Drug Trials Snapshots: TEVIMBRA
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 TEVIMBRA 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).
TEVIMBRA (tislelizumab-jsgr)
(Teh-vim’-brah)
BeiGene
Approval date: March 14, 2024
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
TEVIMBRA is a programmed death receptor-1 (PD-1) blocking antibody for the treatment of adults with a type of esophageal cancer called esophageal squamous cell carcinoma (ESCC) that has spread to other parts of the body (metastatic) or cannot be completely removed by surgery (unresectable). It is approved to treat patients who have undergone prior treatment with chemotherapy for their ESCC that did not include a PD-1 blocking antibody.
How is this drug used?
TEVIMBRA is an injection given by a healthcare professional directly into the vein (an intravenous infusion) over 30 to 60 minutes every three weeks.
Who participated in the clinical trials?
The FDA approved TEVIMBRA based on evidence from one clinical trial (RATIONALE-302, NCT03430843) that enrolled 512 patients with previously treated unresectable or metastatic ESCC. Patients did not receive prior treatment with immune checkpoint inhibitors, a type of drugs that are similar to TEVIMBRA. The trial was conducted at 132 medical centers in 11 countries in Asia, Europe, and the United States (only two patients were enrolled in the United States).
How were the trials designed?
The RATIONALE-302 trial enrolled patients with previously treated unresectable or metastatic ESCC that did not receive prior treatment with immune checkpoint inhibitors. Patients received either TEVIMBRA or chemotherapy every three weeks. Treatment continued until progression of disease or development of intolerable side effects. The trial measured the length of time that patients survived while receiving TEVIMBRA compared to chemotherapy.
How were the trials designed?
RATIONALE-302 (NCT03430843) was a multicenter, randomized (1:1), open-label trial in 512 adult patients with unresectable advanced or metastatic ESCC who progressed on or after prior systemic chemotherapy. Patients were enrolled regardless of their tumor PD-L1 expression level. PD-L1 expression was evaluated at a central laboratory using the Ventana PD-L1 (SP263) assay that identified PD-L1 staining on both tumor and tumor associated immune cells. The trial excluded patients who received a prior immune checkpoint inhibitor, had brain or leptomeningeal metastases that were symptomatic or required treatment, active autoimmune disease (a medical condition requiring systemic corticosteroids or immunosuppressants), or apparent tumor invasion of organs adjacent to the esophageal tumor.
Patients were randomized (1:1) to receive either TEVIMBRA 200 mg every three weeks or investigator’s choice of chemotherapy (ICC), all given intravenously: paclitaxel 135 to 175 mg/m2 every three weeks or 80 to 100 mg/m2 weekly; docetaxel 75 mg/m2 every three weeks; or irinotecan 125 mg/m2 on Days 1 and 8 of every three-week cycle. Patients were treated until disease progression assessed by the investigator or unacceptable toxicity.
Randomization was stratified by geographic region (Asia [excluding Japan] versus Japan versus United States/European Union), Eastern Cooperative Oncology Group (ECOG) performance status (0 versus 1), and ICC option. Tumor assessments were conducted every six weeks for the first six months, then every nine weeks until disease progression.
The major efficacy outcome measure was overall survival in the intent-to-treat population. Additional efficacy outcome measures were investigator-assessed progression-free survival, overall response rate, and duration of response per RECIST v1.1.
A total of 512 patients were enrolled and randomized to TEVIMBRA (n=256) or ICC (n=256; irinotecan [46%], paclitaxel [33%], or docetaxel [21%]). Of the 512 patients, 142 (28%) had PD-L1 = 10%, 222 (43%) had PD-L1 <10%, and 148 (29%) had unknown baseline PD-L1 status.
The trial population characteristics were: median age of 62 years (range: 35 to 86), 38% age = 65; 84% male; 19% White and 80% Asian; 95% had metastatic disease. All patients had received at least one prior anti-cancer systemic therapy. Baseline ECOG performance status was 0 (25%) or 1 (75%).
RATIONALE-302 demonstrated a statistically significant improvement in overall survival for patients randomized to TEVIMBRA as compared with ICC.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many males and females were enrolled in the TEVIMBRA clinical trial.
Figure 1. Baseline Demographics by Sex
Source: Adapted from FDA Review
Figure 2 summarizes how many patients by race were enrolled in the TEVIMBRA clinical trial.
Figure 2. Baseline Demographics by Race
Source: Adapted from FDA Review
Figure 3 summarizes how many patients by age were enrolled in the TEVIMBRA clinical trial.
Figure 3. Baseline Demographics by Age
Source: Adapted from FDA Review
Figure 4 summarizes how many patients by ethnicity were enrolled in the TEVIMBRA clinical trial.
Figure 4. Baseline Demographics by Ethnicity
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Demographics Characteristics in the Clinical Trial
| Demographic | TEVIMBRA N=256 |
Chemotherapy N=256 |
Total N=512 |
|---|---|---|---|
| Age, years | |||
| Median (min, max) | 62.0 (40, 86) | 63.0 (35, 81) | 62.0 (35, 86) |
| Age group, years, n (%) | |||
| <65 | 157 (61.3) | 161 (62.9) | 318 (62.1) |
| ≥65 | 99 (38.7) | 95 (37.1) | 194 (37.9) |
| Sex, n (%) | |||
| Female | 39 (15.2) | 41 (16.0) | 80 (15.6) |
| Male | 217 (84.8) | 215 (84.0) | 432 (84.4) |
| Race, n (%) | |||
| Asian | 201 (78.5) | 207 (80.9) | 408 (79.7) |
| White | 53 (20.7) | 44 (17.2) | 97 (18.9) |
| Black or African American | 0 (0.0) | 2 (0.8) | 2 (0.4) |
| Other/Not reported/Unknown | 2 (0.8) | 3 (1.2) | 5 (1.0) |
| Ethnicity, n (%) | |||
| Not Hispanic or Latino | 252 (98.4) | 252 (98.4) | 504 (98.4) |
| Hispanic or Latino | 2 (0.8) | 2 (0.8) | 4 (0.8) |
| Not reported/Unknown | 2 (0.8) | 2 (0.8) | 4 (0.8) |
| Region, n (%) | |||
| North America | 0 (0.0) | 2 (0.8) | 2 (0.3) |
| Europe | 53 (20.7) | 53 (20.7) | 106 (20.7) |
| Asia | 203 (79.2) | 201 (78.5) | 404 (78.9) |
Source: Adapted from FDA Review
What are the benefits of this drug?
In the RATIONALE-302 trial, the median overall survival for patients treated with TEVIMBRA was about 8.6 months compared to 6.3 months for patients treated with chemotherapy.
What are the benefits of this drug (results of trials used to assess efficacy)?
Efficacy results from the clinical trial are summarized in Table 2. The major efficacy outcome was overall survival.
Table 2. Summary of Efficacy
| Overall Survival | TEVIMBRA N=256 |
Chemotherapy N=256 |
|---|---|---|
| Number of patient deaths, n (%) | 197 (77.0) | 213 (83.2) |
| Median overall survival (months) (95% CI) | 8.6 (7.5, 10.4) | 6.3 (5.3, 7.0) |
| Hazard ratiob (95% CI) | 0.70 (0.57, 0.85) | |
| p-valuec | 0.0001 | |
a Estimated using Kaplan-Meier Method
b Based on Cox regression model stratified by ECOG performance status and Investigator's choice of chemotherapy
c One-sided p-value based on log rank test stratified by ECOG performance status and Investigator's choice of chemotherapy.
Abbreviations: CI, confidence interval; ECOG, Eastern Cooperative Oncology Group
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: TEVIMBRA worked similarly in males and females.
- Race: The majority of patients were Asian or White. TEVIMBRA worked similarly in these populations. Due to the small number of patients in other racial subgroups, differences in response among racial groups could not be determined.
- Age: TEVIMBRA 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?
Observations of efficacy based on subgroups of the population studied are provided in Table 3.
Table 3. Total Number of Deaths by Subgroup
| Subgroup | TEVIMBRA N=256 n/Ns (%) |
Chemotherapy N=256 n/Ns (%) |
Hazard Ratio (95% CI) |
|---|---|---|---|
| Age, years | |||
| <65 | 128/157 (81.5) | 133/161 (82.6) | 0.73 (0.57, 0.93) |
| ≥65 | 69/99 (69.6) | 80/95 (84.2) | 0.64 (0.47, 0.89) |
| Sex | |||
| Male | 171/217 (78.8) | 178/215 (82.8) | 0.74 (0.60, 0.92) |
| Female | 26/39 (66.6) | 35/41 (85.3) | 0.47 (0.27, 0.80) |
| Race | |||
| Asian | 162/201 (80.6) | 174/207 (84) | 0.73 (0.59, 0.91) |
| White | 33/53 (62.2) | 34/44 (77.2) | 0.53 (0.32, 0.87) |
Source: Adapted from FDA Review
Abbreviations: CI, confidence interval; 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
What are the possible side effects?
TEVIMBRA may cause serious and potentially deadly immune reactions including inflammation of the lungs (pneumonitis), gut, liver, kidneys, hormonal glands, and skin as well as infusion related reactions. The most common side effects (≥20% of patients) were anemia (low red blood cell count), fatigue, musculoskeletal pain, decreased weight, and cough.
What are the possible side effects (results of trials used to assess safety)?
The possible side effects occurring in ≥10% of patients in the study where TEVIMBRA was used are detailed in Table 4.
Table 4. Adverse Reactions Occurring in ≥10% Patients
| Adverse Reaction | TEVIMBRA, N=255 | Chemotherapy, N=255 | ||
|---|---|---|---|---|
| All Grades % |
Grade 3 to 4 % |
All Grades % |
Grade 3 to 4 % |
|
| Blood disorders | ||||
| Anemia | 31 | 6 | 45 | 11 |
| General disorders | ||||
| Fatigue1 | 28 | 2 | 46 | 6 |
| Fever | 16 | 0.4 | 14 | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Musculoskeletal pain1 | 24 | 1 | 25 | 1 |
| Investigations | ||||
| Weight decreased | 23 | 1 | 19 | 0 |
| Respiratory, thoracic, and mediastinal disorders | ||||
| Cough1 | 22 | 0.4 | 16 | 0.4 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 16 | 0.4 | 35 | 0.4 |
| Infections and infestations | ||||
| Pneumonia1 | 16 | 6 | 12 | 7 |
| Gastrointestinal disorders | ||||
| Constipation | 15 | 0 | 19 | 0.4 |
| Nausea | 14 | 0.4 | 30 | 3 |
| Diarrhea1 | 13 | 1 | 32 | 7 |
| Dysphagia | 11 | 6 | 8 | 3 |
| Abdominal pain1 | 11 | 0.8 | 16 | 2 |
| Vomiting | 11 | 0.8 | 20 | 4 |
| Endocrine disorders | ||||
| Hypothyroidism1 | 13 | 0.4 | 0.8 | 0 |
| Skin and subcutaneous disorders | ||||
| Rash1 | 13 | 0.4 | 6 | 0 |
| Vascular disorders | ||||
| Hemorrhage1 | 12 | 2 | 10 | 3 |
Source: Adapted from TEVIMBRA Prescribing Information
1Represents a composite of multiple related terms
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of side effects was similar in males and females. Females treated with TEVIMBRA experienced more fatigue and diarrhea than males.
- Race: The majority of patients were Asian. White patients treated with TEVIMBRA experienced more fever, decreased appetite, nausea, fatigue, diarrhea, dysphagia, and asthenia than Asian patients.
- Age: The occurrence of side effects was similar in patients younger and older than 65 years of age. Patients 65 years or older experienced more fever and diarrhea than younger patients.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 5. Side Effects (≥20%) by Sex, Safety Population
| Side Effect | TEVIMBRA, N=255 | Chemotherapy, N=240 | ||
|---|---|---|---|---|
| Male N=216 n (%) |
Female N=39 n (%) |
Male N=204 n (%) |
Female N=36 n (%) |
|
| Total | 206 (95.4) | 38 (97.4) | 201 (98.5) | 35 (97.2) |
| Anemia | 68 (31.5) | 10 (25.6) | 94 (46.1) | 13 (36.1) |
| Weight decreased | 52 (24.1) | 7 (17.9) | 39 (19.1) | 6 (16.7) |
| Decreased appetite | 34 (15.7) | 6 (15.4) | 74 (36.3) | 10 (27.8) |
| Constipation | 32 (14.8) | 7 (17.9) | 35 (17.2) | 10 (27.8) |
| Nausea | 28 (13.0) | 8 (20.5) | 58 (28.4) | 14 (38.9) |
| Fatigue | 26 (12.0) | 7 (17.9) | 33 (16.2) | 9 (25.0) |
| Diarrhea | 24 (11.1) | 8 (20.5) | 65 (31.9) | 12 (33.3) |
| Vomiting | 24 (11.1) | 3 (7.7) | 38 (18.6) | 10 (27.8) |
| White blood cell count decreased | 7 (3.2) | 2 (5.1) | 85 (41.7) | 13 (36.1) |
| Neutrophil count decreased | 4 (1.9) | 2 (5.1) | 83 (40.7) | 11 (30.6) |
| Alopecia | 0 (0.0) | 0 (0.0) | 29 (14.2) | 13 (36.1) |
Source: Adapted from FDA Review
Table 6. Side Effects (≥20%) by Race, Safety Population
| Side Effect | TEVIMBRA, N=256 | Chemotherapy, N=240 | ||
|---|---|---|---|---|
| Asian N=201 n (%) |
White N=52 n (%) |
Asian N=194 n (%) |
White N=42 n (%) |
|
| Total | 192 (95.5) | 50 (96.2) | 192 (99.0) | 41 (97.6) |
| Anemia | 62 (30.8) | 15 (28.8) | 91 (46.9) | 15 (35.7) |
| Weight decreased | 56 (27.9) | 3 (5.8) | 40 (20.6) | 5 (11.9) |
| Pyrexia | 30 (14.9) | 11 (21.2) | 28 (14.4) | 6 (14.3) |
| Decreased appetite | 29 (14.4) | 11 (21.2) | 66 (34.0) | 18 (42.9) |
| Nausea | 25 (12.4) | 11 (21.2) | 58 (29.9) | 13 (31.0) |
| Fatigue | 19 (9.5) | 14 (26.9) | 26 (13.4) | 15 (35.7) |
| Diarrhea | 16 (8.0) | 15 (28.8) | 56 (28.9) | 21 (50.0) |
| Dysphagia | 15 (7.5) | 13 (25.0) | 11 (5.7) | 8 (19.0) |
| Asthenia | 10 (5.0) | 16 (30.8) | 24 (12.4) | 11 (26.2) |
| White blood cell count decreased | 9 (4.5) | 0 (0.0) | 97 (50.0) | 1 (2.4) |
| Neutrophil count decreased | 5 (2.5) | 1 (1.9) | 90 (46.4) | 4 (9.5) |
| Neutropenia | 2 (1.0) | 0 (0.0) | 20 (10.3) | 11 (26.2) |
| Alopecia | 0 (0.0) | 0 (0.0) | 32 (16.5) | 9 (21.4) |
Source: Adapted from FDA Review
Table 7. Side Effects (≥20%) by Age, Safety Population
| Side Effect | TEVIMBRA, N=255 | Chemotherapy, N=240 | ||
|---|---|---|---|---|
| <65 Years N=157 n (%) |
≥65 Years N=98 n (%) |
<65 Years N=149 n (%) |
≥65 Years N=91 n (%) |
|
| Total | 154 (98.1) | 90 (91.8) | 146 (98.0) | 90 (98.9) |
| Anemia | 50 (31.8) | 28 (28.6) | 69 (46.3) | 38 (41.8) |
| Weight decreased | 37 (23.6) | 22 (22.4) | 33 (22.1) | 12 (13.2) |
| Decreased appetite | 30 (19.1) | 10 (10.2) | 52 (34.9) | 32 (35.2) |
| Nausea | 24 (15.3) | 12 (12.2) | 47 (31.5) | 25 (27.5) |
| Vomiting | 21 (13.4) | 6 (6.1) | 33 (22.1) | 15 (16.5) |
| Pyrexia | 20 (12.7) | 21 (21.4) | 23 (15.4) | 11 (12.1) |
| Diarrhea | 14 (8.9) | 18 (18.4) | 44 (29.5) | 33 (36.3) |
| White blood cell count decreased | 6 (3.8) | 3 (3.1) | 63 (42.3) | 35 (38.5) |
| Neutrophil count decreased | 5 (3.2) | 1 (1.0) | 57 (38.3) | 37 (40.7) |
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.