Clinical Catch-Up: Amgen's Mixed Lumakras Data for Lung Cancer and More


Every week, dozens of biopharma companies and research institutions announce clinical trial updates. Here’s a look at just some of the more interesting ones.

Amgen announced two studies of Lumakras (sotorasib) for lung cancer with mixed results. The Phase Ib CodeBreak 100/101 dose exploration study of Lumakras plus Merck’s Keytruda (pembrolizumab) or Genentech’s Tecentriq (atezolizumab) demonstrated an objective response rate of 29% in the mostly pre-treated non-small cell lung cancer population. It had a higher incidence of grade 3 or 4 treatment-related adverse events (TRAEs), specifically high liver toxicity. The second study was the CodeBreak 101 trial of patients with KRAS G12C-mutated tumors who received Lumakras plus escalating doses of Revolution Medicine’s SHP2 inhibitor, RMC-4630. 

The patients had a median of three previous lines of therapy, with 41% receiving KRASG12C inhibitors. Of the 11 patients, 27% had a confirmed partial response, while 64% reported disease control. In the KRASG12C inhibitor-native patients, 50% had ORR and 6 had disease control. But there were TRAEs in 63% of participants, mostly edema and diarrhea.

Innovent Biologics dosed the first patient in the Phase I study of IBI324 for diabetic macular edema (DME). The drug is a potential first-in-class ophthalmic recombinant human anti-VEGF-A and anti-Ang-2 bispecific antibody. The Phase I dose escalations trial will evaluate the safety and tolerability of intravitreal injection of the drug in patients with DME. DME is a chronic, progressive complication of diabetes that causes impaired vision and even blindness from swelling of the central part of the retina.

HUTCHMED Limited announced its pivotal Phase III FRESCO-2 trial of fruquintinib hit the primary endpoint of overall survival (OS) in advanced, refractory metastatic colorectal cancer. It was run in the U.S., Europe, Japan and Australia. It evaluated the drug plus best supportive care compared to placebo plus best supportive care in metastatic CRC patients who had progressed on standard chemotherapy and relevant biologic agents and who had progressed on, or were intolerant to, TAS-102 and/or regorafenib. In addition to improved OS, it demonstrated a statistically significant improvement in progression-free survival (PFS). Fruquintinib is a highly selective and potential oral inhibitor of VEGFR-1, -2 and -3.

Veru presented Phase III COVID-19 trial data of Sabizabulin for hospitalized COVID-19 patients at high risk for Acute Respiratory Distress Syndrome (ARDS). Sabizabulin is an oral, novel microtubule disruptor with dual antiviral and anti-inflammatory properties. In the study in 204 hospitalized moderate-severe COVID-19 patients requiring oxygen who were at high risk for ARDS and death, a planned interim analysis was halted by the Independent Data Monitoring Committee for a clear demonstration of efficacy. The primary endpoint was all cause mortality by Day 60, a clinically meaningful and statistically significant 55.2% relative reduction in deaths was observed in the intent-to-treat population.

Saol Therapeutics enrolled the first patient in its Phase II COMPASS Osteoarthritis Pain Trial. It is evaluating SL-1002, a novel, proprietary, nerve-blocking agent. The study is a single ascending-dose escalation study and is being evaluated for the treatment of knee pain associated with osteoarthritis in adults. The first patient was enrolled in the International Spine, Pain and Performance Center in Washington, D.C. Efficacy and safety are the two primary endpoints in the trial.

LianBio completed enrollment in the Phase III EXPLORER-CN trial of mavacamten in Chinese patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). The primary endpoint is a change in Valsalva left ventricular outflow tract (LVOT) gradient from baseline to week 30. Eligible patients will continue in a long-term extension treatment period. LianBio licensed rights for the drug in August 2020 from MyoKardia, now a wholly owned subsidiary of Bristol Myers Squibb. They licensed the rights to develop and commercialize the drug in Mainland China, Hong Kong, Macau, Taiwan, Thailand and Singapore. It was approved in the U.S. under the brand name Camzyos for symptomatic New York Heart Association class II-III oHCM to improve functional capacity and symptoms. It is a cardiac myosin inhibitor.

Rani Therapeutics announced positive topline data from a single-ascending dose portion of its Phase I trial of RT-102 for osteoporosis. The drug is a proprietary formulation of human parathyroid hormone (PTH) analog PTH (1-34). The trial portion hit all endpoints, was well-tolerated and demonstrated high oral bioavailability. In addition, it demonstrated bioavailability greater than Eli Lilly’s subcutaneous Forteo (teriparatide).

Graphite Bio dosed the first patient with GPH101 for sickle cell disease (SCD) in a Phase I/II CEDAR trial. GPH101 or nulabeglogene autogedtemcel (nula-cel) is a gene editing therapy designed to directly correct the genetic mutation that causes SCD. It uses a differentiated gene correction approach to efficiently and precisely correct the mutation in the beta-globin gene to decrease sickle hemoglobin production and restore adult hemoglobin expression. The trial will evaluate about 15 patients with severe SCD.

Todos Medical announced that 3CL Pharma, its subsidiary, had finalized plans for a proposed safety and efficacy clinical trial for its 3CL protease inhibitor immune support dietary supplement Tollovid in patients with Long Covid. The 45-patient Part A will have three arms. It will evaluate the therapy’s effects on the structure and function of the immune system as measured by the presence of neutralizing antibodies, total anti-SARS-CoV-2 antibodies and VEGF cytokine levels. Tollovid and Tollovid Daily are oral dietary supplements made from natural ingredients with potent 3CL protease inhibition properties based on in vitro functional assays. They bind to the active site of the 3CL protease.

Aptinyx announced results from a Phase IIb trial of NYX-2925 in fibromyalgia. The drug failed to achieve statistically significant separation from placebo - in other words, it failed the trial - in its primary endpoint. The primary endpoint was a change from baseline in average daily pain on the numeric rating scale (NRS) during week 12. The company’s tech platform is used to discover novel compounds that modulate, instead of block or over-activate, NMDA receptors and enhance synaptic plasticity. The study evaluated approximately 300 patients with fibromyalgia who received a 50-mg, 100-mg dose or placebo once a day for the treatment period.

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