Cemiplimab-Rwlc + Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer

The FDA approved cemiplimab-rwlc in combination with platinum-based chemotherapy for adult patients with advanced non-small cell lung cancer (NSCLC) with no EGFR, ALK, or ROS1 aberrations. Efficacy was evaluated in Study 16113 (NCT03409614), a randomized, multicenter, multinational, double-blind, active-controlled trial in 466 patients with advanced NSCLC who had not received prior systemic treatment.

FDA; cancer research; clinical trials. FDA; cancer research; clinical trials

Patients were randomized (2:1) to either cemiplimab-rwlc plus platinum-based chemotherapy every 3 weeks for 4 cycles followed by cemiplimab-rwlc and maintenance chemotherapy or placebo plus platinum-based chemotherapy every 3 weeks for 4 cycles followed by placebo and maintenance chemotherapy. The main efficacy outcome measure was overall survival (OS). Additional efficacy outcome measures were progression-free survival (PFS) and overall response rate (ORR) as assessed by blinded independent central review (BICR).

Cemiplimab-rwlc plus platinum-based chemotherapy demonstrated a statistically significant and clinically meaningful improvement in OS compared to placebo plus chemotherapy (HR=0.71 [95% CI: 0.53, 0.93], two-sided p=0.0140). Median OS was 21.9 months (95% CI: 15.5, not evaluable) in the cemiplimab-rwlc plus chemotherapy arm and 13.0 months (95% CI: 11.9, 16.1) in the placebo plus chemotherapy arm. Median PFS per BICR was 8.2 months (95% CI: 6.4, 9.3) in the cemiplimab-rwlc plus chemotherapy arm and 5.0 months (95% CI: 4.3, 6.2) in the placebo plus chemotherapy arm (HR 0.56; 95% CI: 0.44, 0.70, p<0.0001). Confirmed ORR per BICR was 43 percent (95% CI: 38, 49) and 23 percent (95% CI: 16, 30) in the respective treatments.

The most common (>=15%) adverse reactions were alopecia, musculoskeletal pain, nausea, fatigue, peripheral neuropathy, and decreased appetite. The recommended cemiplimab-rwlc dose is 350 mg IV every 3 weeks. Refer to the prescribing information for the agents administered in combination with cemiplimab-rwlc for recommended dosing information, as appropriate.

Brentuximab Vedotin + Chemotherapy for Pediatric Patients With Classical Hodgkin Lymphoma

The FDA has approved brentuximab vedotin in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide for pediatric patients 2 years of age and older with previously untreated high-risk classical Hodgkin lymphoma. This is the first pediatric approval for brentuximab vedotin.

Efficacy was evaluated in a randomized, open-label, actively controlled trial. High risk was identified as Ann Arbor Stage IIB with bulk disease, Stage IIIB, Stage IVA, and Stage IVB. Of the 600 total patients randomized, 300 were randomized to brentuximab vedotin plus doxorubicin (A), vincristine (V), etoposide (E), prednisone (P), and cyclophosphamide (C) [brentuximab vedotin + AVEPC], and 300 patients were randomized to A+bleomycin (B)+V+E+P+C [ABVE-PC] arm.

Patients in each treatment arm received up to 5 cycles of the following: Brentuximab vedotin + AVEPC arm: brentuximab vedotin 1.8 mg/kg over 30 minutes (Day 1), doxorubicin 25 mg/m² (Days 1 and 2), vincristine 1.4 mg/m² (Day 8), etoposide 125 mg/m² (Days 1-3), prednisone 20 mg/m² BID (Days 1-7), cyclophosphamide 600 mg/m² (Days 1 and 2); or ABVE-PC arm: doxorubicin 25 mg/m² (Days 1 and 2), bleomycin 5 units/m² (Day 1) and 10 units/m² (Day 8), vincristine 1.4 mg/m² (Days 1 and 8), etoposide 125 mg/m² (Days 1-3), prednisone 20 mg/m² BID (Days 1-7), cyclophosphamide 600 mg/m² (Days 1 and 2).

The main efficacy outcome measure was event-free survival (EFS), defined as the time from randomization to the earliest of disease progression or relapse, second malignancy, or death due to any cause. Median EFS was not reached in either arm. There were 23 events (8%) in the brentuximab vedotin + AVEPC arm and 52 events (17%) in the ABVE-PC arm with a corresponding hazard ratio of 0.41 (95% CI: 0.25, 0.67; p=0.0002).

The most common Grade >=3 adverse reactions (>=5%) in pediatric patients treated with brentuximab vedotin in combination with AVEPC were neutropenia, anemia, thrombocytopenia, febrile neutropenia, stomatitis, and infection. The recommended brentuximab vedotin dose for pediatric patients 2 years of age and older is 1.8 mg/kg up to a maximum of 180 mg in combination with AVEPC every 3 weeks for a maximum of 5 doses.

ITI-3000 in Development for the Treatment of Merkel Cell Carcinoma

The FDA granted Fast Track designation to the ITI-3000 program for the treatment of patients with Merkel cell carcinoma (MCC). Researchers are currently enrolling in a Phase I study evaluating ITI-3000, a plasmid DNA vaccine targeting patients with MCC, a rare but aggressive form of skin cancer that is typically caused by the Merkel cell polyomavirus (MCPyV).

ITI-3000 leverages the investigational UNiversal Intracellular Targeted Expression (UNITE) platform, powered by LAMP (lysosome-associated membrane protein), which fuses sequences from the mutated form of the large T antigen of the MCPyV into the sequence of the LAMP-1 gene. This lysosomal targeting technology has been shown to result in enhanced antigen presentation and a balanced immune response, including ITI-3000 activated antigen-specific CD4+ T cells in vivo.

The platform leverages the ability to engineer chimeric proteins, directing antigen-presenting cells to present antigens to the immune system through a targeted pathway and driving a robust immune response. These vaccines are distinct in that they combine two components: nucleic acid constructs that encode a specific antigen and an endogenous LAMP-1 sequence.

The platform harnesses LAMP-1 as a means of presenting the vaccine target to the immune system, resulting in antibody production, inflammatory cytokine release, and establishing critical immunological memory, which is something that other vaccine approaches commonly lack. This approach could put this technology at the crossroads of immunotherapies in multiple indications, including cancer, human allergy, animal health, and infectious disease. Preclinical data is currently being developed to explore whether LAMP-1 nucleic acid constructs may amplify and activate the immune response in highly immunogenic tumor types and be used to create immune responses in tumor types that otherwise do not provoke an immune response.

Orphan Drug Designation of OTX-2002 for Hepatocellular Carcinoma

The FDA granted Orphan Drug Designation for OTX-2002, a first-in-class epigenomic controller engineered to downregulate c-Myc (MYC) for the treatment of hepatocellular carcinoma (HCC). The first patient had been dosed in the Phase I/II MYCHELANGELO I clinical trial investigating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of OTX-2002 as a monotherapy and in combination with standard-of-care therapies in patients with relapsed or refractory HCC and other solid tumor types known for association with the MYC oncogene.

OTX-2002 is a first-in-class Omega Epigenomic Controller in development for the treatment of HCC. It is an mRNA therapeutic delivered via lipid nanoparticles and is designed to downregulate MYC expression pre-transcriptionally through epigenetic modulation while potentially overcoming MYC autoregulation. MYC is a master transcription factor that regulates cell proliferation, differentiation, and apoptosis and plays a significant role in more than 50 percent of all human cancers. OTX-2002 is currently being evaluated in the Phase I/II MYCHELANGELO I trial in patients with relapsed or refractory HCC and other solid tumor types known for association with the MYC oncogene.