, % (95% CI)b	68.5 (56.7, 80.3)

Source: Adapted from COLUMVI Prescribing Information
^a From date of first response until disease progression or death due to any cause.
^b Kaplan-Meier estimate
Abbreviations: CI, confidence interval; DLBCL, diffuse large B-cell lymphoma; IRC, independent review committee; LBCL, large B-cell lymphoma; NE, not estimated; NOS, not otherwise specified

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

• Sex: COLUMVI worked similarly in males and females.
• Race: Most of the patients in the clinical trial were White. Differences in how well COLUMVI worked among other races could not be determined because of the small number of patients in other races who took part in the clinical trial.
• Age: COLUMVI worked similarly in patients younger and older than 65 years of age.

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

Table 4 summarizes efficacy results by sex, race, and age. Because of the small sample sizes, these exploratory analyses should be interpreted with caution.

Table 4. Analysis of ORR by Sex, Race, and Age

Subgroup	ORR N=132 n/Ns (%)
Sex
Male	40/85 (47)
Female	34/47 (72)
Race
White	57/102 (56)
Black or African American	1/1 (100)
Asian	5/6(83)
Unknown	11/23 (48)
Age, years
<65	32/58 (55)
≥65	42/74 (57)

Source: Adapted from FDA Review
Abbreviations: N, number of patients in treatment arm; n, number of patients meeting criteria; Ns, total number of patients for each specific subgroup and were assigned to that specific arm; ORR, overall response rate

What are the possible side effects?

COLUMVI may cause serious side effects including an acute systemic inflammatory syndrome called cytokine release syndrome (which presents as fever, nausea, headache, rash, rapid heartbeat, low blood pressure, low oxygen levels, and trouble breathing), neurologic problems, serious infections, low blood cell counts , and growth in your tumor or worsening of tumor‐related problems (tumor flare).

The most common side effects of COLUMVI are cytokine release syndrome, muscle and bone pain, rash, and tiredness.

Please refer to the COLUMVI Medication Guide for more details.

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

Table 5 summarizes adverse reactions in adult patients with LBCL who were treated with at least one dose of COLUMVI in the clinical trial (safety population).

Table 5. Select Adverse Reactions (≥10%) in Patients With Relapsed or Refractory LBCL

Adverse Reactions	COLUMVI N=145
	All Grades %	Grade 3 or 4 %
Immune system disorders
Cytokine release syndrome	70	4.1
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	21	2.1
General disorders
Fatigue	20	1.4
Pyrexia	16	0
Edema	10	0
Skin and subcutaneous tissue disorders
Rash	20	1.4
Gastrointestinal disorders
Constipation	14	0
Diarrhea	14	0
Nausea	10	0
Abdominal pain	10	0
Neoplasms
Tumor flare	12	2.8
Neurologic disorders
Headache	10	0

Source: COLUMVI Prescribing Information

Clinically relevant adverse reactions occurring in <10% of patients who received COLUMVI included infusion-related reaction, peripheral neuropathy, pneumonia, mental status changes, vomiting, tumor lysis syndrome, febrile neutropenia, upper respiratory tract infection, sepsis, herpes zoster infection, gastrointestinal hemorrhage, tremor, and myelitis. Table 6 summarizes laboratory abnormalities in the clinical trial.

Table 6. Select Laboratory Abnormalities (≥20%) That Worsened From Baseline in Patients With Relapsed or Refractory LBCL

Laboratory Abnormality	COLUMVIa
	All Grades %	Grade 3 or 4 %
Hematology
Lymphocytes decreased	90	83
Hemoglobin decreased	72	8
Neutrophils decreased	56	26b
Platelets decreased	56	8
Chemistry
Fibrinogen decreased	84	21
Phosphate decreased	69	28
Sodium decreased	49	7
Calcium decreased	48	2.1
Gamma-glutamyl transferase increased	33	9
Potassium decreased	32	6
Uric acid increased	23	23

Source: COLUMVI Prescribing Information
^a The denominator used to calculate the rate varied from 137 to 145 based on the number of patients with a baseline value and at least one post-treatment value.
^b Grade 4 neutrophil decrease occurred in 9% of patients.

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

• Sex: The occurrence of side effects was similar in males and females.
• Race: Most of the patients in the clinical trial were White. Differences in side effects experienced among races could not be determined because of the small number of patients in other races who took part in the clinical trial.
• Age: There was a higher rate of fatal events, primarily from COVID-19, in patients 65 years of age or older compared to younger patients. The occurrence of side effects was otherwise similar in patients younger and older than 65 years of age.

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

Table 7 summarizes some of the common adverse reactions by sex and age subgroups. The analyses by race were not conducted because of the limited number of patients in other races compared to White patients.

Table 7. Overview of Adverse Events by Demographic Subgroup, (Safety Population, N=145), Trial np30179

Characteristic	Total N=145	All Grades N=145 n/Ns (%)	Grades 3 to 4 Total N=145 n/Ns (%)
Sex
Female	50 (34.5)	49/50 (98.0)	30/50 (60.0)
Male	95 (65.5)	94/95 (98.9)	62/95 (65.3)
Race
Asian	7 (4.8)	7/7 (100)	4/7 (57.1)
Black or African American	2 (1.4)	2/2 (100)	1/2 (50.0)
Unknown	24 (16.6)	24/24 (100)	20/24 (83.3)
White	112 (77.2)	110/112 (98.2)	67/112 (59.8)
Age group, years
<65 years	66 (45.5)	65/66 (98.5)	43/66 (65.2)
≥65 years	79 (54.5)	78/79 (98.7)	49/79 (62.0)
Ethnicity
Hispanic or Latino	8 (5.5)	8/8 (100)	5/8 (62.5)
Not Hispanic or Latino	114 (78.6)	112/114 (98.2)	70/114 (61.4)
Not reported	19 (13.1)	19/19 (100)	13/19 (68.4)
Unknown	4 (2.8)	4/4 (100)	4/4 (100)

Source: FDA reviewer’s analysis
Abbreviation: N, number of patients in the safety population; n, number of patients with given characteristic; Ns, total number of patients in each category.

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 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.

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