Background Ropeginterferon alfa-2b is a novel mono-pegylated interferon that has only one major form as opposed to 8–14 isomers of other on-market pegylated interferon, allowing injection every two or more weeks with higher tolerability. It received European Medicines Agency and Taiwan marketing authorization in 2019 and 2020, for treatment of polycythemia vera. This phase I/II study aimed to have preliminary evaluation of safety and efficacy in chronic hepatitis B. Methods Thirty-one HBeAg-positive and 31 HBeAg-negative were stratified by HBeAg status and randomized at 1:1:1 ratio to q2w ropeginterferon alfa-2b 350 μg (group 1), q2w 450 μg (group 2) or q1w PEG-IFN alfa-2a 180 μg (group 3). Each patient received 48-week treatment (TW48) and 24-week post-treatment follow-up (FW24). Results The baseline demographics were comparable among the three groups, except for mean HBeAg in HBeAg-positive patients (2.90, 2.23, 2.99 log10 S/CO, respectively). Cumulative HBeAg seroconversion rate at follow-up period was 27.3% (3/11), 36.4% (4/11), and 11.1% (1/9) with time to HBeAg seroconversion starting from TW24, TW16, and TW48 in group 1, 2, and 3, respectively. The rate of HBV DNA < 2000 IU/mL and HBsAg levels < 1500 IU/mL at FW24 were comparable in all groups. Ropeginterferon alfa-2b (group 1 & 2) had numerically lower incidence of rash (9.5% and 4.5%) as compared to PEG-IFN alfa-2a (36.8%). Ropeginterferon alfa-2b 350 μg (group 1) had more ALT elevation (38.1%), however the rate was comparable in group 2 (9.1%) and group 3 (10.5%). Conclusion In this preliminary study, ropeginterferon alfa-2b, although in only half the number of injections, is as safe and effective as pegylated interferon alfa-2a for chronic hepatitis B. Graphic abstract

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Background and Aim Ropeginterferon alfa‐2b (P1101) is a novel long‐acting mono‐PEGylated recombinant proline interferon (IFN) conjugated to a 40 kDa branched polyethylene glycol (PEG) chain at its N‐terminus, allowing every‐two‐week injection. It received European Medicines Agency and Taiwan marketing authorization for the treatment of polycythemia vera in 2019 and 2020, respectively. This phase 2 study aimed to evaluate the pharmacokinetics, safety, and preliminary efficacy of ropeginterferon alfa‐2b as compared with PEG‐IFN‐α2a in patients with chronic hepatitis C virus genotype 1 infection. Methods One hundred six treatment naive patients were enrolled in this phase 2 study and randomized to four treatment groups: subcutaneous weekly PEG‐IFN‐α2a 180 μg (group 1), weekly ropeginterferon alfa‐2b 180 μg (group 2), weekly ropeginterferon alfa‐2b 270 μg (group 3), or biweekly ropeginterferon alfa‐2b 450 μg (group 4) plus ribavirin for 48 weeks. Results After multiple weekly administration, serum exposure (AUC0‐τ) in ropeginterferon alfa‐2b 180 μg was approximately 41% greater and the accumulation ratio of 2‐fold greater than PEG‐IFN‐α2a 180 μg. The incidences of flu‐like symptoms were 66.7% (18/27), 53.3% (16/30), 55.0% (11/20), and 48.3% (14/29), anxiety were 14.8% (4/27), 6.7% (2/30), 0%, and 0%, and depression were 25.9% (7/27), 13.3% (4/30), 0%, and 3.4% (1/29), for groups 1–4, respectively. Two grade 2 of 3 depression were noted in PEG‐IFN‐α2a arm, but none in ropeginterferon arms. The SVR24 rates were 77.8% (21/27), 66.7% (20/30), 80% (16/20), and 69% (20/29), respectively. Conclusions Ropeginterferon alfa‐2b showed longer effective half‐life and superior safety profile than PEG‐IFN‐α2a. Biweekly injection of ropeginterferon alfa‐2b will be studied in larger viral hepatitis patient population.

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We aimed to evaluate its safety, pharmacokinetics (PK) and pharmacodynamics (PD).Methods: Thirty-six subjects received single subcutaneous injection of ropeginterferon alfa-2b at doses ranging from 24 to 270 μg, and 12 subjects received pegylated IFN alfa-2a subcutaneously at 180 μg. Primary endpoints were safety/PK profiles of ropeginterferon alfa-2b, while secondary endpoints were to compare PK/PD parameters with pegylated IFN alfa-2a.Results: Adverse events in ropeginterferon alfa-2b and pegylated IFN alfa-2a groups were similar, and most of them were mild or moderate. Mean C max increased from 1.78 to 24.84 ng/mL along with the dose escalations in ropeginterferon alfa-2b groups and was 12.95 ng/mL for pegylated IFN alfa-2a. At 180 μg, ropeginterferon alfa-2b showed statistically significant C max geometric mean ratio (1.76; P = .0275).Mean T max ranged from 74.52 to 115.69 h for ropeginterferon alfa-2b groups, and was 84.25 h for pegylated IFN alfa-2a. Mean AUC 0-t increased from 372.3 to 6258 ng•h/mL with the dose escalations in the ropeginterferon alfa-2b groups, while for pegylated IFN alfa-2a it was found to be 2706 ng•h/mL in pegylated IFN alfa-2a.For neopterin and 2 0 ,5 0 -oligoadenylate synthase, mean E max , T max and AUC 0-t of ropeginterferon alfa-2b were similar to those of pegylated IFNα-2a at 180 μg. Conclusion:Ropeginterferon alfa-2b up to 270 μg was safe and well tolerated. The PK/PD parameters of ropeginterferon alfa-2b showed increase in dose-response. Ropeginterferon alfa-2b had higher drug exposures and showed similar safety profile when compared to pegylated IFN alfa-2a at the same dose level.

Patients diagnosed with high-risk essential thrombocythemia (ET) have limited treatment options to reduce the risk of thrombosis and lessen the progression of the disease by targeting the molecular source. Hydroxyurea is the recommended treatment, but many patients experience resistance or intolerance. Anagrelide is an approved second-line option for ET, but concerns of a higher frequency of disease transformation may affect its role as a suitable long-term option. Interferons have been evaluated in myeloproliferative neoplasms for over 30 years, but early formulations had safety and tolerability issues. SURPASS-ET (NCT04285086) is a phase III, open-label, multicenter, global, randomized, active-controlled trial that will evaluate the safety, efficacy, tolerability and pharmacokinetics of ropeginterferon alfa-2b compared with anagrelide as second-line therapy in high-risk ET.

Background: MCC is a neuroendocrine cancer of the skin that predominantly occurs in older individuals of northern European ancestry. While localized disease can often be treated with surgery and radiation therapy, there is a need for effective, well-tolerated chemotherapeutic options for patients with progressive or metastatic disease. Among patients with metastatic MCC, overall 5-year survival rate is 11% and median survival is in the range of 7 to 9 months. To date, no chemotherapeutic agent has been able to demonstrate a significant improvement in survival. Toxicity also is a major concern with these older patients. IMGN901 is a novel CD56-targeting anticancer agent. CD56 is expressed on virtually all MCC tumors. IMGN901 consists of a potent maytansinoid cytotoxic agent, DM1, attached to a CD56-binding monoclonal antibody, huN901, using an engineered linker. Once bound to CD56, IMGN901 is internalized into the cancer cell and the DM1 is released to kill the cell via inhibition of the polymerization of tubulin. Objective: Study 002 is an ongoing phase I trial established to determine the maximum tolerated dose (MTD), pharmacokinetics (PK) and activity of IMGN901 in patients with CD56-expressing solid tumors, including patients with MCC. Methods: IMGN901 is administered intravenously as monotherapy daily for 3 consecutive days every 3 weeks. Results: Six patients with MCC have been enrolled in Study 002 in addition to patients with other types of CD56+ solid tumors. Clinical benefit has been observed in 3 of these 6 patients including one complete response (CR), one partial response (PR) and one stable disease (SD). The patient who experienced a CR has remained disease free for more than 4 years. The patient who experienced a PR received 1 cycle of IMGN901 treatment, but had a serious adverse event and declined further treatment. This patient had sustained clinical benefit for more than 5 months, including additional tumor shrinkage. The patient who experienced SD entered Study 002 with bone metastases and had received 3 prior therapies. This patient had SD lasting approximately 3 months. Overall, a clinical benefit rate (CR+PR+SD) of 50% has been observed. The 6 MCC patients received IMGN901 at doses ranging from 36 to 75 mg/m2/day. The MTD of IMGN901 has not been defined in Study 002 and a dose level of 94 mg/m2/day will be evaluated next. Earlier this year, we reported pooled data from two studies in CD56+ solid tumors summarizing the encouraging experience with IMGN901 for the treatment of small-cell lung cancer (SCLC). SCLC and MCC have shared morphologic characteristics and a common clinical course. Conclusion: There are encouraging findings to date with IMGN901 for the treatment of MCC. The findings are supportive of the initial findings with the compound for the treatment of SCLC and vice versa. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B237.