The news widespread in the industry that Hengrui has received the pharmaceutical product registration approval for its anti-PD-1 camrelizumab has been confirmed recently. It took 24 days from the beginning of review to the receipt of approval on May 29.

Camrelizumab (R&D code: SHR-1210, trade name: Ailituo) is approved as a third-line therapy for the relapsed/refractory classical Hodgkin lymphoma (R/R cHL) this time, which is the second Chinese-produced anti-PD-1 monoclonal antibody drug approved for this indication following Innovent’s Tyvyt (sintilimab, approved for marketing by the National Medical Products Administration on Dec. 27, 2018, used to treat R/R cHL patients who have received at least second-line systematic chemotherapies) and the fifth anti-PD-1 monoclonal antibody drug approved for marketing in the Chinese market. With this, there is a new choice in the therapeutic area of R/R cHL.

Let’s first learn about what R/R cHL is.

Hodgkin’s lymphoma (HL) is a kind of malignant tumor originating in the lymphohematopoietic system, which mainly occurs in children and youth, with the morbidity accounting for 15%~25% of all lymphomas and generally with a good prognosis. More than 80% classical Hodgkin lymphomas (cHL) can be cured after first-line therapies, and even for patients with R/R cHL, about 50% of them can be cured with high-dose chemotherapies in combination with autologous stem cell transplantation (ASCT).

However, it’s difficult for R/R cHL patients who relapse after receiving ASCT or are not suitable for ASCT or hematopoietic stem cell transplantation (HSCT) to reach complete remission or long-term survival due to the limited treatment choices. The 9p24.1 cytogenetic abnormalities of cHL cells result in overexpression of PD-1 ligands: PD-L1 and PD-L2, which provides the theoretical basis for the PD-1/PD-L1 inhibitor treatment.

As a humanized anti-PD-1 IgG4 monoclonal antibody, camrelizumab has a high affinity with human PD-1 and has demonstrated good anti-tumor efficacy in the preclinical study.

Hengrui Medicine released clinical data of efficacy of camrelizumab in treating R/R cHL at the 21^st annual meeting of the CSCO (Chinese Society of Clinical Oncology) last year.

The study recruited 75 R/R cHL patients aged above 18, and all the patients were R/R cHL patients who relapsed after receiving ASCT or who received ≥2-line systemic chemotherapies and were not suitable to receive stem cell transplantation. They received camrelizumab 200mg q2w until there was a disease progression or intolerable toxicity.

The results by Mar. 18, 2018 (6 months after the last subject was enrolled) showed that camrelizumab demonstrated positive effectiveness and safety in treating R/R cHL, wherein, the objective response rate (ORR) reached 84.8% and complete response (CR) reached 30.3%. The significant reduction of the target lesion tumor load of patients could be observed during the study.

In terms of safety, camrelizumab monotherapy showed good safety in treating R/R cHL patients, with tolerable adverse reactions. Except the reactive skin capillary hyperplasia, other common adverse events were comparable to similar products, and the reactive skin capillary hyperplasia had mild symptoms and automatically regressed about half a year later.

Let’s see the efficacy of other anti-PD-1 monoclonal antibodies in R/R cHL. And if you want to know more about pharma industry, Pharmasource, a professional platform where thousands of health care products suppliers gathered, could help you.

Nivolumab

Nivolumab is a humanized anti-PD-1 monoclonal antibody and the first immune checkpoint inhibitor approved by the FDA to treat R/R cHL, of which the effectiveness was first proved in the Phase I clinical trial CheckMate 039. Among the 23 R/R cHL patients, 78% failed the antibody-drug conjugate BV (Brentuximab vedotin) treatment and 78% patients progressed after receiving ASCT; in the treatment with nivolumab, the overall response rate reached 87%, complete response reached 17%, and six-month progression-free survival reached 86%.

The multicenter Phase II clinical trial CheckMate 205 further verified the above results. 80 R/R cHL patients in cohort B received nivolumab, who relapsed after receiving ASCT and then failed BV treatment; the ORR reached 66.3%, CR reached 9%, median time to response was 2.1 months, median duration of remission was 7.8 months, and median PFS was 10 months up to 1 year of drug use. Based on results of the above two studies, nivolumab was approved for marketing by FDA in May 2016 for R/R cHL patients who have relapsed after receiving ASCT or failed BV treatment.

Pembrolizumab

Pembrolizumab is another humanized anti-PD-1 monoclonal antibody with efficacy against R/R cHL similar to that of nivolumab and is the second immune checkpoint inhibitor approved by FDA to treat R/R cHL following nivolumab. Its KEYNOTE-087 study recruited 210 cHL patients who relapsed after receiving ASCT and (or) failed BV treatment; in the treatment with pembrolizumab, the ORR was 69%, CR was 22.4%, nine-month PFS was 63.4%, and OS was 97.5%.

Tislelizumab

The NDA of tislelizumab was filed based on clinical and non-clinical data, including the results of the pivotal Phase 2 clinical study treating Chinese R/R cHL patients. The Phase 2 study recruited 70 patients. The results showed that at the time of the data cutoff with a minimum of 24 weeks of follow-up and a median follow-up time of 7.85 months, the overall response rate was 85.7%, including 61.4% complete response. The occurrence frequency and severity of adverse events were overall consistent with the safety and tolerance data of Phase 1 clinical study of tislelizumab reported earlier.

Sintilimab

ORIENT-1 is a multicenter, single-arm, Phase II clinical study conducted in China, with patients recruited of cHL patients who failed ≥2 courses of systemic therapy (including autologous hematopoietic stem cell transplantation (HSCT)). They were given 200mg intravenous injection of sintilimab every 3 weeks, until disease progression, death, unacceptable toxicity, or withdrawal from study.

96 enrolled patients received treatment. As of the data cutoff on Oct. 16, 2018, 72.9% of patients were continuing treatment with a median follow-up of 14 months. Median number of treatment cycles was 20 (range: 1 to 26). Overall response rate was 85.4% based on IRRC review. 29.2% patients achieved complete response. 59 out of 82 patients who had achieved complete or partial response continued to have an on-going response. The median duration of response (DoR) and progression-free survival (PFS) have not been reached.

From the perspective of current data, camrelizumab is full of therapeutic potential in the R/R cHL area; camrelizumab is not inferior in any respect to similar drugs. And the clinical study of camrelizumab in treating advanced hepatocellular carcinoma has also made fruitful achievements. We’re excited to see camrelizumab bring better survival benefits and clinical significance to tumor patients in the future.

References:

1. Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma[J]. N Engl J Med, 2015, 372(4):311-319.

2. Ansell S, Armand P, Timmerman JM, et al. Nivolumab in patients (pts) with relapsed or refractory classical Hodgkin lymphoma (R/R cHL): clinical outcomes from extended follow- up of a phase 1 study (CA209-039).

3. Younes A, Santoro A, Shipp M, et al. Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem- cell transplantation and brentuximab vedotin: a multicentre, multicohort, singlearm phase 2 trial[J]. Lancet Oncol, 2016, 17(9):1283-1294.

4. Yuankai Shi, Hang Su, Yongping Song, et al. Safety and activity of sintilimab in patients with relapsed or refractory classical Hodgkin lymphoma (ORIENT-1): a multicentre, single-arm, phase 2 trial. Lancet Haematology. Jan 2019.

About  the Author:    

Yefenghong

Ye  Fenghong, a medical editor specializing in oncology at a healthcare internet  company, has conducted in-depth research on the pathogenesis and clinical  treatment of lung cancer and breast cancer. She has previously been involved  in the design and synthesis of anti-tumor drugs and has some experience in  computer-aided drug design. She is currently devoted to introducing  cutting-edge cancer treatment drugs to a wide range of readers, aiming to  help more people avoid cancer pain and embrace good health.    

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