Frontline SHR-1701 Plus BP102 and Chemo Shows Potent Activity in Cervical Cancer

The novel bifunctional fusion protein SHR-1701 combined with standard first-line treatment with the bevacizumab (Avastin) biosimilar BP102 and platinum-doublet chemotherapy produced high, durable responses and was deemed tolerable in patients with cervical cancer, according to data from the phase 1b portion of an ongoing phase 1b/3 trial (NCT05179239).¹

Findings presented at the2023 ASCO Annual Meeting showed that patients who received the combination (n = 31) achieved an overall response rate (ORR) of 77.4% (95% CI, 58.9%-90.4%); this consisted of 4 complete responses and 20 partial responses. Five patients achieved stable disease and 2 patients experienced disease progression.

The disease control rate (DCR) was 93.5% (95% CI, 78.6%-99.2%), as was the 6-month progression-free survival (PFS) rate (95% CI, 76.6%-98.3%). Notably, 96.8% of patients achieved shrinkage in target lesions from baseline. All responses are ongoing.

“SHR-1701 plus platinum-based doublet chemotherapy and BP102 provided a manageable safety profile and potent antitumor activity [to] patients with persistent, recurrent, or metastatic cervical cancer,” lead study author Jihong Liu, MD, of Sun Yat-sen University Cancer Center, Guangzhou, China, and colleagues, wrote in a poster of the data.

The PD-L1 and TGFβ receptor II inhibitor SHR-1701 has previously shown promising activity and manageable safety for patients with cervical cancer who progressed on a platinum-based regimen (n = 32) in a phase 1 study (NCT03774979).2 SHR-1701 elicited an ORR of 15.6% (95% CI, 5.3%-32.8%), with a DCR of 50% (95% CI, 31.9%-68.1%). The median PFS was 2.7 months (95% CI, 1.4-4.1), and the 12-month overall survival rate was 54.6% (95% CI, 31.8%-72.7%).²

At the 2023 ASCO Annual Meeting, investigators presented initial efficacy and safety results from their investigation of SHR-1701, BP102, and chemotherapy as a first-line approach for patients with cervical cancer regardless of PD-L1 expression.¹ The data cutoff date for the analysis was December 16, 2022.

The multicenter study consisted of a safety run-in (part 1) and a cohort expansion portion (part 2). The study enrolled patients between the ages of 18 and 75 years with persistent, recurrent, or metastatic cervical cancer. Patients must not have had prior exposure to systemic therapy or be amenable to curative treatment. Notably prior chemoradiotherapy was allowed if patients experienced disease recurrence, provided single-agent chemotherapy was administered as a sensitizer. Other key inclusion criteria included having an ECOG performance status of 0 or 1, measurable disease according to RECIST v1.1 criteria, a life expectancy of 12 weeks or more, and adequate organ function.

In the phase 1b portion of the study, patients in the experimental arm were given 30 mg/kg of SHR-1701 plus a standard 15-mg/kg dose of BP102, 175 mg/m2 of paclitaxel, and either 50 mg/m2 of cisplatin or carboplatin at area under the curve 5.

The primary end points were safety and ORR per RECIST v1.1 criteria.

A total of 31 patients were enrolled onto the expansion cohort from February 26, 2022 to August 12, 2022. The median age in this patient population was 55 years (range, 27-71). Regarding ECOG performance status, 67.7% had a status of 0 and 32.3% had a status of 1. Most patients (61.3%) had persistent or recurrent disease with distant metastases, 22.6% had metastatic disease, and 16.1% had persistent or recurrent disease without distant metastases.

Therapeutic approaches previously administered to patients included chemoradiotherapy alone (41.9%), surgery plus chemoradiotherapy (16.1%), radiotherapy and surgery (9.7%), surgery alone (6.5%), or chemotherapy alone (3.2%). Moreover, 22.6% of patients did not receive prior therapy.

At a median follow-up of 7.2 months (range, 4.2-9.3), 6 patients had discontinued study agents due to disease progression (n = 2), withdrawal of consent (n = 2), adverse effects (AEs; n = 1) and investigator decision (n = 1).

The median duration of exposure to SHR-1701, paclitaxel, BP102, and cisplatin or carboplatin was 6.5 months (range, 1.4-9.3), 4.4 months (2.1-8.3), 5.7 months (2.8-9.3), and 4.6 months (2.1-6.8) and 4.4 months (2.3-6.8), respectively.

Treatment-related AEs (TRAEs) led to discontinuation of any study drug in 38.7% of patients. Specifically, 12.9% of patients discontinued SHR-1701 due to the following TRAEs: infusion-related reactions, immune-mediated dermatitis, increased alanine and aspartate transaminase (ALT; AST), and decreased platelet count. Five patients (16.1%) experienced an immune-related AE. No treatment-related deaths occurred.

Moreover, 83.9% of patients experienced grade 3 or higher TRAEs, the most common of which were decreased neutrophil count (58.1%), decreased white blood cell count (41.9%), and anemia (25.8%).

Common any-grade TRAEs occurring in 30% or more of patients included anemia (90.3%), neutrophil count decrease (80.6%), white blood cell decrease (77.4%), platelet count decrease (58.1%), vomiting (54.8%), rash (45.2%), hypoesthesia (41.9%), alopecia (41.9%), lymphocyte count decrease (38.7%), nausea (38.7%), decreased appetite (38.7%), asthenia (35.5%), blood creatine increase (35.5%), AST increase (32.3%), hypothyroidism (32.3%), and diarrhea (32.3%).

The investigators concluded that results from the phase 1b study support the continued investigation of SHR-1701 in the randomized, placebo-controlled phase 3 portion of this trial.

References

1. Liu J, Zhou Y, Wang Y, et al. SHR-1701 in combination with platinum-based chemotherapy and BP102 (a bevacizumab biosimilar) for persistent, recurrent, or metastatic cervical cancer: data from a phase 1b/3 study. J Clin Oncol. 2023;41(suppl 16):5529. doi:10.1200/JCO.2023.41.16_suppl.5529
2. Feng J, Tang D, Wang J, et al. SHR-1701, a bifunctional fusion protein targeting PD-L1 and TGFβ, for recurrent or metastatic cervical cancer: a clinical expansion cohort of a phase 1 study. Clin Cancer Res. 2022;28(24):5297-5305. doi:10.1158/1078-0432.CCR-22-0346