Drug Trials Snapshots: PENPULIMAB-KCQX
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 PENPULIMAB-KCQX 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).
PENPULIMAB-KCQX injection, for intravenous use
pen-pul-i-mab-kcqx
Akeso Biopharma Co.
Approval date: April 23, 2025
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
PENPULIMAB-KCQX is a programmed death receptor-1 (PD-1)–blocking antibody and is available by prescription. PENPULIMAB-KCQX is used with cisplatin or carboplatin and gemcitabine to treat adult patients with metastatic or recurrent, locally advanced non-keratinizing nasopharyngeal cancer (NPC). PENPULIMAB-KCQX is also used as a single agent for adult patients with recurrent metastatic non-keratinizing NPC with disease progression on or after a platinum-containing chemotherapy and at least one other prior line of therapy.
How is this drug used?
PENPULIMAB-KCQX is an injection given by a healthcare professional directly into the vein through an intravenous (IV) line over 60 minutes. PENPULIMAB-KCQX 200 mg is administered in combination with cisplatin 80 mg/m2 or carboplatin AUC 5 and gemcitabine 1000 mg/m2 every three weeks for six doses, then only PENPULIMAB-KCQX every three weeks. PENPULIMAB-KCQX is administered as a single agent 200 mg every two weeks for up to 24 months.
Who participated in the clinical trials?
The FDA approved PENPULIMAB-KCQX based on evidence from two clinical trials (AK105-304/NCT04974398 and AK105-202/NCT03866967) in adult patients with NPC.
AK105-304 enrolled 291 patients with metastatic or recurrent, locally advanced NPC who had not received previous systemic chemotherapy for recurrent or metastatic disease. The trial was conducted at 46 clinical trial sites from largely from China (36), the United States (1), Canada (2), and Brazil (7). AK105-202 enrolled 125 patients with disease progression of metastatic non-keratinizing NPC who had received prior platinum-based chemotherapy and at least one other line of therapy. The trial was conducted entirely from clinical trial sites in China.
Both the AK105-304 and AK105-202 clinical trial results were used to assess the efficacy and safety of PENPULIMAB-KCQX in combination with cisplatin and gemcitabine or PENPULIMAB-KCQX as a single agent in adult patients with NPC.
How were the trials designed?
Trial AK105-304
AK105-304 was a multicenter, double-blind, randomized (1:1) trial of patients with metastatic or recurrent, locally advanced NPC who had not received previous systemic chemotherapy for recurrent or metastatic disease who received either PENPULIMAB-KCQX with cisplatin and gemcitabine every three weeks for six doses then PENPULIMAB-KCQX every three weeks, or placebo with cisplatin and gemcitabine every three weeks for six doses then placebo every three weeks.
The trial included a total of 291 patients with recurrent or metastatic NPC. Eligible patients were required to have recurrent NPC with local-regional recurrence and/or distant metastasis occurring ≥6 months after completion of curative intent treatment or to have primary metastatic NPC not suitable for local therapy at the time of diagnosis. Patients with autoimmune disease, other than stable hypothyroidism or type I diabetes, and patients who required systemic immunosuppression were ineligible.
Patients were randomized (1:1) to receive either:
- PENPULIMAB-KCQX in combination with either cisplatin or carboplatin and gemcitabine every three weeks for up to six cycles, followed by single-agent PENPULIMAB-KCQX every three weeks until disease progression or unacceptable toxicity or a maximum of 24 months.
- Placebo in combination with either cisplatin or carboplatin and gemcitabine every three weeks for up to six cycles, followed by single-agent placebo every three weeks until disease progression or unacceptable toxicity or a maximum of 24 months. All study medications were administered intravenously.
Randomization was stratified by stage of disease (primary metastatic versus recurrent), Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (0 versus 1), and liver metastasis (present versus absent). Patients randomized to placebo were eligible to receive open-label single-agent PENPULIMAB-KCQX (200 mg every three weeks) after radiographic disease progression confirmed by blinded independent central review (BICR).
Tumor assessments were performed every six weeks for the first 12 months and every nine weeks thereafter. The major efficacy outcome measure was BICR-assessed progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The key secondary efficacy outcome measure was overall survival (OS).
The trial population characteristics were: median age of 51 years (range: 23 to 75); 82% male; 98% Asian; 2.1% White; 1.4% Hispanic or Latino; and 36% ECOG PS of 0. At study entry, 80% of patients had metastatic disease. Histological subtypes of NPC included 96% non-keratinizing, 0.7% keratinizing squamous cell carcinoma, and 3.4% did not have the subtype identified. In total, 98% received cisplatin and 2.4% received carboplatin.
The trial demonstrated statistically significant improvements in BICR-assessed PFS for patients randomized to PENPULIMAB-KCQX in combination with either cisplatin or carboplatin and gemcitabine compared to placebo with either cisplatin or carboplatin and gemcitabine. No significant difference in OS was measured.
Trial AK105-202
The efficacy of single-agent PENPULIMAB-KCQX was evaluated in Trial AK105-202, an open-label, multicenter, single-arm trial conducted in a single country. The trial included a total of 125 patients with unresectable or metastatic non-keratinizing nasopharyngeal carcinoma (NPC) and who had disease progression after platinum-based chemotherapy and at least one other line of therapy. Patients with a history of autoimmune disease or a medical condition that required immunosuppression were ineligible.
Patients received single-agent PENPULIMAB-KCQX 200 mg intravenously every two weeks until disease progression or unacceptable toxicity or a maximum of 24 months. Tumor assessments were performed every 8 weeks in the first year and every 12 weeks thereafter. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR) according to RECIST v1.1 as assessed by an independent radiology review committee (IRRC).
The median age was 50 years (range: 21 to 66 years); 76% were male; 100% were Asian; none were Hispanic or Latino; and ECOG PS was 0 (31%) or 1 (69%). In total, 10% of patients had tumors with PD-L1 Tumor Proportion Score (TPS) <1%; 50% of patients had tumors with PD-L1 TPS 1% to 49%; 37% of patients had tumors with PD-L1 TPS ≥50%; and 2.4% of patients had tumors with missing PD-L1 expression levels. In the study, 63% of patients had received two prior lines of chemotherapy, and 37% of patients had received three or more prior lines of chemotherapy. A total of 92% of patients had received prior radiotherapy.
DEMOGRAPHICS SNAPSHOT
Trial AK105-304
Figure 1 summarizes how many male and female patients were enrolled in Trial AK105-304 used to evaluate the efficacy of PENPULIMAB-KCQX.
Figure 1. Baseline Demographics by Sex, Trial AK105-304
Source: Adapted from FDA Assessment Aid
Figure 2 summarizes how many patients by race were enrolled in Trial AK105-304 used to evaluate the efficacy of PENPULIMAB-KCQX.
Figure 2. Baseline Demographics by Race, Trial AK105-304
Source: Adapted from FDA Assessment Aid
Figure 3 summarizes how many patients by age were enrolled in Trial AK105-304 used to evaluate the efficacy of PENPULIMAB-KCQX.
Figure 3. Baseline Demographics by Age, Trial AK105-304
Source: Adapted from FDA Assessment Aid
Figure 4 summarizes how many patients by ethnicity were enrolled in Trial AK105-304 used to evaluate the efficacy of PENPULIMAB-KCQX.
Figure 4. Baseline Demographics by Ethnicity, Trial AK105-304
Source: Adapted from FDA Assessment Aid
Trial AK105-202
Figure 5 summarizes how many male and female patients were enrolled in Trial AK105-202 used to evaluate the efficacy of PENPULIMAB-KCQX.
Figure 5. Baseline Demographics by Sex, Trial AK105-202
Adapted from FDA Assessment Aid
Figure 6 summarizes how many patients by race were enrolled in Trial AK105-202 used to evaluate the efficacy of PENPULIMAB-KCQX.
Figure 6. Baseline Demographics by Race, Trial AK105-202
Adapted from FDA Assessment Aid
Figure 7 summarizes how many patients by age were enrolled in Trial AK105-202 used to evaluate the efficacy of PENPULIMAB-KCQX.
Figure 7. Baseline Demographics by Age, Trial AK105-202
Adapted from FDA Assessment Aid
Figure 8 summarizes how many patients by ethnicity were enrolled in Trial AK105-202 used to evaluate the efficacy of PENPULIMAB-KCQX.
Figure 8. Baseline Demographics by Ethnicity, Trial AK105-202
Adapted from FDA Assessment Aid
Who participated in the trials?
Table 1. Baseline Demographics by Age, Race, Sex, and Ethnicity, Trial AK105-304
| Subgroup | PENPULIMAB-KCQX + | Placebo + | Total |
|---|---|---|---|
| Sex |
|
|
|
| Male | 120 | 119 | 239 |
| Female | 24 | 28 | 52 |
| Age, years |
|
|
|
<65
| 130 | 142 | 272 |
| ≥65 | 14 | 5 | 19 |
| Race |
|
|
|
| Asian | 140 | 144 | 284 |
| White | 4 | 2 | 6 |
| Other | 0 | 1 | 1 |
| Ethnicity |
|
|
|
| Hispanic or Latino | 2 | 2 | 4 |
| Not Hispanic or Latino | 142 | 145 | 287 |
Source: Adapted from FDA Assessment Aid
Abbreviations: Carb, carboplatin AUC 5; Cis, cisplatin; Gem, gemcitabine
Table 2. Baseline Demographics by Age, Race, Sex, and Ethnicity, Trial AK105-202
| Subgroup | PENPULIMAB-KCQX |
|---|---|
| Sex |
|
| Male | 99 |
| Female | 31 |
| Age, years |
|
| 18 to 65 | 128 |
| >65 | 2 |
| Race |
|
| Asian | 130 |
| Ethnicity |
|
| Not Hispanic or Latino | 130 |
Source: Adapted from FDA Assessment Aid
What are the benefits of this drug?
PENPULIMAB-KCQX demonstrated statistically significant improvements in BICR-assessed PFS for patients randomized to PENPULIMAB-KCQX in combination with either cisplatin or carboplatin and gemcitabine compared to placebo with either cisplatin or carboplatin and gemcitabine. Overall survival was not significantly different.
PENPULIMAB-KCQX as a single agent demonstrated anti-tumor activity and duration of response.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 3. Efficacy Results, Trial AK105-304, Intention-to-Treat Population
| BICR-Assessed PFS1 | PENPULIMAB-KCQX + | Placebo + |
|---|---|---|
| Number of events, n (%) | 80 (56) | 109 (74) |
| Median, months (95% CI) | 9.6 (7.1, 12.5) | 7.0 (6.9, 7.3) |
| Hazard ratio (95% CI)2 | 0.45 (0.33, 0.62) | |
| p-value3 | <0.0001 | |
Source: PENPULIMAB-KCQX Prescribing Information
1 PFS results are based on the data cutoff of April 29, 2024.
2 Based on a stratified Cox proportional hazard model.
3 T Two-sided p-value, based on the stratified log-rank test, as compared with an alpha boundary of 0.030.
Abbreviations: Cis, cisplatin; Gem, gemcitabine; PFS, progression-free survival
Table 4. Efficacy Results, Trial AK105-202, Intention-to-Treat Population
| Endpoint | PENPULIMAB-KCQX |
|---|---|
| IRRC-assessed ORR, % (95% CI) | 28 (20, 37) |
| Complete response rate, % | 0.8 |
| Partial response rate, % | 27 |
| BICR-assessed DOR | N=35 |
| Median1, months (95% CI) | NR (9.2, NE) |
| Patients with DOR ≥12 months2, % | 46 |
Source: PENPULIMAB-KCQX Prescribing Information
1 Estimated using Kaplan-Meier method
2Based on observed DOR data
Abbreviations: BICR, blinded independent central review; CI, confidence interval; DOR, duration of response; IRRC, independent radiology review committee; NE, not estimable; NR, not reached; ORR, objective response rate
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
Trial AK105-304:
- Sex: There was no significant difference in the risk of progression or death between males and females.
- Race: Because the vast majority of patients were Asian, differences between races in how PENPULIMAB-KCQX with cisplatin and gemcitabine worked could not be determined.
- Age: There was no significant difference in the risk of progression or death between patients older or younger than 65 years of age.
Trial AK105-202:
- Sex: PENPULIMAB-KCQX worked similarly in males and females.
- Race: All patients were Asian, therefore, differences between races in how PENPULIMAB-KCQX worked as a single agent could not be determined.
- Age: Almost all participants were younger than 65 years old; therefore, differences between the age groups (18 to 65 and > 65) in how well PENPULIMAB-KCQX worked 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. Efficacy Results by Sex and Age, Trial AK105-304, Intention-to-Treat Population
| Subgroup | PENPULIMAB-KCQX + | Placebo + | |
|---|---|---|---|
PFS Events/n (%) | Hazard Ratio (95% CI) | PFS Events/n (%) | |
| Age, years |
|
|
|
| 18 to 50 | 39/66 (59) | 0.59 (0.39, 0.9) | 53/70 (76) |
| >50 | 41/78 (53) | 0.46 (0.3, 0.71) | 56/70 (80) |
| Sex |
|
|
|
| Male | 67/119 (56) | 0.57 (0.41, 0.79) | 86/199 (72) |
| Female | 13/25 (52) | 0.44 (0.22, 0.89) | 23/28 (82) |
Source: Adapted from FDA Assessment Aid
Abbreviations: CI, confidence interval; Cis, cisplatin; Gem, gemcitabine; PFS, progression-free survival
Table 6. Efficacy Results by Sex and Age, Trial AK105-202, Efficacy Population
| Subgroup | Responders/n | ORR, % (95% CI) |
|---|---|---|
| Age, years |
|
|
| <65 | 33/109 | 30 (22, 40) |
| ≥65 | 0/2 | 0 (0, 84) |
| Sex |
|
|
| Male | 26/84 | 31 (21, 42) |
| Female | 7/27 | 26 (11, 46) |
Source: Adapted from FDA Assessment Aid
Abbreviations: CI, confidence interval; ORR, objective response rate
What are the possible side effects?
PENPULIMAB-KCQX in combination with either cisplatin or carboplatin and gemcitabine: The most common adverse reactions (≥20%) were nausea, vomiting, hypothyroidism, constipation, decreased appetite, decreased weight, cough, COVID-19 infection, fatigue, rash, and pyrexia.
PENPULIMAB-KCQX as a single agent: The most common adverse reactions (≥20%) were anemia and hypothyroidism.
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 PENPULIMAB-KCQX in combination with cisplatin and gemcitabine and PENPULIMAB-KCQX as a single agent were administered in the clinical trials are detailed below.
Table 7. Safety Results - Adverse Reactions (≥10%), Trial AK105-304, Safety Population
| Adverse Reaction | PENPULIMAB-KCQX + | Placebo + | ||
|---|---|---|---|---|
| All Grades1 % | Grade 3 or 41 % | All Grades1 % | Grade 3 or 41 % | |
| Gastrointestinal disorders | ||||
| Nausea | 58 | 2.1 | 64 | 0 |
| Vomiting2 | 55 | 1.4 | 54 | 1.4 |
| Constipation | 41 | 0 | 44 | 0 |
| Abdominal distension | 12 | 0 | 6 | 0 |
| Endocrine disorders | ||||
| Hypothyroidism3 | 45 | 0 | 27 | 0 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 36 | 0 | 39 | 0 |
| Investigations | ||||
| Weight decreased | 26 | 1.4 | 16 | 0 |
| Respiratory, thoracic, and mediastinal disorders | ||||
| Cough4 | 25 | 0/td> | 16 | 0 |
| Infections and infestations | ||||
| COVID-19 | 25 | 0 | 17 | 0.7 |
| General disorders and administration site conditions | ||||
| Fatigue5 | 25 | 1.4 | 22 | 0 |
| Pyrexia | 21 | 0 | 20 | 0.7 |
| Malaise | 10 | 0 | 8 | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Rash6 | 24 | 1.4 | 20 | 0 |
| Pruritus | 11 | 0 | 11 | 0 |
| Nervous system disorders | ||||
| Headache | 15 | 0.7 | 10 | 0.7 |
| Dizziness7 | 14 | 0 | 15 | 0.7 |
| Renal and urinary disorders | ||||
| Proteinuria | 14 | 0 | 13 | 0 |
| Acute kidney injury8 | 13 | 1.4 | 4.9 | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Musculoskeletal pain9 | 14 | 0.7 | 24 | 0 |
| Psychiatric disorders | ||||
| Insomnia | 12 | 0 | 10 | 0 |
Source: PENPULIMAB-KCQX Prescribing Information
1 Graded per NCI CTCAE v5.0
2 Includes retching
3 Includes blood thyroid stimulating hormone increased and secondary hypothyroidism
4 Includes productive cough and upper-airway cough syndrome
5 Includes asthenia
6 Includes dermatitis, dermatitis acneiform, drug eruption, eczema, rash maculo-papular, rash popular, and rash pustular
7 Includes vertigo
8 Includes acute kidney injury, creatinine renal clearance decreased, glomerular filtration rate decreased, renal failure, and renal impairment
9 Includes arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, myalgia, neck pain, pain in extremity, and spinal pain
Abbreviations: Carb, carboplatin AUC 5; Cis, cisplatin; Gem, gemcitabine NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events
Table 8. Safety Results - Adverse Reactions (≥10%), Trial AK105-202, Safety Population
| Adverse Reaction | PENPULIMAB-KCQX | |
|---|---|---|
| All Grades1 % | Grade 3 or 41 % | |
| Endocrine disorders | ||
| Hypothyroidism2 | 39 | 0 |
| Musculoskeletal and connective tissue disorders | ||
| Musculoskeletal pain3 | 25 | 0.8 |
| Investigations | ||
| Weight decreased | 19 | 1.5 |
| General disorders and administration site conditions | ||
| Pyrexia | 15 | 0 |
| Infections and infestations | ||
| Upper respiratory tract infection | 13 | 0.8 |
| Respiratory, thoracic, and mediastinal disorders | ||
| Cough4 | 11 | 0 |
| Skin and subcutaneous tissue disorders | ||
| Rash5 | 11 | 2.3 |
Source: PENPULIMAB-KCQX Prescribing Information
1 Graded per NCI CTCAE v5.0
2 Includes blood thyroid stimulating hormone increase
3 Includes arthralgia, back pain, bone pain, musculoskeletal chest pain, neck pain, non-cardiac chest pain, and pain in extremity
4 Includes productive cough
5 Includes dermatitis acneiform, eczema, and pemphigoid
Abbreviations: NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of side effects was similar between males and female patients.
- Race: The vast majority of patients were Asian; therefore, differences in the occurrence of side effects could not be determined.
- Age: There was no appreciable difference in side effects between age groups when combining PENPULIMAB-KCQX with cisplatin and gemcitabine in Trial AK105-304. There were too few patients older than 65 years of age in Trial AK105-202 of PENPULIMAB-KCQX as monotherapy to analyze.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
There were 2 patients in Trial AK105-202 and 19 patients in Trial AK105-304 age 65 years or older enrolled into the clinical trials. Analyses of adverse events by age were limited to the PENPULIMAB-KCQX single agent safety dataset.
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.