TG4010 immunotherapy improved survival of NSCLC patients in a Phase 2b trial
The TG4010 therapeutic vaccine (Transgene) was successful in treatment of advanced non-small cell lung cancer (NSCLC), according to a study published in Lancet Oncology.1 The randomized, double-blind Phase 2b TIME trial compared TG4010 to placebo, both in combination with chemotherapy, in >220 subjects. The experimental group showed improvements in progression-free survival, overall survival, response rate and duration of response. The benefit was most notable in patients with the low CD16, CD56, CD69 triple-positive activated lymphocytes biomarker.
NSCLC, the most common type of lung cancer, is associated with one of the worst prognoses among all cancer types. TG4010 expresses tumor-associated antigen MUC1 and the stimulating cytokine IL-2. In addition to NSCLC, MUC1 is expressed in breast, colorectal, kidney and prostate cancers.
1. Quoix E, Lena H, Losonczy G, Forget F, Chouaid C, Papai Z, Gervais R, Ottensmeier C, Szczesna A, Kazarnowicz A, Beck JT, Westeel V, Felip E, Debieuvre D, Madroszyk A, Adam J, Lacoste G, Tavernaro A, Bastien B, Halluard C, Palanché T, Limacher JM. TG4010 immunotherapy and first-line chemotherapy for advanced non-small-cell lung cancer (TIME): results from the phase 2b part of a randomised, double-blind, placebo-controlled, phase 2b/3 trial. Lancet Oncol 2015; doi: 10.1016/S1470-2045(15)00483-0
RSV vaccine has entered a maternal-immunization Phase 3 trial
A randomized, observer-blinded and placebo-controlled Phase 3 study in pregnant women has started for respiratory syncytial virus (RSV) vaccine candidate RSV F (Novavax). It will enroll and monitor >5,000 pregnant women for 2-4 years and assess efficacy of the vaccine in protecting infants from RSV infection through the first 3 months of their lives.
There is no available RSV vaccine. RSV F received the U.S. Food and Drug Administration (FDA)'s Fast Track designation in 2014. RSV is the most common cause of lower respiratory tract infections in children with >60 million cases and 160,000 deaths every year.
Pembrolizumab beneficial in NSCLC patients, enters trials for treatment of other cancers
The checkpoint inhibitor pembrolizumab (Keytruda, Merck) was successful in a randomized, open-label, Phase 2/3 study involving >1,000 patients with advanced PD-L1-positive NSCLC. The MAb extended overall survival compared to the chemotherapy drug docetaxel, according to the results published in Lancet.1
“This treatment provides real hope of long-lasting responses while avoiding the toxicities of typical chemotherapy in a broad population of lung cancer patients,” senior author Edward Garon of University of California, Los Angeles said in a statement.
Pembrolizumab will also be tested for efficacy against other types of cancer as a part of combination therapy: with blinatumomab (Blincyto) and AMG 820 MAbs (both Amgen) in treatment of B-cell lymphoma and advanced solid (NSCLC, pancreatic and colorectal) tumors, respectively.
1. Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 2015; doi: 10.1016/S0140-6736(15)01281-7
Clostridium difficile vaccine candidate safe and immunogenic
A high level of immunogenicity and very good safety and tolerability were reported from a Phase 2 trial of a Clostridium difficile vaccine candidate (Valneva). The study involved 500 subjects ≥50 years old from the U.S. and Germany randomized into four groups: placebo, low-dose vaccine without adjuvant, and high-dose vaccine with or without adjuvant. The last group generated superior immune responses.
C. difficile infection affects mostly older adults in a hospital or long-term-facility setting after antibiotic treatment and gut flora depletion. No vaccine is available against the infection, which is estimated to cost the U.S. almost $10 billion annually.
U.S. clinical trials have resumed for a grass allergy vaccine
The subcutaneous grass allergic rhinitis vaccine Pollinex Quattro Grass (Allergy Therapeutics) has started a double-blind, placebo-controlled, cumulative dose selection Phase 2 trial in the U.S. The vaccine has been approved in Europe for some years, but the FDA put its clinical testing on hold in 2007, when a volunteer experienced numbness and weakness during a trial.
Another Phase 2 study is underway for a birch pollen allergy vaccine candidate, PQBirch204 (Allergy Therapeutics). This placebo-controlled trial has recruited >360 subjects to assess efficacy and optimal dosing.
Additional dose of influenza vaccine offers better protection for cancer patients
A new vaccination strategy has been found to better protect immunocompromised cancer patients from influenza. Subjects with multiple myeloma and other plasma-cell disorders do not mount sufficient immune responses to a single vaccine dose, and are therefore susceptible to influenza.
Researchers at Yale and Icahn School of Medicine NY evaluated an immunization schedule consisting of two Fluzone High Dose injections one month apart, and found a decrease in influenza infection among patients with plasma-cell disorders to 6%, compared to an expected rate of 20%. Additionally, 66% of the subjects showed improved protection against all strains covered by the vaccine. A larger randomized study is underway.
T-vec immunotherapy approved for inoperable melanoma in Europe
The European Commission has approved talimogene laherparepvec (T-Vec, Amgen) immunotherapy for inoperable melanoma, except in patients whose tumors have spread to the brain, bone, lungs or gut. T-Vec (Imlygic) is an engineered herpes virus injected into the tumor, where it replicates to kill cancer cells and elicit an immune response. It is the first oncolytic therapy approved in the E.U.
This approval and a recent approval by the FDA were supported by data from the Phase 3 OPTiM trial, in which T-Vec shrank tumors at a significant rate. It is being tested in combination with PD-1 inhibitors in advanced melanoma, head-and-neck, colon and breast cancers.
New Dengue vaccine approved in the first three countries
Mexico, Philippines and Brazil have become the first countries to approve the dengue vaccine Dengvaxia (Sanofi). Transmitted via the mosquito Aedes aegypti, dengue fever affects almost 400 million people each year, and accounts for >12,000 deaths. It has been on the rise recently, with the number of cases tripling from 2014 to 2015 in Brazil.
In two Phase 3 trials, Dengvaxia protected 2/3 of subjects aged ≥9 years from all 4 serotypes, and >90% were protected against severe dengue. Following another successful study with Indian adults, the Indian government has initiated talks with the company with the aim to accelerate authorization of the vaccine and possibly exempt Dengvaxia from the requirement of large-scale local trials.
Gardasil 9 approved for males 9-26 years old
The FDA has expanded the approval of HPV vaccine Gardasil 9 (Merck) to include males aged 16-26. Together with previous indications, Gardasil 9 is now approved for both males and females 9-26 years of age. The recombinant vaccine prevents anal cancers and genital warts caused by 9 HPV strains. In females, it is estimated to prevent 90% of cervical cancer cases.
Gardasil 9 includes more virus strains than any other vaccine. It has been recommended by the U.S. CDC's Advisory Committee on Immunization Practices for routine use. HPV causes ~90% of anal cancers and genital warts in both sexes, and virtually all cervical cancers in women.
FDA has granted Priority Review to cholera vaccine Vaxchora
The FDA has accepted a license application for Vaxchora cholera vaccine (PaxVax) under a priority review. The candidate met primary endpoints of a 3,000-subject Phase 3 trial. If approved, it will become the first cholera vaccine available in the U.S., and the first single-dose cholera vaccine. Two other two-dose vaccines, Dukoral (Valneva) and Shanchol (Shantha), have not yet been approved for U.S. travelers.
Vaxchora is a live attenuated vaccine containing CVD 103-HgR strain of Vibrio cholerae. The infection affects up to 5 million people and leads to >100,000 deaths annually.
Chikungunya vaccine progresses to Phase 2 clinical trial
A Chikungunya fever vaccine candidate developed by the U.S. National Institute of Allergy and Infectious Diseases has entered a Phase 2 trial in the Caribbean. The virus-like particle vaccine had been shown to be highly immunogenic in a group of 25 people. The current study will enroll ~400 healthy volunteers 18–60 years old, divided into two groups receiving two doses of vaccine or placebo 28 days apart.
The mosquito-borne Chikungunya infection has become a considerable burden in the Americas since its emergence in 2013. Although the fever usually wanes in a week, joint pains can persist for months or years, and the disease can lead to death in older people.