First-Line Camrelizumab Findings Reveal Robust and Durable Responses in Advanced Squamous NSCLC

First-line treatment with camrelizumab, an investigational PD-1 inhibitor, plus chemotherapy elicited robust and durable clinical responses in patients with advanced squamous non–small cell lung cancer (NSCLC), according to findings from the phase 3 CameL-sq trial (NCT03668496) presented during the European Lung Cancer Virtual Congress 2021.¹

The median progression-free survival (PFS) was 8.5 months (95% CI, 6.9-10.4) with camrelizumab plus chemotherapy compared with 4.9 months (95% CI, 4.2-5.5) with placebo plus chemotherapy per a blinded independent review committee (BIRC; HR, 0.37; 95% CI, 0.29-0.47; P < .0001), meeting the primary end point of the study (TABLE¹).

Moreover, PFS by BIRC favored the camrel- izumab-based regimen vs the placebo-based regimen irrespective of age, sex, ECOG performance status (PS), smoking history, disease stage, presence of liver or brain metastases at enrollment, and PD-L1 status by tumor proportion score (TPS).

“These findings support camrelizumab plus paclitaxel and carboplatin as standard first-line treatment for [patients with] advanced squamous non–small cell lung cancer,” said Caicun Zhou, MD, PhD, lead study author and director of the Department of Oncology at Shanghai Pulmonary Hospital in China, in a virtual presentation of the data.

As monotherapy, camrelizumab has shown antitumor activity in patients with previously treated advanced NSCLC. Additionally, interim f indings from the phase 3 CameL trial showed that at a median follow-up of 11.9 months, the median PFS was 11.3 months with camrelizumab plus chemotherapy vs 8.3 months with placebo plus chemotherapy in patients with chemotherapy-naïve advanced nonsquamous NSCLC (HR, 0.60; 95% CI, 0.45-0.79; P = .0001).²

The findings from the CameL trial established camrelizumab plus chemotherapy as a standard frontline option for Chinese patients with advanced nonsquamous NSCLC who do not harbor EGFR mutations or ALK translocations, Zhou explained.

The CameL-sq study aimed to establish camrelizumab as a standard frontline option for patients with advanced squamous cell disease.

In the study, 390 patients were randomized 1:1 to the camrelizumab- or placebo-based regimens. Patients in the camrelizumab group (n = 193) received 200 mg of camrelizumab plus carboplatin and 175 mg/m2 of paclitaxel in 3-week cycles for 4 to 6 cycles followed by 200 mg of camrelizumab given every 3 weeks until progressive disease or unacceptable toxicity.

In the placebo group, 197 patients were allocated and 196 received placebo plus carboplatin and paclitaxel at the same dose as the camrelizumab group, followed by placebo until disease progression or unacceptable toxicity. Patients receiving placebo could cross over to 200 mg of camrelizumab if they experienced progressive disease with placebo per BIRC.

Eligible patients had pathologically confirmed stage IIIB to IV squamous NSCLC, no prior systemic treatment, and an ECOG PS of 0 or 1.

Patients were stratified by sex, smoking history (≥ 400 cigarette pack-years vs < 400 cigarette pack-years vs never-smokers), and the presence of liver or brain metastases at enrollment (both sites vs 1 site vs none).

PFS per BIRC served as the study’s primary end point, with overall survival (OS), overall response rate (ORR), duration of response (DOR), disease control rate (DCR), and safety as key secondary end points.

Of the patients in the camrelizumab group, 126 discontinued treatment because of disease progression (n = 77), adverse effects (AEs; n = 23), withdrawn consent (n = 14), death (n = 6), investigator decision (n = 4), and other reasons (n = 2); 67 patients are receiving ongoing treatment. In the placebo group, 186 patients discontinued treatment because of disease progression (n = 161), withdrawn consent (n = 11), AEs (n = 5), death (n = 5), lost to follow-up (n = 1), investigator decision (n = 1), new antitumor therapy (n = 1), and other reasons (n = 1); 10 patients are receiving ongoing treatment.

Baseline patient characteristics were well- balanced between arms. The median patient age was 64 years in the camrelizumab arm vs 62 years in the placebo arm, and the majority of patients were male in both arms. Most patients were smokers, had an ECOG PS of 1, and had stage IV disease.

Additionally, 13.0% of patients receiving camrelizumab had liver or brain metastases upon enrollment compared with 11.2% of patients receiving placebo.

In the camrelizumab arm, 47.2% of patients had less than 1% PD-L1 TPS expression, 49.2% of patients had greater than 1% PD-L1 TPS expression, and 3.6% were not evaluable. These rates were 49.5%, 47.4%, and 3.1%, respectively, in the placebo arm.

Secondary end point analyses revealed that the median OS was not reached (NR) with camrelizumab/chemotherapy (95% CI, 18.4-NR) compared with 14.5 months (95% CI, 13.2-16.6) with placebo/chemotherapy (HR, 0.55; 95% CI, 0.40-0.75; P < .0001).

In all subgroups except female patients (HR, 1.06; 95% CI, 0.21-5.26), median OS favored the camrelizumab regimen compared with the placebo regimen.

The ORR by BIRC was 64.8% (95% CI, 57.6%71.5%) with camrelizumab/chemotherapy vs 36.7% (95% CI, 30.0%-43.9%) with placebo/ chemotherapy. In the experimental arm, 7.8% of patients achieved a complete response (CR), 57.0% achieved a partial response (PR), 23.3% had stable disease (SD), 7.8% had progressive disease, and 4.1% were not evaluable. In the placebo arm, 1.5% of patients achieved a CR, 35.2% achieved a PR, 46.4% had SD, 14.8% had progressive disease, and 2.0% were not evaluable.

The DCR was 88.1% with the addition of camrelizumab (95% CI, 82.7%-92.3%) vs 83.2% with placebo (95% CI, 77.2%-88.1%). The median DOR was 13.1 months (95% CI, 9.3-15.7) vs 4.4 months (95% CI, 4.2-4.9), respectively.

Patients received camrelizumab for a median of 12 cycles (range, 1-32) and placebo for median of 7 cycles (range, 1-26). In both arms, patients received a median of 5 cycles (range, 1-6) of paclitaxel and carboplatin.

All patients (100%) on the camrelizumab regimen vs 99.5% of patients on the placebo regimen experienced any-grade treatment-emergent AEs (TEAEs); 80.3% vs 75.0% of patients reported grade 3 or 4 TEAEs, respectively. Additionally, 10.4% of patients in the camrelizumab group died from TEAEs compared with 13.8% of patients in the placebo group.

Similarly, all patients (100%) on the camrelizumab regimen vs 99.5% of patients on the placebo regimen experienced any-grade treatment-related AEs (TRAEs); 73.6% vs 71.4% of patients reported grade 3 or 4 TRAEs, respectively. Additionally, 3.1% of patients receiving camrelizumab died from TRAEs compared with 1.5% of patients who received placebo.

Immune-related AEs (irAEs) were reported in 76.7% of patients on camrelizumab compared with 20.4% of patients on placebo.

Common TRAEs included hematologic events, such as decreased white blood cell, neutrophil and platelet counts, and anemia; and nonhematologic events, such as alopecia, hypoesthesia, asthenia, decreased appetite, nausea, increased alanine aminotransferase and aspartate aminotransferase, and extremity pain.

_REFERENCES

_{1. Zhou C, Ren S, Chen J, et al. Camrelizumab or placebo plus carboplatin and paclitaxel as first-line treatment for advanced squamous NSCLC (CameL-sq): a randomized, double-blind, multicenter, phase 3 trial. J Thorac Oncology. 2021;16(4):S748. doi:10.1016/S1556-0864(21)01938-9}

_{2. Zhou C, Chen G, Huang Y, et al. Camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in chemotherapy-naive patients with advanced non-squamous non-small-cell lung cancer (CameL): a randomised, open-label, multicentre, phase 3 trial. Lancet Respir Med. 2021;9(3):305-314. doi:10.1016/S2213-2600(20)30365-9}