Sugemalimab + Chemo Erstlinie NSCLC Stadium IV
Lungenkarzinom · Version 5.1
PICO 05 - NSCLC Patient*innen/Sugemalimab + Chemo
Intervention: Sugemalimab + platin-basierte Kombinationschemotherapie, gefolgt von Erhaltungstherapie mit Sugemalimab
Control: Chemotherapie
Setting:
Time:
Info:
Outcome: Overall survival
Studien
- Zhou, C. et al., 2022, Sugemalimab versus placebo, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer (GEMSTONE-302): interim and final analyses of a double-blind, randomised, phase 3 clinical trial
- Zhou, C. et al., 2025, Sugemalimab versus placebo, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer (GEMSTONE-302): 4-year outcomes from a double-blind, randomised, phase 3 trial
Einleitung
Die systematische Suche nach randomisiert kontrollierten Studien (RCTs) ergab die randomisierte, multizentrische Phase-3-Studie GEMSTONE-302 (NCT03789604). Die Ergebnisse der Zwischen- und Endauswertung sind in der Publikation von Zhou et al. 2022 veröffentlicht, die Ergebnisse zum Gesamtüberleben wurden in Zhou et al. 2025 (4-Jahres-Outcome) veröffentlicht. Die Studie wurde an 35 Zentren, ausschließlich in China, durchgeführt.
Randomisiert (2:1) und ausgewertet wurden 479 Patienten mit „non-small-cell lung cancer (NSCLC) Stadium IV (squamous or non-squamous)“ ohne bekannte EGFR-Mutation, die als Erstlinientherapie entweder mit Sugemalimab plus platinbasierter Chemotherapie (Interventionsgruppe) oder Placebo plus platinbasierter Chemotherapie (Vergleichsgruppe) therapiert wurden (vier Zyklen alle drei Wochen). Im Anschluss wurde als Maintenance-Therapie Sugemalimab bzw. Placebo gegeben. Datencut für das Outcome Gesamtüberleben war der 15. Mai 2023. Der mediane follow-up-Zeitraum betrug zu diesem Zeitpunkt 43,5 Monate (IQR 41,2–46,9) In der Sugemalimab-Gruppe und 43,0 Monate (40,7–44,8) in der Placebo Gruppe. Basierend auf der Entscheidung des Sponsors, wurde die Studie wurde am 15 Mai 2023 beendet und alle Patienten brachen die Studienbehandlung ab.
Eine Behandlung mit Sugemalimab plus Chemotherapie resultierte in einem verlängerten Gesamtüberleben im Vergleich zu der Behandlung mit Placebo plus Chemotherapie. Das mittlere Gesamtüberleben (overall survival, OS) war in der Sugemalimab-plus-Chemotherapie-Gruppe mit 25,2 Monaten länger als in der Vergleichsgruppe (16,9 Monate, HR 0,68 (95 %-KI 0,54–0,85)). Weitere Details können der unten stehenden Tabelle entnommen werden.
Die 4-Jahres-Gesamtüberlebensrate betrug in der Sugemalimab-Gruppe 32,1 % und in der Placebo-Gruppe 17,3 %. So dass sich auch hier ein Überlebensvorteil der Sugemalimab-Therapie gegenüber der Placebo-Behandlung zeigte.
Da es sich bei der Studie um ein RCT handelt, wird die Qualität der vorliegenden Evidenz entsprechend der GRADE-Methode für das Outcome Gesamtüberleben HOCH (⊕⊕⊕⊕) bewertet. Aktuell sind keine Abwertungen erfolgt.
| Study details | Study quality | Studycharacteristics | Indirectness | Participants | Effect | ||||
| Author Zhou, C. et al. 2022 Study type Randomized_Controlled_Trial |
Low Risk |
Population 479 patients with metastatic NSCLC (enrolled and randomized) All patients were Asian. Overall, 257 (80%) of 320 patients in the sugemalimab group and 124 (78%) of 159 in the placebo group completed four cycles of chemotherapy. In the placebo group, 44 (28%) of 159 patients crossed over to receive at least one dose of sugemalimab monotherapy and 20 (13%) of 159 received subsequent immunotherapy other than sugemalimab. |
Intervention Sugemalimab (1200 mg, intravenously), n = 320 in combination with platinum-based chemotherapy (carboplatin (AUC 5 mg/mL per min) and pemetrexed (500 mg/m²)/paclitaxel (175 mg/m²) i.v. on day 1 of every 3-week cycle, for up to four cycles, followed by maintenance treatment with pemetrexed/paclitaxel plus sugemalimab Sugemalimab or placebo treatment was administered for up to 35 cycles, or until disease progression or unacceptable toxicity. |
Control Placebo, n = 159 in combination with platinum-based chemotherapy (carboplatin (AUC 5 mg/mL per min) and pemetrexed (500 mg/m²)/paclitaxel (175 mg/m²) i.v. on day 1 of every 3-week cycle, for up to four cycles, followed by maintenance treatment with pemetrexed/paclitaxel plus placebo |
Outcome Overall survival Overall survival data of this trial are reported in Zhou et al. 2025 - 4-year follow-up results. |
no 100 % asiatic study population |
Intervention Event |
Control Event |
Results per outcome |
| Author Zhou, C. et al. 2025 Study type Randomized_Controlled_Trial |
Low Risk Anmerkungen: ROB-2 assessment refers to NCT03789604 in general. |
Population 4 year follow-up of GEMSTONE-302/NCT03789604. Further results described in Zhou et al. 2022 479 patients with metastatic NSCLC (enrolled and randomized) All patients were Asian. Overall, 257 (80%) of 320 patients in the sugemalimab group and 124 (78%) of 159 in the placebo group completed four cycles of chemotherapy. In the placebo group, 44 (28%) of 159 patients crossed over to receive at least one dose of sugemalimab monotherapy and 20 (13%) of 159 received subsequent immunotherapy other than sugemalimab. |
Intervention Sugemalimab (1200 mg, intravenously), n = 320 in combination with platinum-based chemotherapy (carboplatin (AUC 5 mg/mL per min) and pemetrexed (500 mg/m²)/paclitaxel (175 mg/m²) i.v. on day 1 of every 3-week cycle, for up to four cycles, followed by maintenance treatment with pemetrexed/paclitaxel plus sugemalimab Sugemalimab or placebo treatment was administered for up to 35 cycles, or until disease progression or unacceptable toxicity. |
Control Placebo, n = 159 in combination with platinum-based chemotherapy (carboplatin (AUC 5 mg/mL per min) and pemetrexed (500 mg/m²)/paclitaxel (175 mg/m²) i.v. on day 1 of every 3-week cycle, for up to four cycles, followed by maintenance treatment with pemetrexed/paclitaxel plus placebo |
Outcome Overall survival defined as time from randomisation to death from any cause |
no 100 % asiatic study population |
Intervention Event Death events occurred in 203/320 (63%) patients. Median overall survival was 25.2 months (95% CI 20.1–30.2). 4-year overall survival rate was 32.1 % (26.7 - 37.6 ). |
Control Event Death events occurred in 116/159 (73%) patients. Median overall survival was 16.9 months (95% CI 12.8–20.7). 4-year overall survival rate was 17.3 % (11.1 - 24.7). |
Results per outcome Median overall survival HR 0.68 (95 % CI 0.54 - 0.85) |
| GRADE appraisal | ||||||||
| Study type | Outcome / description | Literature | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | GRADE |
| RCT | Overall survival | Zhou, C. et al., 2022, Zhou, C. et al., 2025 | not serious | not serious | not serious See footnote 1 |
not serious | Publication bias: Undetected |
Following the approach of the GRADE Working Group, the overall quality of evidence for the endpoint “Overall survival” was rated as High ⊕⊕⊕⊕ |
Footnotes
1Indirectness
After consultation with clinical experts there is no indirectness due to the study population.
Outcome: Progression-free survival
Studien
- Zhou, C. et al., 2022, Sugemalimab versus placebo, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer (GEMSTONE-302): interim and final analyses of a double-blind, randomised, phase 3 clinical trial
- Zhou, C. et al., 2025, Sugemalimab versus placebo, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer (GEMSTONE-302): 4-year outcomes from a double-blind, randomised, phase 3 trial
Einleitung
Die systematische Suche nach randomisiert kontrollierten Studien (RCTs) ergab die randomisierte, multizentrische Phase-3-Studie GEMSTONE-302 (NCT03789604). Die Ergebnisse der Zwischen- und Endauswertung sind in der Publikation von Zhou et al. 2022 veröffentlicht, die Ergebnisse zum Gesamtüberleben wurden in Zhou et al. 2025 (4-Jahres-Outcome) veröffentlicht. Die Studie wurde an 35 Zentren, ausschließlich in China, durchgeführt.
Randomisiert (2:1) und ausgewertet wurden 479 Patienten mit „non-small-cell lung cancer (NSCLC) Stadium IV (squamous or non-squamous)“ ohne bekannte EGFR-Mutation, die als Erstlinientherapie entweder mit Sugemalimab plus platinbasierter Chemotherapie (Interventionsgruppe) oder Placebo plus platinbasierter Chemotherapie (Vergleichsgruppe) therapiert wurden (vier Zyklen alle drei Wochen). Im Anschluss wurde als Maintenance-Therapie Sugemalimab bzw. Placebo gegeben. Das progressionsfreie Überleben wurde nach einem medianen follow-up-Zeitraum von 8,6 Monaten (IQR 6·1–11·4) mit Datenschnitt am 8. Juni 2020 analysiert (vorab festgelegten Zeitpunkt für das primäre Outcome).
Eine Behandlung mit Sugemalimab plus Chemotherapie resultierte in einem signifikant längeren progressionsfreien Überleben (progression-free survival, PFS) im Vergleich zu der Behandlung mit Placebo plus Chemotherapie. Das mittlere PFS (zum Zeitpunkt der Zwischenauswertung, 8. Juni 2020) lag in der Sugemalimab-plus-Chemotherapie-Gruppe bei 7,8 Monaten im Vergleich zu 4,9 Monaten in der Placebogruppe (HR 0,50 (95 %-KI 0,39–0,64)).
Die geschätzte 12-Monats-PFS-Rate lag in der Sugemalimab-Gruppe bei 36,4 % und in der Placebo-Gruppe bei 14,8 %. Weitere Details können der unten stehenden Tabelle entnommen werden.
Da es sich bei der Studie um ein RCT handelt, wird die Qualität der vorliegenden Evidenz entsprechend der GRADE-Methode für das Outcome „progressionsfreies Überleben“ HOCH (⊕⊕⊕⊕) bewertet. Aktuell sind keine Abwertungen erfolgt.
| Study details | Study quality | Studycharacteristics | Indirectness | Participants | Effect | ||||
| Author Zhou, C. et al. 2022 Study type Randomized_Controlled_Trial |
Low Risk |
Population 479 patients with metastatic NSCLC (enrolled and randomized) All patients were Asian. Overall, 257 (80%) of 320 patients in the sugemalimab group and 124 (78%) of 159 in the placebo group completed four cycles of chemotherapy. In the placebo group, 44 (28%) of 159 patients crossed over to receive at least one dose of sugemalimab monotherapy and 20 (13%) of 159 received subsequent immunotherapy other than sugemalimab. |
Intervention Sugemalimab (1200 mg, intravenously), n = 320 in combination with platinum-based chemotherapy (carboplatin (AUC 5 mg/mL per min) and pemetrexed (500 mg/m²)/paclitaxel (175 mg/m²) i.v. on day 1 of every 3-week cycle, for up to four cycles, followed by maintenance treatment with pemetrexed/paclitaxel plus sugemalimab Sugemalimab or placebo treatment was administered for up to 35 cycles, or until disease progression or unacceptable toxicity. |
Control Placebo, n = 159 in combination with platinum-based chemotherapy (carboplatin (AUC 5 mg/mL per min) and pemetrexed (500 mg/m²)/paclitaxel (175 mg/m²) i.v. on day 1 of every 3-week cycle, for up to four cycles, followed by maintenance treatment with pemetrexed/paclitaxel plus placebo |
Outcome Progression-free survival investigator-assessed; defined as time from randomisation to disease progression according to RECIST version 1.1 or death from any cause, whichever occurred first, in the intention-to-treat population (data cutoff June 8, 2020). |
no 100 % asiatic study population |
Intervention Event Progression or death events occurred in 155 (48%) of 320 patients with sugemalimab (data cutoff June 8, 2020). Median progression-free survival was 7.8 months (95% CI 6.9–9.0). Estimated 12-month progression-free survival rate: 36.4% (95% CI 31.0–41.8) |
Control Event Progression or death events occurred in 1113 (71%) of 159 with placebo (data cutoff June 8, 2020). Median progression-free survival was 4.9 (4.7–5.0) months. Estimated 12-month progression-free survival rate: 14.8% (95% CI 9.7–21.1) |
Results per outcome data cutoff March 15, 2021; median follow-up 17·8 months [IQR 15·1–20·9] At the prespecified interim analysis (data cutoff June 8, 2020) HR 0.50 (95 % CI 0.39 - 0.64), p < 0.0001. data cutoff March 15, 2021: HR 0.48, 95% CI 0.39–0.60; p < 0·0001. |
| Author Zhou, C. et al. 2025 Study type Randomized_Controlled_Trial |
Low Risk Anmerkungen: ROB-2 assessment refers to NCT03789604 in general. |
Population 4 year follow-up of GEMSTONE-302/NCT03789604. Further results described in Zhou et al. 2022 479 patients with metastatic NSCLC (enrolled and randomized) All patients were Asian. Overall, 257 (80%) of 320 patients in the sugemalimab group and 124 (78%) of 159 in the placebo group completed four cycles of chemotherapy. In the placebo group, 44 (28%) of 159 patients crossed over to receive at least one dose of sugemalimab monotherapy and 20 (13%) of 159 received subsequent immunotherapy other than sugemalimab. |
Intervention Sugemalimab (1200 mg, intravenously), n = 320 in combination with platinum-based chemotherapy (carboplatin (AUC 5 mg/mL per min) and pemetrexed (500 mg/m²)/paclitaxel (175 mg/m²) i.v. on day 1 of every 3-week cycle, for up to four cycles, followed by maintenance treatment with pemetrexed/paclitaxel plus sugemalimab Sugemalimab or placebo treatment was administered for up to 35 cycles, or until disease progression or unacceptable toxicity. |
Control Placebo, n = 159 in combination with platinum-based chemotherapy (carboplatin (AUC 5 mg/mL per min) and pemetrexed (500 mg/m²)/paclitaxel (175 mg/m²) i.v. on day 1 of every 3-week cycle, for up to four cycles, followed by maintenance treatment with pemetrexed/paclitaxel plus placebo |
Outcome Progression-free survival investigator-assessed; defined as time from randomisation to disease progression according to RECIST version 1.1 or death from any cause, whichever occurred first, in the intention-to-treat population. |
no 100 % asiatic study population |
Intervention Event 4-year PFS: 12.4 % (6.9 - 19.6) |
Control Event 4-year PFS: not estimable |
Results per outcome |
| GRADE appraisal | ||||||||
| Study type | Outcome / description | Literature | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | GRADE |
| RCT | progression-free survival | Zhou, C. et al., 2022, Zhou, C. et al., 2025 | not serious | not serious | not serious See footnote 1 |
not serious | Publication bias: Undetected |
Following the approach of the GRADE Working Group, the overall quality of evidence for the endpoint “Progression-free survival” was rated as High ⊕⊕⊕⊕ |
Footnotes
1Indirectness
After consultation with clinical experts there is no indirectness due to the study population.
Outcome: UE
Studien
- Zhou, C. et al., 2022, Sugemalimab versus placebo, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer (GEMSTONE-302): interim and final analyses of a double-blind, randomised, phase 3 clinical trial
- Zhou, C. et al., 2025, Sugemalimab versus placebo, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer (GEMSTONE-302): 4-year outcomes from a double-blind, randomised, phase 3 trial
Einleitung
Die systematische Suche nach randomisiert kontrollierten Studien (RCTs) ergab die randomisierte, multizentrische Phase-3-Studie GEMSTONE-302 (NCT03789604). Die Ergebnisse der Zwischen- und Endauswertung sind in der Publikation von Zhou et al. 2022 veröffentlicht, die Ergebnisse zum Gesamtüberleben wurden in Zhou et al. 2025 (4-Jahres-Outcome) veröffentlicht. Die Studie wurde an 35 Zentren, ausschließlich in China, durchgeführt.
Randomisiert (2:1) und ausgewertet wurden 479 Patienten mit „non-small-cell lung cancer (NSCLC) Stadium IV (squamous or non-squamous)“ ohne bekannte EGFR-Mutation, die als Erstlinientherapie entweder mit Sugemalimab plus platinbasierter Chemotherapie (Interventionsgruppe) oder Placebo plus platinbasierter Chemotherapie (Vergleichsgruppe) therapiert wurden (vier Zyklen alle drei Wochen). Im Anschluss wurde als Maintenance-Therapie Sugemalimab bzw. Placebo gegeben.
In der Interventionsgruppe kam es häufiger zu unerwarteten Ereignissen (UE, adverse events AE) als in der Vergleichsgruppe. So kam es im Beobachtungszeitraum zu 10 (3 %) Todesfällen in der Sugemalimab plus Chemotherapie-Gruppe, während es in der Placebo-Gruppe zu zwei (1 %) Todesfällen kam, die auf unerwartete Ereignisse durch die Studienbehandlung zurückzuführen waren (treatment-related adverse events, TRAE).
Auch die Zahl der schwerwiegenden unerwünschten Ereignisse, die auf die Behandlung zurückzuführen waren, war in der Sugemalimab plus Chemotherapie-Gruppe mit 26 % (82 Patient*innen) höher als in der Placebo-Gruppe mit 20 % (31 Patient*innen). Weitere Details können der unten stehenden Tabelle entnommen werden.
Da es sich bei der Studie um ein RCT handelt, wird die Qualität der vorliegenden Evidenz entsprechend der GRADE-Methode für das Outcome „Unerwartete Ereignisse“ HOCH (⊕⊕⊕⊕) bewertet. Aktuell sind keine Abwertungen erfolgt.
| Study details | Study quality | Studycharacteristics | Indirectness | Participants | Effect | ||||
| Author Zhou, C. et al. 2022 Study type Randomized_Controlled_Trial |
Low Risk |
Population 479 patients with metastatic NSCLC (enrolled and randomized) All patients were Asian. Overall, 257 (80%) of 320 patients in the sugemalimab group and 124 (78%) of 159 in the placebo group completed four cycles of chemotherapy. In the placebo group, 44 (28%) of 159 patients crossed over to receive at least one dose of sugemalimab monotherapy and 20 (13%) of 159 received subsequent immunotherapy other than sugemalimab. |
Intervention Sugemalimab (1200 mg, intravenously), n = 320 in combination with platinum-based chemotherapy (carboplatin (AUC 5 mg/mL per min) and pemetrexed (500 mg/m²)/paclitaxel (175 mg/m²) i.v. on day 1 of every 3-week cycle, for up to four cycles, followed by maintenance treatment with pemetrexed/paclitaxel plus sugemalimab Sugemalimab or placebo treatment was administered for up to 35 cycles, or until disease progression or unacceptable toxicity. |
Control Placebo, n = 159 in combination with platinum-based chemotherapy (carboplatin (AUC 5 mg/mL per min) and pemetrexed (500 mg/m²)/paclitaxel (175 mg/m²) i.v. on day 1 of every 3-week cycle, for up to four cycles, followed by maintenance treatment with pemetrexed/paclitaxel plus placebo |
Outcome UE Adverse events were monitored throughout the study and graded according to the US National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 |
no 100 % asiatic study population |
Intervention Event |
Control Event |
Results per outcome Treatment-emergent adverse events were reported in 319 (>99%) of 320 patients in the sugemalimab group and 157 (99%) of 159 patients in the placebo group. Rates of treatment-emergent adverse events, grade 3–4 treatment-emergent adverse events, and fatal treatment-emergent adverse events were generally similar between the two groups. The most common grade 3 or 4 any treatment-related adverse events were neutrophil count decreased (104 [33%] of 320 with sugemalimab vs 52 [33%] of 159 with placebo), white blood cell count decreased (45 [14%] vs 27 [17%]), anaemia (43 [13%] vs 18 [11%]), platelet count decreased (33 [10%] vs 15 [9%]), and neutropenia (12 [4%] vs seven [4%]). Any treatment-related deaths were reported in ten (3%) patients in the sugemalimab group (pneumonia with respiratory failure in one patient; myelosuppression with septic shock in one patient; pneumonia in two patients; respiratory failure, abdominal pain, cardiac failure, and immune-mediated pneumonitis in one patient each; the other two deaths had an unspecified cause) and in two (1%) patients in the placebo group (pneumonia and multiple organ dysfunction syndrome). |
| Author Zhou, C. et al. 2025 Study type Randomized_Controlled_Trial |
Low Risk Anmerkungen: ROB-2 assessment refers to NCT03789604 in general. |
Population 4 year follow-up of GEMSTONE-302/NCT03789604. Further results described in Zhou et al. 2022 479 patients with metastatic NSCLC (enrolled and randomized) All patients were Asian. Overall, 257 (80%) of 320 patients in the sugemalimab group and 124 (78%) of 159 in the placebo group completed four cycles of chemotherapy. In the placebo group, 44 (28%) of 159 patients crossed over to receive at least one dose of sugemalimab monotherapy and 20 (13%) of 159 received subsequent immunotherapy other than sugemalimab. |
Intervention Sugemalimab (1200 mg, intravenously), n = 320 in combination with platinum-based chemotherapy (carboplatin (AUC 5 mg/mL per min) and pemetrexed (500 mg/m²)/paclitaxel (175 mg/m²) i.v. on day 1 of every 3-week cycle, for up to four cycles, followed by maintenance treatment with pemetrexed/paclitaxel plus sugemalimab Sugemalimab or placebo treatment was administered for up to 35 cycles, or until disease progression or unacceptable toxicity. |
Control Placebo, n = 159 in combination with platinum-based chemotherapy (carboplatin (AUC 5 mg/mL per min) and pemetrexed (500 mg/m²)/paclitaxel (175 mg/m²) i.v. on day 1 of every 3-week cycle, for up to four cycles, followed by maintenance treatment with pemetrexed/paclitaxel plus placebo |
Outcome UE n/a |
no 100 % asiatic study population |
Intervention Event |
Control Event |
Results per outcome The most common grade 3–4 treatment related adverse events were decreased neutrophil count (105 [33%] with sugemalimab vs 52 [33%] with placebo), decreased white blood cell count (48 [15%] vs 27 [17%]), anaemia (44 [14%] vs 18 [11%]), and decreased platelet count (35 [11%] vs 15 [9%]). Treatment-related serious adverse events occurred in 82 (26%) patients with sugemalimab and 31 (20%) with placebo. No additional treatment-related deaths occurred since the previous overall survival interim analysis. No new safety signals were identified. |
| GRADE appraisal | ||||||||
| Study type | Outcome / description | Literature | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | GRADE |
| RCT | adverse events | Zhou, C. et al., 2022, Zhou, C. et al., 2025 | not serious | not serious | not serious See footnote 1 |
not serious | Publication bias: Undetected |
Following the approach of the GRADE Working Group, the overall quality of evidence for the endpoint “UE” was rated as High ⊕⊕⊕⊕ |
Footnotes
1Indirectness
After consultation with clinical experts there is no indirectness due to the study population.