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Camrelizumab plus apatinib in patients with advanced or recurrent endometrial cancer after failure of at least one prior systemic therapy (CAP 04): a single-arm phase II trial

BMC Medicine volume 22, Article number: 344 (2024) Cite this article

Abstract

Background

The combination of anti-programmed death 1 (PD-1) inhibitors and tyrosine kinase inhibitors is an effective treatment strategy in endometrial cancer. We aimed to explore the efficacy and safety of camrelizumab plus apatinib as an alternative therapeutic option in patients with previously treated endometrial cancer.

Methods

This single-arm Simon’s two-stage phase II trial was conducted at the Fudan University Shanghai Cancer Center. Patients with advanced or recurrent endometrial cancer who had failed at least one prior systemic therapy were screened for potential participation. Eligible patients were treated with intravenous camrelizumab (200 mg d1 q2w) and oral apatinib (250 mg qd) every 4 weeks. The primary end point was the objective response rate (ORR) per RECIST v1.1 in the intention-to-treat principle.

Results

Between January 20, 2020, and October 14, 2022, 36 patients (29 with microsatellite stability/mismatch repair proficient [MSS/pMMR] tumors; two with microsatellite instability-high/mismatch repair deficient [MSI-H/dMMR] tumors) were enrolled and treated. The confirmed ORR was 44.4% (95% CI: 27.9, 61.9) and the disease control rate was 91.7% (95% CI: 77.5, 98.2). The median duration of response was 9.3 (95% CI: 4.3, not reached) months, the median progression-free survival was 6.2 (95% CI: 5.3, 11.1) months, and the median overall survival was 21.0 (95% CI: 13.4, not reached) months during a median follow-up of 14.2 (interquartile range: 10.3, 27.6) months. Treatment-related adverse events of grade 3 or 4 occurred in 20 (55.6%) patients, with the most common being increased γ-glutamyl transferase (27.8%), alanine aminotransferase (16.7%) and aspartate aminotransferase (13.9%), and hypertension (11.1%). No treatment-related death occurred.

Conclusions

Camrelizumab plus apatinib showed promising antitumor activity with manageable toxicity in patients with advanced or recurrent endometrial cancer who had failed at least one prior systemic therapy. The findings of this study support further investigation of camrelizumab plus apatinib as an alternative therapeutic option, especially for patients with MSS/pMMR tumors.

Trial registration

This trial was retrospectively registered with ChiCTR.org.cn, number ChiCTR2000031932.

Peer Review reports

Background

Endometrial cancer is the sixth most commonly diagnosed cancer in women [1], with an ever-increasing incidence of 0.69% per year globally [2]. In China, the age-standardized incidence rate of endometrial cancer has increased by 3.4% per year from 2000 to 2018 in females [3]. Although most patients with endometrial cancer are diagnosed at an early stage, approximately 30% of patients present with advanced disease with regional or distant metastases [4, 5] and more than half of them developed tumor recurrences after first-line therapy [6]. Platinum-based chemotherapy is the cornerstone for the treatment of advanced or recurrent endometrial cancer [7]. However, the treatment options have been historically limited, especially after prior systemic therapy.

Immunotherapy has been changing the treatment landscape of endometrial cancer. Several anti-programmed death 1 (PD-1) or its ligand (PD-L1) inhibitors (pembrolizumab, dostarlimab, avelumab, and nivolumab) have been recommended for the treatment of patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) advanced or recurrent endometrial cancer in the second-line or beyond [8, 9]. However, only 17–33% of patients with advanced or recurrent endometrial cancer are MSI-H/dMMR [10, 11]. Immune checkpoint inhibitors combined with antiangiogenic agents showing synergistic therapeutic effects could be a potential antitumor strategy. To that end, the combination of pembrolizumab and lenvatinib has been investigated and demonstrated promising activity in patients with previously treated advanced or recurrent endometrial cancer [12,13,14,15]. Pembrolizumab in combination with lenvatinib was first approved by the Food and Drug Administration for the treatment of patients with non-MSI-H or MMR proficient (pMMR) advanced endometrial cancer whose disease has progressed on or following prior systemic therapy, by the National Medical Products Administration (NMPA) for the same indication, and also by the European Medicines Agency for the same indication except for no restriction on MMR status.

Camrelizumab is a humanized anti-PD-1 monoclonal antibody that can block the interaction between PD-1 and its ligand (PD-L1). Apatinib is a highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2). Combining camrelizumab with apatinib produced synergistic antitumor activity in a preclinical study. The potential mechanism involved the optimization of the immunosuppressive tumor microenvironment induced by low-dose apatinib [16]. Clinically, camrelizumab in combination with apatinib has demonstrated survival benefits in patients with unresectable hepatocellular carcinoma and has been approved by the NMPA in China [17]. Moreover, this combination has shown encouraging antitumor activity in various types of solid tumors, with a manageable safety profile [18,19,20,21,22]. However, their combination effect in endometrial cancer has not been investigated. We conducted the CAP 04 trial to evaluate the efficacy and safety of camrelizumab plus apatinib in patients with advanced or recurrent endometrial cancer who had failed at least one prior systemic therapy.

Methods

Study design and patients

CAP 04 was a single-arm, open-label phase II trial (www.chictr.org.cn, No. ChiCTR2000031932) enrolled patients from the Fudan University Shanghai Cancer Center. Eligible patients were aged 18 years or older and had histologically confirmed advanced endometrial cancer that had progressed on or following at least one prior systemic therapy. Other inclusion criteria were an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 ~ 1, measurable disease according to the Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), adequate major organ function, and a life expectancy of at least 12 weeks. Patients were staged according to the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging system. MSI/MMR status was not required for patient enrollment. Patients were excluded if they had a history of or active autoimmune disease; immunosuppressive therapy or systemic steroid therapy (≥ 10 mg daily of prednisone equivalent) within 2 weeks before enrollment; known central nervous system metastases; uncontrolled hypertension or heart disease; previous thromboembolic events within 6 months before enrollment; were at risk of developing hemorrhage or thrombosis; had an active infection; or had previously received any immune checkpoint inhibitors. Full eligibility criteria can be found in the study protocol.

Procedures

Patients received camrelizumab (200 mg) intravenously on day 1 every 2 weeks and apatinib (250 mg) orally once daily in 4-week cycles. Treatment could be continued until disease progression, intolerable toxicity, patient’s request, investigator’s decision, or for up to 2 years. Treatment beyond RECIST v1.1 defined disease progression was allowed if the patient was deemed to benefit by the investigators. Toxicity was managed by supportive care, dose reduction, and/or treatment delay or discontinuation. Apatinib could be reduced from once daily to five continuous days per week, or even every other day. The reduced dose of apatinib could not be re-escalated. All patients were followed up monthly after the end of the study treatment for survival and subsequent antitumor treatment.

Tumor response was assessed every 8 weeks for the first 48 weeks and every 12 weeks thereafter according to the RECIST v1.1. Adverse events were monitored throughout the study treatment and continued for an additional 30 days after the last dose of study treatment. All adverse events were graded according to the Common Terminology Criteria for Adverse Events version 5.0. Tumor specimens or biopsies were obtained at baseline after informed consent for exploratory biomarker analyses.

End points

The primary end point was the objective response rate (ORR), defined as the percentage of patients achieving complete response (CR) or partial response (PR) per RECIST v1.1. All responses were confirmed at least 4 (+ 7 days) weeks later. Secondary end points were disease control rate (DCR, defined as the percentage of patients with CR, PR, or stable disease [SD]), time to response (TTR, defined as the time from the date of treatment initiation to the date of first documented CR or PR), duration of response (DoR, defined as the time from the date of first documented CR or PR to the date of first recorded disease progression), time to treatment failure (TTF, defined as the time from the date of treatment initiation to the date of treatment discontinuation for any reason), progression-free survival (PFS, defined as the time from the date of treatment initiation to the date of disease progression or death, whichever occurred first), overall survival (OS, defined as the time from the date of treatment initiation to the date of death), and safety (treatment-related adverse events [TRAEs], immune-related adverse events [irAEs]). Exploratory endpoints were ORR and PFS stratified by MSI/MMR and PD-L1 expression.

Exploratory biomarker analyses

Central testing for MSI and PD-L1 expression status was done in patients with adequate samples at a College of American Pathology and Clinical Laboratory Improvement Amendments-certified lab (Shanghai OrigiMed Co., Ltd), which was sponsored by Jiangsu Hengrui Pharmaceuticals Co., Ltd. Testing for MMR status was done at the Department of Pathology, Fudan University Shanghai Cancer Center. Any previously available data on MSI/MMR and PD-L1 expression status were also collected.

Immunohistochemical (IHC) assay

PD-L1 expression was determined with PD-L1 IHC 22C3 pharmDx assay (Dako, Carpinteria, CA, USA). The combined positive score was calculated as the number of PD-L1 staining cells (tumor cells, macrophages, and lymphocytes) divided by the total number of tumor cells multiplied by 100. MMR status was determined by IHC analysis using the primary antibodies against four MMR proteins, MLH1, PMS2, MSH2, and MSH6. The dMMR was defined as the lack of expression of any of the four MMR proteins. The pMMR was defined as the expressions of all four MMR proteins.

Next-generation sequencing (NGS)

Targeted NGS was performed using a custom hybridization capture panel, the Qirui Onco + assay (Shanghai OrigiMed Co., Ltd). DNA was extracted from FFPE tumor samples using the QIAamp DNA FFPE Tissue Kit (Qiagen). After quality control and concentration quantification, the extracted DNA was used for library construction using the KAPA Hyper Prep Kit (Kapa Biosystems). Hybridization capture was performed with the Qirui Onco + panel (~ 4.5 Mb human genome) containing most exons of 671 cancer-related genes and frequently rearranged introns in cancer. Post-capture libraries were sequenced on the Illumina NovaSeq 6000 instruments (Illumina Inc., San Diego, CA). Sequence reads were then pre-processed and checked for data quality inspection and control, followed by processing with a customized bioinformatics pipeline for variant calls (single nucleotide variant, short insertion and deletion, copy number variation, and gene rearrangement). The variants were examined against an in-house annotation database for clinical curation.

MSI status

MSI was calculated as the number of unstable loci out of the 2174 screened microsatellite loci in the Qirui Onco + assay. MSI-high was defined as 15 or more unstable loci, while MSS was defined as fewer than 15 unstable loci.

Statistical analysis

Simon’s two-stage minimax design was adopted with a one-sided α of 0.025 and a power of 80%. The null hypothesis of an ORR of 15% [23, 24] was tested against the desired alternative hypothesis of an ORR of 35%. Twenty-one patients were planned to be enrolled in the first stage. If at least four responses were observed, an additional 13 patients would be accrued during the second stage. The treatment would be considered promising if 10 or more responses were observed among the 34 patients.

The ORR and DCR were calculated, and the corresponding 95% confidence intervals (CIs) were estimated with the Clopper-Pearson method. The PFS, OS, and DoR were analyzed using the Kaplan–Meier method, and the corresponding 95% CIs were estimated with the Brookmeyer-Crowley method. The TTR and TTF were expressed as median and 95% CIs. Safety outcomes were analyzed descriptively. Post hoc sensitivity analyses of ORR were done in the overall population based on baseline patient characteristics (including age, ECOG performance status, body mass index [BMI], prior treatment line, FIGO stage, histologic feature, prior radiotherapy, prior antiangiogenic therapy, and PD-L1 expression status). All statistical analyses were performed with SAS version 9.4 (SAS® Institute Inc., Cary, NC).

Results

Patient characteristics

Between January 20, 2020, and October 14, 2022, a total of 36 patients were enrolled and treated. All 36 patients were included in the efficacy and safety analyses. As of the data cutoff on June 30, 2023, one patient was still on study treatment. The primary reason for treatment discontinuation was disease progression (66.7%) (Additional file 1: Fig. S1).

Median age of the patients was 60 (range: 29–76) years, with 36.1% (13/36) aged 65 years or older. Almost half (17/36) of the patients had an ECOG performance status score of 1. Mean BMI was 26.5 (range: 19.6, 34.0) kg/m2. Most (77.8%) patients had a histological type of endometrioid adenocarcinoma (FIGO grade I–II: 57.1%; grade III: 39.3%). Fifteen (41.7%) patients had received two or more lines of prior systemic therapy. All patients had received prior platinum plus taxane chemotherapy, 19 (52.8%) had received prior radiotherapy, and 10 (27.8%) had received prior antiangiogenic therapy. The baseline demographic and clinical characteristics of the patients are summarized in Table 1.

Table 1 Baseline characteristics
Full size table

Of the 36 patients, 31 (86.1%) were tested for MSI/MMR status, only two (5.6%) were MSI-H/dMMR; 24 (66.7%) were tested for PD-L1 expression, seven (19.4%) were PD-L1 positive.

Efficacy

Of the 21 patients enrolled in the first stage, 10 (47.6%) achieved the confirmed CR or PR, exceeding the prespecified threshold of 4, and thus the trial proceeded to the second stage. Among the 36 patients finally enrolled, 16 achieved the confirmed CR (n = 3) or PR (n = 13), and 17 had SD, resulting in an ORR of 44.4% (95% CI: 27.9, 61.9) and a DCR of 91.7% (95% CI: 77.5, 98.2) (Table 2). Twenty-seven (75%) patients had tumor shrinkage (Fig. 1a). The median TTR was 1.9 (95% CI: 1.8, 2.5) months. Thirteen (36.1%) patients showed objective responses at the first radiographical assessment (Fig. 1b). The median DoR was 9.3 (95% CI: 4.3, not reached) months, with 11 (30.6%) patients responding for at least 6 months (Fig. 1c). The median TTF was 6.1 (95% CI: 4.0, 10.4) months.

Table 2 Tumor responses
Full size table
Fig. 1
figure 1

Antitumor activity of camrelizumab plus apatinib in patients with advanced or recurrent endometrial cancer who had failed prior systemic therapy. a Waterfall plot showing the best percentage changes from baseline in the sum of diameters of measurable lesions (n = 35). One patient who achieved a complete response had no target lesion; b Spider plot showing percentage change over time from baseline in the sum of diameters of measurable lesions (n = 35). One patient who achieved a complete response had no target lesion; c Swimmer plot showing tumor response and treatment duration (n = 36). CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; PD-L1, programmed death ligand 1; MSI, microsatellite instability; MSI-H, MSI-high; dMMR, mismatch repair deficient; MSS, microsatellite stability; pMMR, mismatch repair proficient

Full size image

At the data cutoff (June 30, 2023), the median follow-up was 14.2 (interquartile range: 10.3, 27.6) months. A total of 28 (77.8%) patients had disease progression or had died. The median PFS was 6.2 (95% CI: 5.3, 11.1) months (Fig. 2a). The median OS was 21.0 (95% CI: 13.4, not reached) months, with a 12-month OS rate of 74.1% (95% CI: 56.0, 85.7) (Fig. 2b).

Fig. 2
figure 2

Kaplan–Meier analyses of progression-free survival (a) and overall survival (b) in patients with advanced or recurrent endometrial cancer receiving camrelizumab plus apatinib

Full size image

Among the 29 patients with MSS/pMMR tumors, 16 (55.2%, 95% CI: 35.7, 73.6) achieved objective responses, and the corresponding median PFS was 8.1 (95% CI: 5.6, 13.0) months. Two patients with MSI-H/dMMR tumors did not respond to camrelizumab plus apatinib. The ORR was 57.1% (95% CI: 18.4, 90.1) for patients with PD-L1-positive tumors and 52.9% (95% CI: 27.8, 77.0) for patients with PD-L1-negative tumors (Additional file 1: Fig. S2). Details regarding PFS and OS stratified by PD-L1 expression are illustrated in Additional file 1: Fig. S3. The ORRs were generally consistent across other subgroups (age, ECOG performance status, BMI, prior treatment line, FIGO stage, histologic feature, prior radiotherapy), except for prior antiangiogenic therapy (Additional file 1: Fig. S2).

Exposure and safety

The median duration of study treatment was 28.8 (range 9.3, 102.4) weeks; the median number of cycles of camrelizumab therapy was 7.1 (ranges: 2, 26); the median duration of apatinib therapy was 27.5 (range: 8.0, 102.4) weeks. The median relative dose intensity (the ratio of the delivered dose intensity to the standard dose intensity) was 83.3% (range: 50, 100) with camrelizumab and 79.8% (range: 42, 100) with apatinib.

TRAEs of any grade occurred in 35 (97.2%) patients, and those of grade 3 or 4 occurred in 20 (55.6%) patients. The most common grade 3 or 4 TRAEs were increased γ-glutamyl transferase (27.8%), increased alanine aminotransferase (16.7%), increased aspartate aminotransferase (13.9%), and hypertension (11.1%) (Table 3). TRAEs led to interruption of any study drugs in 25 (69.4%) patients, dose reduction of apatinib in 19 (52.8%) patients, and discontinuation of any study drugs in 2 (5.6%) patients. No patients discontinued study treatment due to adverse events. No treatment-related death occurred.

Table 3 Treatment-related adverse events (TRAEs) occurring in ≥ 10% of patients and immune-related adverse events (irAEs)
Full size table

IrAEs of any grade occurred in 20 (55.6%) patients, and those of grade 3 or 4 occurred in 12 (33.3%) patients (Table 3). Reactive cutaneous capillary endothelial proliferation (RCCEP) occurred in 7 (19.4%) patients, and all were mild (grade 1 or 2).

Discussion

Camrelizumab plus apatinib has shown encouraging antitumor activity and manageable safety in various types of solid tumors. The CAP 04 trial showed promising antitumor activity, with a well-tolerated safety profile, of camrelizumab plus apatinib in advanced or recurrent endometrial cancer after failure of at least one prior systemic therapy. The positive results of the study support further investigation of camrelizumab plus apatinib as an alternative therapeutic option, especially for patients with MSS/pMMR tumors.

The ORR was 44.4% (RECIST v1.1, 16/36) and the median PFS was 6.2 months with camrelizumab plus apatinib. These data were in line with the previous studies of pembrolizumab plus lenvatinib in the KEYNOTE-146 (irRECIST ORR: 39.8% [43/108], median PFS: 7.4 months) [12] and KEYNOTE-775 (RECIST v1.1 ORR: 31.9% [131/411], median PFS: 7.2 months) [13], nivolumab plus cabozantinib (RECIST v1.1 ORR: 25% [9/36], median PFS: 5.3 months) [25], TQB2450 plus anlotinib (RECIST v1.1 ORR: 33.3% [10/30], median PFS: 6.6 months) [26], and avelumab plus axitinib (RECIST v1.1 ORR: 39.3% [11/28], median PFS: 7.3 months) [27], despite the different tumor response criteria used. However, a previous study of sintilimab plus anlotinib by Wei et al. reported a high ORR of 73.9% (irRECIST) in patients with previously treated advanced or recurrent endometrial cancer, and the median PFS was not reached at the time of data analysis [28].

The introduction of molecular/genomic profiling and immunotherapy would help to tailor treatment in patients with endometrial cancer [29]. MSI-H/dMMR is an agnostic biomarker that has been reported to occur in approximately 30% of patients with primary endometrial cancer [30]. In the study of sintilimab plus anlotinib, 9 (39.1%) of the 23 patients with recurrent endometrial cancer had MSI-H/dMMR tumors. This proportion was substantially higher than that observed in our and other studies (CAP 04: 5.6% [2/36]; nivolumab plus cabozantinib: 5.6% [2/36]; KEYNOTE-146: 10.2% [11/108]; KEYNOTE-775: 15.8% [65/411]). Patients with MSI-H/dMMR tumors seem to benefit more from immunotherapy alone or in combination with antiangiogenic therapy when compared with their MSS/pMMR counterparts (KEYNOTE-146: ORR 63.6% vs 37.2%, median PFS: 26.4 vs 7.4 months; KEYNOTE-775: ORR: 40.0% vs 30.3%, median PFS: 10.7 vs 6.6 months) [12, 13]. Among the 29 (80.6%) patients with MSS/pMMR diseases in our study, 16 achieved an objective response, resulting in a high ORR of 55.2%. By contrast, only two (5.6%) patients had MSI-H/dMMR tumors. The limited number of patients with MSI-H/dMMR tumors precluded the possibility of subgroup comparison regarding MSI/MMR status. The prevalence of MSI/MMR status in Chinese patients with recurrent endometrial cancer and its clinical significance still need further investigation. Nevertheless, these results establish the antitumor activity of camrelizumab plus apatinib in patients with previously treated endometrial cancer, even in MSS/pMMR patients who have limited treatment options.

In addition to MSI/MMR status, the PD-L1 expression status was not associated with the antitumor activity of camrelizumab plus apatinib in patients with previously treated endometrial cancer. These results were partially consistent with the report from the previous studies, which indicated the antitumor activity of pembrolizumab plus lenvatinib and sintilimab plus anlotinib irrespective of PD-L1 expression status [15, 28]. BMI has been identified as a promising biomarker for predicting response to immunotherapy in patients with recurrent gynecologic cancer, with overweight patients (BMI ≥ 25 kg/m2) showing favorable outcomes [31]. In our study, the ORR rate was generally consistent between the patients with BMI ≥ 25 kg/m2 and those with BMI < 25 kg/m2. However, due to the small sample size of patients enrolled for analysis, future studies are required to clarify the prognostic values of these biomarkers. Besides, a small subset of patients with histological types other than endometrial adenocarcinoma were included, such as patients with serous carcinoma (n = 6, 16.7%), although camrelizumab plus apatinib did show potential antitumor activity (ORR: 50% [3/6]) in this subgroup of the patients. Additionally, patients who had received one and two or more prior treatment lines all responded to some extent, while those who had received prior antiangiogenic therapy were less likely to respond. Future studies using a large sample size are needed to clarify it further. By the way, other sustainable methods beyond molecular or genomic profiling, such as radiomics, have been assessed as alternative tools to provide additional information on the treatment and prognosis of endometrial cancer. The integration of these methods may provide new insights into the characterization of endometrial cancer [32].

As for safety, the combination of camrelizumab and apatinib was generally manageable, with no new safety signals. The most common TRAEs were increased γ-glutamyl transferase, increased alanine aminotransferase, hypertension, and increased aspartate aminotransferase. The safety profile of camrelizumab plus apatinib was generally similar to the known profiles of each agent and their combination [18, 33]. The incidence of RCCEP (19.4% [7/36]), a typical camrelizumab-related adverse event, was quite within the range (6 ~ 29%) reported for camrelizumab plus apatinib in various solid tumors [17, 18, 20]. However, it was lower than that reported (67 ~ 81%) for camrelizumab alone or combined with chemotherapy [34,35,36,37,38]. The potential mechanism may involve the inhibition of angiogenesis by anti-VEGFR inhibitors like apatinib, which may decrease the development of RCCEP driven by camrelizumab binding to vascular endothelial growth factor [39, 40].

Unlike most of the previous studies, the present data feature an Asian cohort. However, this study is limited by the single center, single-arm study design, and retrospective registration. Besides, molecular tests for PD-L1 expression, MSI/MMR, and tumor mutation burden (TMB) were done only in some of the patients due to the unavailability or poor quality of tissue samples. In addition to the central targeted NGS for TMB/MSI testing, a fair number of other miscellaneous methods were also used for exploratory analyses (Additional file 2: Table S1). The results of the TMB subgroup analysis are not reported herein, and subgroup analyses for PD-L1 and MSI/MMR status should be interpreted cautiously. Additionally, the follow-up in this study is not long enough to capture the OS of the patients.

Conclusion

Camrelizumab plus apatinib showed promising antitumor activity with manageable toxicity in patients with advanced or recurrent endometrial cancer after failure of at least one prior systemic therapy. The findings of this study support further investigation of the combination therapy with camrelizumab and apatinib as an alternative therapeutic option, especially for patients with MSS/pMMR tumors.

Availability of data and materials

The datasets generated and/or analyzed during the current study are not publicly available due to privacy or ethical restrictions but are available from the corresponding author upon reasonable request.

Abbreviations

PD-1:

Programmed death 1

PD-L1:

Programmed death ligand-1

ORR:

Objective response rate

MSS:

Microsatellite stability

MSI-H:

Microsatellite instability-high

pMMR:

Mismatch repair proficient

dMMR:

Mismatch repair deficient

NMPA:

National Medical Products Administration

VEGFR2:

Vascular endothelial growth factor receptor 2

ECOG:

Eastern Cooperative Oncology Group

RECIST v1.1:

Response Evaluation Criteria In Solid Tumors version 1.1

FIGO:

International Federation of Gynecology and Obstetrics

CR:

Complete response

PR:

Partial response

SD:

Stable disease

DCR:

Disease control rate

TTR:

Time to response

DoR:

Duration of response

TTF:

Time to treatment failure

PFS:

Progression-free survival

OS:

Overall survival

TRAEs:

Treatment-related adverse events

irAEs:

Immune-related adverse events

NGS:

Next-generation sequencing

CIs:

Confidence intervals

BMI:

Body mass index

RCCEP:

Reactive cutaneous capillary endothelial proliferation

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Acknowledgements

We would like to thank the patients and their families for participating in this study. We want to thank the staff of the nursing team, radiology team, and clinical trial pharmacy from Fudan University Shanghai Cancer Center. We also want to thank Ni Guan, Zijin Zhang, and Jinyun Sun from Jiangsu Hengrui Pharmaceuticals Co., Ltd. for their support in data collection, statistical analysis, and medical writing assistance.

Funding

This study was supported by grants from the National Natural Science Foundation of China (No. 82002758) and Technological innovation projects of medicine founded by the Science and Technology Commission of Shanghai Municipality (20Z11900703). The study drugs (camrelizumab and apatinib) were provided by Jiangsu Hengrui Pharmaceuticals Co., Ltd. free of charge.

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Author notes

  1. Wenjuan Tian and Yulan Ren contributed equally to this work.

Authors and Affiliations

  1. Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, 270 Dong’an Road, Xuhui District, Shanghai, 200032, China

    Wenjuan Tian, Yulan Ren, Chuyu Jing, Wei Zhang, Boer Shan, Huijuan Yang, Xi Cheng & Huaying Wang

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Wenjuan Tian, Yulan Ren, Jing Lu, Chuyu Jing, Wei Zhang, Haiming Li, Yi Zhang, Boer Shan, Huijuan Yang, Xi Cheng & Huaying Wang

  3. Department of Radiology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Jing Lu & Haiming Li

  4. Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, Renji Hospital, Shanghai, 200127, China

    Tingting Wang

  5. School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China

    Tingting Wang

  6. Department of Medical Affairs, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, 201210, China

    Zhiguo Hou, Ting Yang & Wenqing Zhu

  7. Department of Nursing, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Yi Zhang

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  1. Wenjuan Tian
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Contributions

HW contributed to the conception, design, and control of the study. WT contributed to patient recruitment and management, data collection and analysis, and manuscript writing. YR recruited patients and collected the data. WZ and CJ contributed to patient management and data collection. JL, HL, and TW evaluated the radiographic examination. BS, HY, and XC contributed to the patient’s recommendation. YZ contributed to the patient’s care. ZH and TY contributed to the literature search, data analysis, and interpretation. QWZ contributed to the statistical analyses. All authors contributed to critically reviewing or revising the manuscript, had full access to all the data in the study, and had final responsibility for the decision to submit for publication. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Huaying Wang.

Ethics declarations

Ethics approval and consent to participate

This study was performed in accordance with the principles of the Declaration of Helsinki, the Good Clinical Practice Guidelines of the International Conference on Harmonization, and the local regulatory requirements. The study protocol and any amendments were approved by the Institutional Review Board (Ref. 1911210–9/-2109B). All patients provided written informed consent before participation.

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Not applicable.

Competing interests

Zhiguo Hou, Ting Yang, and Wenqing Zhu are employees of the Jiangsu Hengrui Pharmaceuticals Co., Ltd. All the other authors declare no competing interests.

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Supplementary Information

12916_2024_3564_MOESM1_ESM.docx

Additional file 1: Figures S1-S3. Fig. S1. Patient flowchart. Fig. S2. Subgroup analyses of objective response rate regarding baseline patient characteristics. Fig. S3. Kaplan-Meier analyses of progression-free survivaland overall survivalstratified by PD-L1 expression.

Additional file 2: Table S1. Data on exploratory biomarker analyses.

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Tian, W., Ren, Y., Lu, J. et al. Camrelizumab plus apatinib in patients with advanced or recurrent endometrial cancer after failure of at least one prior systemic therapy (CAP 04): a single-arm phase II trial. BMC Med 22, 344 (2024). https://doi.org/10.1186/s12916-024-03564-z

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BMC Medicine

ISSN: 1741-7015

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