Drug Trials Snapshots: IMDELLTRA
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 IMDELLTRA Prescribing Information for all 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).
IMDELLTRA (tarlatamab/dlle)
im-del’-trah
Amgen
Approval date: May 16, 2023
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
IMDELLTRA is a drug approved for the treatment of adult patients with extensive stage small cell lung cancer (ES-SCLC), whose cancer has progressed after prior treatment with chemotherapy that contains platinum.
How is this drug used?
IMDELLTRA is an injection given by healthcare professionals directly into the vein (an intravenous infusion) over one hour every week for the first three doses and then every two weeks after that.
Who participated in the clinical trials?
The FDA approved IMDELLTRA based on evidence from one clinical trial (DeLLphi-301, NCT05060016) of 99 adult patients with relapsed or refractory ES-SCLC who received prior treatment with platinum chemotherapy and one other therapy. The trial was conducted at 56 sites in 14 countries in Europe, Asia, and North America (three patients were enrolled in the United States).
The safety of IMDELLTRA was evaluated in 187 patients from two clinical trials (DeLLphi-301 and DeLLphi-300, NCT03319940); all were patients with relapsed or refractory ES-SCLC who received prior treatment with platinum chemotherapy and one other therapy.
How were the trials designed?
The efficacy of IMDELLTRA was evaluated in one open-label, multicenter, multi-cohort clinical trial (DeLLphi-301). Eligible patients were required to have relapsed or refractory SCLC with disease progression after receiving previous treatment with platinum-based chemotherapy and at least one other line of prior therapy, an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1, and at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The trial excluded patients with symptomatic brain metastases, evidence of interstitial lung disease or noninfectious pneumonitis, and active immunodeficiency.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the clinical trial used to evaluate the efficacy of IMDELLTRA.
Figure 1. Baseline Demographics by Sex, Efficacy Population
Source: Adapted from FDA Review
Figure 2 summarizes the percentage of patients by race enrolled in the clinical trial used to evaluate the efficacy of IMDELLTRA.
Figure 2. Baseline Demographics by Race, Efficacy Population
Source: Adapted from FDA Review
Figure 3 summarizes the percentage of patients by age enrolled in the clinical trial used to evaluate the efficacy of IMDELLTRA.
Figure 3. Baseline Demographics by Age, Efficacy Population
Source: Adapted from FDA Review
Figure 4 summarizes the percentage of patients by ethnicity enrolled in the clinical trial used to evaluate the efficacy of IMDELLTRA.
Figure 4. Baseline Demographics by Ethnicity, Efficacy Population
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics, Efficacy Population
|
Demographic |
IMDELLTRA N=99 |
|
Sex, n (%) |
|
|
Male |
71 (72) |
|
Female |
28 (28) |
|
Age, years |
|
|
Median (min, max) |
64 (35, 82) |
|
Age group, years, n (%) |
|
|
<65 |
51 (52) |
|
≥65 |
48 (48) |
|
≥75 |
10 (10) |
|
Race, n (%) |
|
|
White |
57 (58) |
|
Black/African American |
0 |
|
Asian |
41 (41) |
|
Other |
1 (1) |
|
Ethnicity, n (%) |
|
|
Hispanic or Latino |
1 (1) |
|
Not Hispanic or Latino |
98 (99) |
|
Region, n (%) |
|
|
Europe |
55 (56) |
|
Asia |
41 (41) |
|
North America |
3 (3) |
|
ECOG performance status, n (%) |
|
|
0 |
26 (26) |
|
1 |
73 (74) |
|
Smoking status, n (%) |
|
|
Never |
8 (8) |
|
Current |
18 (18) |
|
Former |
73 (74) |
Source: Adapted from FDA Review
Abbreviations: ECOG, Eastern Cooperative Oncology Group
What are the benefits of this drug?
IMDELLTRA 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 DeLLphi-301, 44% of the 99 patients with relapsed or refractory ES-SCLC experienced complete or partial shrinkage of their tumors; 2 patients had complete shrinkage while 38 patients had partial shrinkage of their tumors. Of the patients who had complete or partial tumor shrinkage, the median duration this lasted was 9.7 months, with 68% of patients having the shrinkage lasting more than 6 months and 40% of patients having tumor shrinkage lasting more than 12 months..
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2. Efficacy Results, Efficacy Population
|
Efficacy Parameter |
IMDELLTRA N=99 |
|
Overall response rate |
|
|
Overall response rate, % (95% CI)a |
40 (31, 51) |
|
Complete response, n (%) |
2 (2) |
|
Partial response, n (%) |
38 (38) |
|
Duration of responsea |
|
|
Medianb, months (min, max) |
9.7 (2.7, 20.7+) |
|
Duration ≥6 monthsc, % |
68 |
|
Duration ≥12 monthsc, % |
40 |
Source: IMDELLTRA Prescribing Information
a Assessed by Blinded Independent Central Review
bMedian based on Kaplan-Meier estimate.
cBased on observed duration of response.
Abbreviations: CI, confidence interval
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: IMDELLTRA worked similarly in males and females.
- Race: IMDELLTRA worked similarly in White and Asian patients. Differences among other races could not be determined because of the small number of patients of other races.
- Age: There were insufficient number of patients to determine whether IMDELLTRA worked similarly in patients younger and older than 65 years of age.
What are the possible side effects?
IMDELLTRA can cause serious side effects including cytokine release syndrome (CRS), neurologic toxicity including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), cytopenia, infections, hepatoxicity, hypersensitivity, and embryo-fetal toxicity.
The most common side effects include CRS, fatigue, fevers, bad or metallic taste in mouth, and decreased appetite.
What are the possible side effects (results of trials used to assess safety)?
The most common adverse reactions were CRS, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia, and nausea. The most common serious laboratory abnormalities were decreased lymphocytes, decreased sodium, increased uric acid, decreased total neutrophils, decreased hemoglobin, increased activated partial thromboplastin time, decreased potassium, increased aspartate aminotransferase, decreased white blood cells, decreased platelets, and increased alanine aminotransferase.
Table 3. Adverse Reactions (≥15%) in Patients With ES-SCLC Who Received IMDELLTRA, Safety Population
| Adverse Reactiona |
IMDELLTRA, N=187 |
|
|||
|
Any Grade % |
Grade 3 or 4 % |
||||
|
Immune system disorders |
|||||
|
Cytokine release syndromeb |
55 |
1.6 |
|||
|
General disorders and administration site conditions |
|||||
|
Fatiguec |
51 |
10 |
|||
|
Pyrexia |
36 |
0 |
|||
|
Nervous system disorders |
|||||
|
Dysgeusia |
36 |
0 |
|||
|
Metabolism and nutrition disorders |
|||||
|
Decreased appetite |
34 |
2.7 |
|||
|
Nausea |
22 |
1.6 |
|||
|
Gastrointestinal disorders |
|||||
|
Constipation |
30 |
0.5 |
|||
|
Musculoskeletal and connective tissue disorders |
|||||
|
Musculoskeletal paind |
30 |
1.1 |
|||
|
Blood and lymphatic system disorders |
|||||
|
Anemia |
27 |
6 |
|||
|
Respiratory, thoracic and mediastinal disorders |
|||||
|
Dyspneae |
17 |
2.1 |
|||
|
Cough |
17 |
0 |
|||
Source: IMDELLTRA Prescribing Information
a Graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and version 5.0.
b Based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019.
c Includes fatigue and asthenia.
d Includes myalgia, arthralgia, back pain, pain in extremity, neck pain, musculoskeletal chest pain, non-cardiac chest pain, and bone pain.
e Includes dyspnea and exertional dyspnea.
Abbreviations: ES-SCLC, extensive stage small cell lung cancer
Table 4. Laboratory Abnormalities (>20%) That Worsened From Baseline in Patients With ES-SCLC, Safety Population
| Laboratory Abnormality |
IMDELLTRAa |
|
|
All Grades % |
Grade 3 or 4 % |
|
|
Hematology |
||
|
Decreased lymphocytes |
84 |
57 |
|
Decreased hemoglobin |
58 |
5 |
|
Decreased white blood cells |
44 |
3.8 |
|
Decreased platelets |
33 |
3.2 |
|
Decreased neutrophilsb |
12 |
6 |
|
Chemistry |
||
|
Decreased sodium |
68 |
16 |
|
Decreased potassium |
50 |
5 |
|
Increased aspartate amino transferase |
44 |
3.2 |
|
Increased alanine aminotransferase |
42 |
2.1 |
|
Decreased magnesium |
33 |
1.6 |
|
Increased creatinine |
29 |
0.5 |
|
Increased sodium |
26 |
0.0 |
|
Increased alkaline phosphate |
22 |
0.0 |
Source: IMDELLTRA Prescribing Information
a The denominator used to calculate the rate varied from 41 to 187 based on the number of patients with a baseline value and at least one post-treatment value.
b All Grade lab abnormalities occurring at a frequency less than 20% included decreased neutrophils. Abbreviations: ES-SCLC, extensive stage small cell lung cancer
Were there any differences in side effects among sex, race, and age?
- Sex: The occurrence of side effects was similar in males and females.
- Race: The occurrence of side effects was similar in White and Asian patients. Side effects in other races could not be determined because of the small number of patients of other races.
- Age: The occurrence of side effects was similar in patients older than 65 years of age and younger patients.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 5. Adverse Events by Sex, Safety Population
|
Adverse Event |
IMDELLTRA, N=187 |
|
|
Male N=121 n (%) |
Female N=66 n (%) |
|
|
All treatment-emergent adverse events |
121 (100) |
65 (99) |
|
Serious adverse events |
63 (52) |
41 (62) |
|
Leading to dose interruption and/or reduction |
36 (30) |
21 (32) |
|
Leading to discontinuation |
7 (6) |
6 (9) |
Source: Adapted from FDA Review
Table 6. Adverse Events by Age Group, Safety Population
| Adverse Event |
IMDELLTRA, N=187 |
||
|
<65 Years N=86 n (%) |
≥65 Years N=101 n (%) |
||
|
All treatment-emergent adverse events |
86 (100) |
100 (99) |
|
|
Serious adverse events |
47 (55) |
57 (56) |
|
|
Leading to dose interruption and/or reduction |
26 (30) |
31 (31) |
|
|
Leading to discontinuation |
4 (5) |
9 (9) |
|
Source: Adapted from FDA Review
Table 7. Adverse Events by Race, Safety Population
|
Adverse Event |
IMDELLTRA, N=187 |
|||
|
Black or African American N=4 n (%) |
Other N=5 n (%) |
Asian N=48 n (%) |
White N=130 n (%) |
|
|
All treatment-emergent adverse events |
4 (100) |
5 (100) |
48 (100) |
129 (99) |
|
Serious adverse events |
2 (50) |
4 (80) |
28 (58) |
70 (54) |
|
Leading to dose interruption and/or reduction |
1 (25) |
0 (0) |
12 (25) |
53 (51) |
|
Leading to discontinuation |
0 (0) |
0 (0) |
2 (4.2) |
8 (8) |
Source: Adapted from FDA Review
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.
