The Lung Cancer Master Protocol is undergoing a major expansion to include patients with all non-small cell lung cancers.
The trial previously tested treatments for people with advanced stage squamous cell lung cancer. The trial is now open to all types of advanced stage non-small cell lung cancers. NSCLC makes up about 85 percent of all lung cancer diagnoses in the U.S.
This month, Lung-MAP will undergo other key changes. These include:
A new screening protocol to include the addition of liquid biopsies, as well as a streamlined informed consent form that combines screening and prescreening—a step that will make it easier to enroll patients.
Two new drug sub-studies, one testing a PARP inhibitor and another testing a PD-L1 and VEGF inhibitor in combination scheduled to open in early 2019. Two more sub-studies are in development and are scheduled to open in late summer 2019.
A new mandate that requires hospitals, clinics, and other sites that open the trial to use the NCI’s Central Institutional Review Board to oversee trial changes, another move to speed the process of opening the trial at sites and registering patients.
Lung-MAP is the first large-scale precision medicine trial in lung cancer backed by the NCI and the first major NCI cancer trial to test multiple treatments, simultaneously, under one “umbrella” design.
Lung-MAP is also a groundbreaking public-private partnership, one that includes the NCI and its National Clinical Trials Network including SWOG Cancer Research Network, Friends of Cancer Research, the Foundation for the National Institutes of Health, Foundation Medicine, and pharmaceutical companies which provided their drugs for the study, and several lung cancer advocacy organizations.
Since it launched in June 2014, Lung-MAP has registered more than 1,700 patients across the country. Trial leaders have worked with 10 pharmaceutical partners, in coordination with the FNIH, to launch nine studies, six of which are completed.
The new trial is also addressing questions about the efficacy of immunotherapies and immunotherapy combinations and the validity of new biomarkers. The trial has also produced insights into the conduct of large-scale precision medicine trials, including tissue sampling and banking, genetic screening, and patient communication, its sponsors say.
Alimta + Keytruda and platinum chemo for NSCLC gets FDA label expansion
Eli Lilly and Co. said FDA has granted approval for a new indication for Alimta (pemetrexed for injection) in combination with Keytruda (pembrolizumab), developed and marketed by Merck, and platinum chemotherapy for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer, with no EGFR or ALK genomic tumor aberrations.
This indication is approved based on data from Merck’s phase III KEYNOTE-189 trial, which enrolled patients regardless of PD-L1 expression and had dual primary endpoints of overall survival and progression-free survival.
Alimta in combination with pembrolizumab and carboplatin was first approved in June 2018 under the FDA’s accelerated approval process for the first-line treatment of patients with metastatic nonsquamous NSCLC, based on tumor response rates and PFS data from the phase II study KEYNOTE-021 (Cohort G1).
In accordance with the accelerated approval process, continued approval was contingent upon verification and description of clinical benefit, which has now been demonstrated in the KEYNOTE-189 trial and has resulted in the FDA converting the accelerated approval to full approval.
“KEYNOTE-189 demonstrated an exceptional effect of the Alimta-pembrolizumab-platinum chemotherapy combination in the first-line setting, offering significantly improved survival in patients with metastatic nonsquamous non-small cell lung cancer with no EGFR or ALK genomic tumor aberrations,” Anne White, president, Lilly Oncology, said in a statement. “This new indication reinforces Lilly’s continued commitment to providing practice-changing treatment options that can make a meaningful difference for people living with lung cancer.”
Alimta is contraindicated in patients who have a history of severe hypersensitivity reaction to pemetrexed. See additional Important Safety Information below.
On Aug. 20, 2018, Merck’s pembrolizumab was approved by FDA for this indication, based on data from the KEYNOTE-189 study, which demonstrated that treatment with Alimta in combination with pembrolizumab plus platinum-based chemotherapy resulted in significantly longer OS and PFS than Alimta plus platinum chemotherapy with placebo.
Trovagene and PoC Capital agree to fund clinical development of onvansertib in metastatic colorectal cancer
Trovagene Inc. announced an agreement with PoC Capital to fund clinical development of onvansertib, Trovagene’s first-in-class, 3rd generation oral and highly selective Polo-like Kinase 1 inhibitor in a phase Ib/II clinical trial in patients with metastatic colorectal cancer.
Trovagene submitted an Investigational New Drug application and protocol to the FDA on Dec.19, 2018, and received a “study may proceed” notification from the FDA, 28-days later, on Jan. 16, 2019.
The trial will be conducted at two prestigious cancer centers in the U.S.; USC Norris Comprehensive Cancer Center and Mayo Clinic. Onvansertib, its lead drug candidate, is a first-in-class, 3rd generation, highly-selective oral Polo-like Kinase 1 Inhibitor. The company currently has two ongoing open-label clinical trials: a phase Ib/II trial in acute myeloid leukemia and a phase II trial in metastatic castration-resistant prostate cancer.
In this open-label, phase Ib/II trial, onvansertib in combination with standard-of-care FOLFIRI and Avastin is being evaluated for safety and efficacy. The trial, “A phase Ib/II Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second‑Line Treatment of Metastatic Colorectal Cancer in Patients with a Kras Mutation”, will enroll up to 44 patients with a Kras mutation and histologically confirmed metastatic and unresectable disease.
In addition, patients must have failed treatment or be intolerant of FOLFOX (fluoropyrimidine and oxaliplatin) with or without Avastin (bevacizumab). The trial is being conducted at two prestigious cancer centers: USC Norris Comprehensive Cancer Center and The Mayo Clinic Arizona.
Onvansertib is a first-in-class, 3rd generation, oral and highly-selective adenosine triphosphate competitive inhibitor of the serine/threonine polo-like-kinase 1 enzyme, which is over-expressed in multiple cancers, including leukemias, lymphomas and solid tumors.
Separate studies with other PLK inhibitors have shown that inhibition of polo-like-kinases can lead to tumor cell death, including a phase II study in AML where response rates of up to 31% were observed when combined with a standard therapy for AML (low-dose cytarabine-LDAC) versus treatment with LDAC alone with a 13.3% response rate.
A phase I open-label, dose escalation safety study of onvansertib has been completed in patients with advanced metastatic solid tumor cancers and published in Investigational New Drugs. The maximum tolerated dose or recommended phase II dose in this trial was 24 mg/m2.
Onvansertib targets the PLK1 isoform only, is orally administered, has a 24-hour drug half-life with only mild to moderate side effects reported. Trovagene believes that targeting only PLK1 and having a favorable safety and tolerability profile, along with an improved dose/scheduling regimen will significantly improve on the outcome observed in previous studies with a former panPLK inhibitor in AML.
Onvansertib has demonstrated synergy in preclinical studies with numerous chemotherapies and targeted therapeutics used to treat leukemias, lymphomas and solid tumor cancers, including FLT3 and HDAC inhibitors, taxanes, and cytotoxins.
Trovagene believes the combination of its targeted PLK1 inhibitor, onvansertib, with other compounds has the potential to improve clinical efficacy in AML, metastatic castration-resistant prostate cancer, non-Hodgkin lymphoma, triple negative breast cancer, as well as other types of cancer.
Trovagene has an ongoing phase Ib/II clinical trial of onvansertib in combination with low-dose cytarabine or decitabine in patients with relapsed or refractory AML that was accepted by the National Library of Medicine and is now publicly viewable on www.clinicaltrials.gov.
The NCT number assigned by clinicaltrials.gov for this study is NCT03303339. Onvansertib has been granted Orphan Drug Designation by the FDA in the U.S. and by the EC in the European Union for the treatment of patients with AML.
Trovagene has an ongoing phase II clinical trial of onvansertib in combination with Zytiga (abiraterone acetate)/prednisone in patients with metastatic castrationrresistant prostate cancer who are showing signs of early progressive disease (rise in PSA but minimally symptomatic or asymptomatic) while currently receiving Zytiga.
The trial was accepted by the National Library of Medicine and is now publicly viewable on www.clinicaltrials.gov. The NCT number assigned by clinicaltrials.gov for this study is (NCT03414034).