Cejemly (sugemalimab)

P3, N=560, Not yet recruiting, Akeso

P1/2, N=45, Recruiting, Sichuan University | Not yet recruiting --> Recruiting

P1, N=11, Completed, CStone Pharmaceuticals | Active, not recruiting --> Completed | Phase classification: P1a/1b --> P1 | Trial completion date: Oct 2024 --> Dec 2023

For the overall survival (OS) analysis, no statistically significant differences were observed between pembrolizumab [hazard ratios (HR) = 1.00, 95% CI: 0.94-1.07], sintilimab (HR = 0.99, 95% CI: 0.89-1.09), sugemalimab (HR = 0.98, 95% CI: 0.87-1.10), tislelizumab (HR = 0.97, 95% CI: 0.87-1.09), zolbetuximab (HR = 0.98, 95% CI: 0.91-1.07), and nivolumab (HR = 1.00). In addition, anti-claudin-18.2-targeted therapies presented similar OS (HR = 0.99, 95% CI: 0.95-1.04) and PFS (HR = 1.01, 95% CI: 0.91-1.12) compared to immunotherapy, although their toxicity profiles were distinct. Our network meta-analysis showed no significant difference in PFS, OS, or ORR between different checkpoint inhibitors or between immunotherapy and anti-claudin-18.2-targeted therapies in the first-line treatment of HER2-negative, unresectable, or metastatic gastric cancers.

As a result of great achievements in clinical trials, 6 programmed death-1 inhibitors (sintilimab, camrelizumab, tislelizumab, pembrolizumab, cemiplimab, and nivolumab), 2 programmed death-ligand 1 inhibitors (sugemalimab and atezolizumab), and 1 cytotoxic T lymphocyte-associated antigen-4 inhibitor (ipilimumab) have been approved as first-line treatment for mNSCLC by the US Food and Drug Administration. Results from first-line trials have shown that almost all driver-negative mNSCLC are treated with ICIs and significantly prolong patient survival; however, the low response rate and adverse reactions to immunotherapy remain to be addressed. Here, we summarize the use of ICIs, including monotherapy and combination therapy, in the first-line treatment of mNSCLC in recent years and discuss the low response rate and adverse reactions of ICIs as well as the challenges and expectations for the first-line treatment of mNSCLC in the future.

P1/2, N=45, Not yet recruiting, Sichuan University

P3, N=479, Completed, CStone Pharmaceuticals | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Sep 2023

P3, N=540, Completed, CStone Pharmaceuticals | Active, not recruiting --> Completed

P3, N=150, Not yet recruiting, CStone Pharmaceuticals | Trial completion date: Oct 2027 --> Nov 2028 | Initiation date: Jul 2023 --> Jul 2024 | Trial primary completion date: Oct 2026 --> Nov 2027

P1, N=9, Recruiting, Base Therapeutics (Shanghai) Co., Ltd.

For the PD-L1 non-selective patients, sintilimab plus chemotherapy (sinti-chemo) provided the best OS [hazard ratio (HR) = 0.59, 95% confidence interval (CI):0.42-0.83]. Nivolumab plus bevacizumab plus chemotherapy (nivo-bev-chemo) was comparable to atezolizumab plus bevacizumab plus chemotherapy (atezo-bev-chemo) in prolonging PFS (HR = 0.99, 95% CI: 0.51-1.91)...Subgroup analysis showed pembrolizumab plus chemotherapy (pembro-chemo) ranked first in OS in subgroups of PD-L1 < 1%, non-squamous, no CNS metastases, with or without smoking history, and ranked second in OS in subgroups of PD-L1 ⩾ 1% and PD-L1 1-49%. Cemiplimab and sugemalimab plus chemotherapy ranked first in OS and PFS for squamous subgroup, respectively. For patients with CNS metastases, nivolumab plus ipilimumab plus chemotherapy (nivo-ipili-chemo) and camrelizumab plus chemotherapy provided the best OS and PFS, respectively...Addition of bevacizumab consistently provided with favorable PFS results in patients of all PD-L1 levels. Cemiplimab was the best option in squamous subgroup and nivo-ipili-chemo in CNS metastases subgroup due to their advantages in OS.

Sugema + chemo was not cost-effective as a first-line treatment for either metastatic squamous or metastatic nonsquamous NSCLC in Chinese patients compared with placebo + chemo. However, we found that sugema + chemo would be cost-effective in patients with metastatic squamous and non-squamous NSCLC when sugemalimab's price was decreased by > 39.0% and 64.8%, respectively.

P3, N=105, Not yet recruiting, Zhejiang Cancer Hospital

Methods Eligible pts with previously untreated, no known HER2-positive status, PD-L1 expression ≥5%, unresectable advanced or metastatic G/GEJ adenocarcinoma were randomized 1:1 to receive suge/placebo (1200 mg, Q3W, IV) + CAPOX (capecitabine, 1000 mg/m2, PO, BID, D1-14, Q3W; oxaliplatin, 130 mg/m2, IV, Q3W; max 6 cycles). Table: LBA79 PD-L1 Expression Level >=5% Suge+CAPOX Placebo+CAPOX N=241 N=238 PFS (Months) Median (95% CI) 7.62 (6.37, 7.89) 6.08 (5.06, 6.44) P-value =10% N=130 N=128 PFS (Months) Median (95% CI) 7.79 (6.77, 9.99) 5.52 (4.83, 6.67) P-value 0.0001 HR (95% CI) 0.58 (0.43, 0.77) OS (Months) Median (95% CI) 17.81 (14.36, 21.16) 12.45 (9.89, 13.86) P-value 0.0022 HR (95% CI) 0.64 (0.48, 0.85) Conclusions Sugemalimab in combination with CAPOX demonstrates statistically significant and clinically meaningful improvements in PFS and OS, with a manageable safety profile. These findings support suge+CAPOX as new first-line treatment option for pts with PD-L1 expression ≥5%, advanced G/GEJ adenocarcinoma.

P3, N=479, Active, not recruiting, CStone Pharmaceuticals | Trial completion date: Aug 2024 --> Jun 2025 | Trial primary completion date: Jun 2020 --> May 2023

Study results will help demonstrate the efficacy and tolerability of anti-PD-L1 antibody consolidation therapy in LS-SCLC patients who have not progressed following cCRT or sCRT, and help determine the clinical implications of MRD in LS-SCLC.

P2, N=41, Recruiting, Hunan Cancer Hospital

In this study, 479 treatment-naive patients with stage IV squamous or non-squamous NSCLC without known EGFR sensitizing mutations, ALK, ROS1 or RET fusions were randomized (2:1) to receive 1,200 mg of sugemalimab (n = 320) or placebo (n = 159) every 3 weeks in combination with platinum-based chemotherapy for up to four cycles, followed by maintenance therapy with sugemalimab or placebo for squamous NSCLC and sugemalimab or placebo plus pemetrexed for non-squamous NSCLC. As of 22 November 2021, the prespecified interim OS analysis showed significant improvement with the addition of sugemalimab to chemotherapy (median OS = 25.4 versus 16.9 months; hazard ratio = 0.65; 95% confidence interval = 0.50-0.84; P = 0.0008). Sugemalimab plus chemotherapy provided superior PFS and OS compared to placebo plus chemotherapy, supporting the use of sugemalimab as a first-line treatment option for metastatic NSCLC.

P3, N=381, Completed, CStone Pharmaceuticals | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Apr 2023

P2, N=80, Completed, CStone Pharmaceuticals | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Mar 2023 | Trial primary completion date: Dec 2023 --> Mar 2023

From the perspective of Chinese healthcare system, sugemalimab consolidation therapy was not a cost-effective strategy in cCRT and sCRT patients with unresectable stage III NSCLC. Given that the sugemalimab PAP was available, sugemalimab consolidation therapy became a cost-effective option.

Sugemalimab showed robust and durable antitumor activity in R/R ENKTL. Treatment was well tolerated with expected safety profile for this drug class.

Sugemalimab (Suge), an anti-PD-L1 monoclonal antibody, plus fluorouracil and cisplatin (FP) regimen demonstrated preliminary anti-tumor activity in a phase 1b cohort of patients (pts) with advanced ESCC. Suge plus FP demonstrated statistically significant and clinically meaningful prolongation of PFS and OS, and improvement of ORR compared with Pbo plus FP. The safety profile was manageable with no new safety signals detected. These results support the use of Suge plus FP as 1L treatment for unresectable locally advanced, recurrent or metastatic ESCC.

P3, N=540, Active, not recruiting, CStone Pharmaceuticals | Trial completion date: Dec 2023 --> Mar 2024 | Trial primary completion date: Jul 2023 --> Dec 2023

Preliminary data showed that BLU-554 in combination with CS1001 is safe and effective for treatment of patients with locally advanced or metastatic HCC.

P3, N=479, Active, not recruiting, CStone Pharmaceuticals | Trial primary completion date: Aug 2022 --> May 2023

P1/2, N=26, Completed, CStone Pharmaceuticals | Unknown status --> Completed | N=52 --> 26

Sensitivity analysis results suggested that the model outcomes were reliable. From the perspective of Chinese healthcare system, the SC was not cost-effective in comparison to PC as first-line treatment for NSCLC, regardless of PD-L1 tumor expression level and pathological subtype.

P3, N=479, Active, not recruiting, CStone Pharmaceuticals | Trial primary completion date: Apr 2022 --> Sep 2022

P1/2, N=19, Completed, CStone Pharmaceuticals | Recruiting --> Completed | N=150 --> 19 | Trial completion date: Jul 2023 --> Aug 2021 | Trial primary completion date: Dec 2022 --> May 2021

In December 2021, sugemalimab was approved in China for the first-line treatment of epidermal growth factor receptor (EGFR) gene mutation and anaplastic lymphoma kinase (ALK) negative metastatic non-small cell lung cancer (NSCLC) administered in combination with pemetrexed and carboplatin for non-squamous NSCLC and in combination with paclitaxel and carboplatin for squamous NSCLC. Clinical studies assessing sugemalimab for the treatment of several other cancers, including liver cancer, gastric cancer, oesophageal cancer, Hodgkin lymphoma and extranodal natural killer/T cell lymphoma are underway in China, the US and Australia. This article summarizes the milestones in the development of sugemalimab leading to this first approval for the first-line treatment of EGFR gene mutation and ALK-negative metastatic NSCLC.

P3, N=540, Active, not recruiting, CStone Pharmaceuticals | Recruiting --> Active, not recruiting

PD-L1 monotherapy may not be sufficient to block the PD-1 pathway; PD-L2 was expressed in HRS and background cells in cHL. The immunologic function of the PD-L2 pathway in anti-tumor activity may be underestimated in R/R cHL. Further study is needed to elucidate the anti-tumor mechanism of PD-1 inhibitor and PD-L1 inhibitor treatment.

Sugemalimab plus chemotherapy showed a statistically significant and clinically meaningful progression-free survival improvement compared with placebo plus chemotherapy, in patients with previously untreated squamous and non-squamous metastatic NSCLC, regardless of PD-L1 expression, and could be a newfirst-line treatment option for both squamous and non-squamous metastatic NSCLC.

P3, N=479, Active, not recruiting, CStone Pharmaceuticals | Recruiting --> Active, not recruiting

Sugemalimab was well-tolerated and showed promising antitumor activity as monotherapy or in combination with SOC chemotherapy in advanced malignancies. This trial was registered with ClinicalTrials.gov on Oct 18, 2017, number NCT03312842.

P3, N=479, Active, not recruiting, CStone Pharmaceuticals | Recruiting --> Active, not recruiting | Trial primary completion date: Sep 2020 --> Jun 2020

So far three therapeutic anti-PD-L1 antibodies (atezolizumab, avelumab, durvalumab) have been approved by US FDA in different cancer indications. CS1001 monotherapy or combo with chemotherapy or targeted therapy were safe and well tolerated. CS1001 demonstrated promising efficacy in multiple tumor types and support full development of CS1001 as mono/combo therapy for multiple indications in ongoing and planned clinical trials including cHL, ENKTL, GC, EC, and NSCLC.

Pts with non-squamous (nsq)-NSCLC received 4-6 cycles of CS1001 (1200 mg, IV, Q3W), carboplatin (AUC = 5), and pemetrexed (500 mg/m2), followed by maintenance therapy with CS1001 and pemetrexed. Pts with squamous (sq)-NSCLC received CS1001 (1200 mg, IV, Q3W), carboplatin (AUC = 5), and paclitaxel (175 mg/m2), followed by maintenance therapy with CS1001... The combination of CS1001 and platinum-based chemo regimen demonstrated promising anti-tumor activity with a tolerable safety profile. The results of this study support further evaluation of CS1001 and platinum-based chemo in 1L NSCLC. Currently, a randomized phase III study (NCT03789604) of this treatment regimen in pts with chemo-naive advanced NSCLC is recruiting pts in China.

P3, N=420, Recruiting, CStone Pharmaceuticals | Not yet recruiting --> Recruiting

P1/2, N=138, Recruiting, CStone Pharmaceuticals | Not yet recruiting --> Recruiting

P1/2, N=138, Not yet recruiting, CStone Pharmaceuticals