Camrelizumab Plus Famitinib Shows Promise in Recurrent or Metastatic Cervical Cancer

The combination comprised of camrelizumab (SHR-1210) and famitinib (SHR1020) showcased improved efficacy with a manageable safety profile vs camrelizumab monotherapy or investigator’s choice of chemotherapy in patients with recurrent or metastatic cervical cancer, according to data from a phase 2 trial (NCT04680988) presented at the 2023 ESMO Congress.¹

The doublet (n = 105) elicited an objective response rate (ORR) of 41.0% (95% CI, 31.5%-51.0%) by blinded independent central review (BICR) vs 24.1% (95% CI, 13.5%-37.6%) with camrelizumab monotherapy (n = 54), translating to a percentage difference of 16.9% (P = .0181). The disease control rates (DCRs) per BICR were 75.2% (95% CI, 65.9%-83.1%) and 55.6% (95% CI, 41.4%-69.1%), respectively, which equated to a 19.7% percentage difference (P = .0061).

“Camrelizumab plus famitinib represents a novel treatment option for this patient population,” Xiaohua Wu, MD, PhD, of the Department of Gynecologic Oncology at Fudan University Shanghai Cancer Center in Shanghai, China, said in a presentation of the data.

Although patients with early-stage cervical cancer are typically treated with radical surgery and radiotherapy, most will experience disease recurrence or metastasis within 2 years. Those with metastatic cervical cancer have a poor prognosis and have limited therapeutic options available to them. As such, there is a significant unmet need, especially for second- and later-line approaches, according to Wu.

Data from a prior multicohort phase 2 study (NCT03827837) indicated that camrelizumab plus famitinib could provide durable activity with acceptable tolerability in patients with previously treated patients with relapsed or metastatic cervical squamous cell carcinoma.² At a median follow-up of 13.6 months (interquartile range, 10.0-23.6), the doublet elicited an ORR of 39.4% (95% CI, 22.9%-57.9%) in this population (n = 33). The median progression-free survival (PFS) was 10.3 months (95% CI, 3.5-not reached [NR]), and the 12-months overall survival (OS) rate was 77.7% (95% CI, 58.9%-88.7%).

The current phase 2 study enrolled patients with histopathologically confirmed recurrent or metastatic cervical cancer who were not able to receive radical treatment. Patients could have squamous cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma. They must have experienced disease progression or have relapsed following platinum-based chemotherapy and could not have previously received more than 2 lines of systemic treatment. They were required to have an ECOG performance status of 0 or 1 and at least 1 measurable lesion per RECIST v1.1 criteria.

Study participants were randomly assigned 2:1:2 to receive camrelizumab at 200 mg intravenously (IV) every 3 weeks plus famitinib at 20 mg orally (cohort A), IV camrelizumab at 200 mg every 3 weeks (cohort B), or investigator’s choice of chemotherapy (n = 35; cohort C). Those in cohort C could have received nab-paclitaxel at 260 mg/m2 on day 1 every 3 weeks or 125 mg/m2 on days 1, 8, and 15 every 4 weeks; pemetrexed at 500 mg/m2 on day 1 every 3 weeks; or gemcitabine at 1000 mg/m2 on days 1 and 8 every 3 weeks. Treatment continued until progressive disease, intolerable toxicity, withdrawn consent, investigator decision, or loss to follow-up.

Patients were stratified based on histologic subtyping (squamous cell carcinoma vs nonsquamous cell carcinoma) and PD-L1 expression (combined positive score [CPS] of 1 or higher vs CPS of less than 1).

The primary end point of the trial was ORR by BICR for cohort A vs cohort B. Key secondary end points included PFS, OS, ORR by investigator assessment, DCR, time to response (TTR), time to failure (TTF), and safety.

A total of 194 patients underwent randomization. Of the 105 patients in the doublet arm, 105 ended up receiving treatment. At the time of the data cutoff date of April 21, 2021, a total of 70 patients discontinued camrelizumab due to reasons that included radiographical progression (n = 47), patient decision (n = 10), physician decision (n = 4), adverse effects (AEs; n = 3), deaths (n = 3), at least 1 year of the agent after achieving confirmed complete response (CR; n = 1), clinical progression (n = 1), or other (n = 1). A total of 77 patients discontinued famitinib; 41 patients had radiographical progression, 18 had AEs, 9 patients decided to withdraw, 4 patients discontinued due to physician decision, 3 patients died, 1 patient received at least 1 year of the agent after achieving confirmed CR, and 1 experienced clinical progression. Thirty-five patients were still receiving treatment at the time of data cutoff.

Of the 54 patients who received single-agent camrelizumab, 53 received treatment and 42 patients discontinued by data cutoff; 11 patients were still receiving treatment. Of the 35 patients in the chemotherapy arm, 30 received treatment and all patients discontinued.

Across the 3 arms, the median age was 51.7 years (range, 25.0-73.0). Most patients in the doublet, monotherapy, and chemotherapy arms had an ECOG performance status of 1 (63.8%; 66.7%; 65.7%), squamous carcinoma (77.1%; 75.9%; 82.9%), and PD-L1 positivity (61.9%; 63.0%; 71.4%). More than half of patients had more than 1 metastatic site (55.2%; 51.9%; 77.1%).

In the doublet arm, 61.9% of patients previously underwent radical surgery, 31.4% had received prior radical concurrent chemoradiation, and 88.6% had prior radical treatment; in the monotherapy arm, these rates were 57.4%, 37.0%, and 85.2%, respectively, and these rates were 45.7%, 40.0%, and 74.3%, respectively, in the chemotherapy arm. The majority of patients spanning the 3 arms received 1 prior line of systemic treatment (81.0%; 74.1%; 74.3%), and the remainder had received 2 prior lines. All patients had prior exposure to platinum-based chemotherapy. Targeted therapy was previously received by 26.7% of those in the doublet arm, 38.9% of those in the monotherapy arm, and 34.3% of those in the chemotherapy arm.

Additional efficacy data indicated that the median TTR by BICR with camrelizumab plus famitinib was 2.1 months (range, 1.5-6.2), the median DOR was 16.0 months (95% CI, 6.3-16.0), and the DOR rate at 6 months was 76.0% (95% CI, 58.8%-86.7%). With single-agent camrelizumab, the median TTR by BICR was also 2.1 months (range, 1.4-12.5), the median DOR was NR (95% CI, 4.1-NR), and the 6-month DOR rate was 80.8% (95% CI, 42.4%-94.9%).

The median PFS by BICR with the doublet was longer than that observed with the monotherapy, at 7.2 months (95% CI, 6.1-12.4) vs 4.0 months (95% CI, 2.1-6.14), respectively (HR, 0.5; 95% CI, 0.4-0.8; P = .0021). The median OS was 20.0 months (95% CI, 15.6-NR) with the doublet vs NR (95% CI, 12.3-NR) with the monotherapy (HR, 0.7; 95% CI, 0.4-1.4; P = .1563); the median OS was 15.8 months (95% CI, 8.7-19.9) with chemotherapy. The 6-month OS rates in the doublet, monotherapy, and chemotherapy arms, respectively, were 90.5% (95% CI, 83.0%-94.8%), 86.5% (95% CI, 73.8%-93.3%), and 75.4% (95% CI, 56.8%-86.9%), respectively.

Regarding safety, treatment-related AEs (TRAEs) occurred in all patients who received camrelizumab plus famitinib, 94.3% of those given the monotherapy, and all patients who received chemotherapy. In the doublet arm, these effects were related to camrelizumab in 99.0% of patients and related to famitinib in all patients; in the monotherapy arm, 94.3% of the effects were related to camrelizumab.

Grade 3 or higher TRAEs occurred in 84.8% of those given the combination, 15.1% of those given the monotherapy, and 60.0% of those given the chemotherapy. Serious TRAEs were experienced by 38.1%, 15.1%, and 16.7% of patients, respectively. Immune-related TRAEs were observed in 50.5% of those given camrelizumab plus famitinib and 69.8% of those given camrelizumab alone.

In the doublet arm, TRAEs led to camrelizumab interruption for 58.1% of patients, famitinib interruption for 64.8% of patients, and famitinib dose reduction for 55.2% of patients. In this group, TRAEs led to discontinuation of camrelizumab for 1.9% of patients and discontinuation of famitinib for 16.2% of patients. In the monotherapy arm, TRAEs resulted in interruption of camrelizumab for 20.8% of patients. TREAEs led to discontinuation of camrelizumab for 3.8% of patients. Two patients on the doublet arm experienced TRAEs that resulted in death.

The most common TRAEs experienced in the doublet, monotherapy, and chemotherapy arms, respectively, included decreased white blood count (78.1%; 20.8%; 80.0%), decreased neutrophil count (69.5%; 7.5%; 56.7%), anemia (67.6%; 32.1%; 66.7%), proteinuria (64.8%; 3.8%; 6.7%), decreased platelet count (62.9%; 13.2%; 26.7%), hypertension (51.4%; 0%; 0%), hypothyroidism (43.8%; 20.8%; 3.3%), diarrhea (35.2%; 3.8%; 13.3%), hypertriglyceridemia (31.4%; 22.6%; 3.3%), increased aspartate aminotransferase (30.5%; 24.5%; 13.3%), Palmar-plantar erythrodysesthesia (28.6%; 0%; 0%), increased alanine aminotransferase (26.7%; 26.4%; 16.7%), urinary tract infection (22.9%; 9.4%; 6.7%), hypercholesterolemia (21.9%; 15.1%; 6.7%), reduced lymphocyte count (21.9%; 15.1%; 20.0%), weight decrease (21.0%; 5.7%; 10.0%), occult blood positivity (20.0%; 9.4%; 10.0%), reduced appetite (20.0%; 7.5%; 30.0%), reactive capillary endothelial proliferation (20.0%; 64.2%; 0%), asthenia (17.1%; 7.5%; 20.0%), nausea (7.6%; 5.7%; 30.0%), and hypoesthesia (1.0%; 1.8%; 20.0%).

“Toxicities were consistent with previous reports of camrelizumab and famitinib,” Wu concluded. “No new safety signals were identified.”

Editor’s Note: Dr Wu did not disclose any conflicts of interests.

References

1. Wu X, Xia L, Zhang K, et al. LBA44 camrelizumab plus famitinib versus camrelizumab alone and investigator’s choice of chemotherapy in women with recurrent or metastatic cervical cancer. Ann Oncol. 2023;34(suppl 2):S1284-S1285. doi:10.1016/j.annonc.2023.10.038
2. Xia L, Zhou Q, Gao Y, et al. A multicenter phase 2 trial of camrelizumab plus famitinib for women with recurrent or metastatic cervical squamous cell carcinoma. Nat Commun. 2022;13(1):7581. doi:10.1038/s41467-022-35133-4