Out of the starting gate

A roundup of clinical trial startups and initial breakthroughs

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PLYMOUTH MEETING, Pa.—Inovio Pharmaceuticals Inc. announced Aug. 16 that it had dosed its first patient in a Phase 1/2a study designed to evaluate the safety, immunogenicity and clinical efficacy of INO-5401, the company’s novel cancer immunotherapy that encodes multiple cancer antigens, plus INO-9012, a T cell activator, in combination with atezolizumab, a PD-L1 inhibitor, for the treatment of advanced or metastatic bladder cancer. The trial, which is being managed by Inovio, is expected to enroll approximately 85 patients at sites located in the United States and Spain.
“We are very encouraged to dose our first patient, with the aspiration that we can demonstrate the immense potential of our INO-5401 immunotherapy to treat advanced bladder patients as well as those with other cancers,” said Dr. J. Joseph Kim, Inovio's president and CEO. “This also marks the second time in less than a month that Inovio has dosed a cancer patient, combining INO-5401, our T cell-generating immunotherapy, with a checkpoint inhibitor. Bladder cancer is considered an immunogenic tumor, and our approach is to combine INO-5401/INO-9012 with atezolizumab, as we believe this may provide a synergistic therapeutic effect by generating functional and activated T cells while simultaneously inhibiting PD-L1. We remain on track and look forward to producing interim clinical results in 2019.”
This open-label, multi-center Phase 1/2a study plans to enroll 85 patients divided into two cohorts. Cohort A includes patients with confirmed disease progression during or following prior checkpoint inhibitor therapy, while cohort B patients are treatment-naïve and unfit for cisplatin-based therapy.
INO-5401 includes Inovio’s SynCon antigens for hTERT, WT1 and PSMA, and the company believes this has the potential to be a powerful cancer immunotherapy in combination with checkpoint inhibitors. The National Cancer Institute previously highlighted hTERT, WT1 and PSMA among a list of important cancer antigens, designating them as high priorities for cancer immunotherapy development.
In other recent news from Inovio, the company announced that the first participant had been dosed with PENNVAX-GP in a randomized clinical trial that will evaluate its ability to drive remission of HIV infection. This vaccine widely targets all major HIV strains and has the potential to enhance the capacity of the immune system to eliminate or provide lifelong control of HIV. This trial is part of a previously reported multi-year, $6.95-million grant from the National Institute of Allergy and Infectious Diseases to develop a single or combination therapy using Inovio’s PENNVAX-GP with the goal of attaining long-term HIV remission.

Immatics initiates second phase for its ACTengine platform
HOUSTON—In other news of clinical trial startups, Immatics recently announced that it had initiated enrollment of patients into a Phase 1 trial of IMA202, its second T cell receptor (TCR)-transduced adoptive cell therapy program. IMA202 is an investigational immunotherapy which uses Immatics’ proprietary ACTengine approach and is based on genetic engineering of the patient’s own T cells to express an exogenous TCR. The goal is to redirect and activate the T cells to treat solid tumors. The single-center clinical study is now open for enrollment at The University of Texas MD Anderson Cancer Center.
The study (IMA202-101) will include approximately 12 patients with relapsed and/or refractory solid tumors, including but not limited to advanced non-small cell lung cancer and hepatocellular carcinoma, for which no standard-of-care therapy is available.
Immatics’ ACTengine approach engineers the patients’ own T lymphocytes to express a novel, exogenous TCR which is targeted to a site on the tumor identified by Immatics’ proprietary XPRESIDENT target discovery platform.
The primary objective of the study is to evaluate the safety and tolerability of the ACTengine approach—and specifically IMA202—in target-positive solid cancer patients. The secondary objectives include the evaluation of feasibility, the persistence of T cells in vivo and the assessment of antitumor activity and biomarkers.
“Regulatory approval to start our second clinical study in our ACTengine-based cell therapy program is a significant step for Immatics. This study exemplifies Immatics’ XPRESIDENT target discovery capability and TCR discovery pipeline, which are industry-leading cancer immunotherapy platforms,” said Dr. Stephen L. Eck, chief medical officer of Immatics US.

ADC doses first patient in pivotal trial of ADCT-402
LAUSANNE, Switzerland—Early August saw ADC Therapeutics report that the first patient had been dosed in its Phase 2 clinical trial intended to support the submission of Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA). The clinical trial is evaluating the efficacy and safety of ADCT-402 (loncastuximab tesirine) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
At the 2017 American Society of Hematology Annual Meeting, the company presented interim Phase 1 data on ADCT-402 in 138 evaluable, heavily pretreated lymphoma patients who had failed, or were intolerant to, any established therapy known to provide clinical benefit, with a median of three prior therapies. At the time, for the 49 response-evaluable patients in part one of the study (dose escalation) with DLBCL who received ADCT-402 at doses greater than or equal to 120 μg/kg, the overall response rate (ORR) was 55 percent, with 18 patients achieving a complete response (37 percent) and nine patients achieving a partial response (18 percent).
The primary endpoint of the Phase 2, multicenter, open-label, single-arm trial is the ORR in patients treated with ADCT-402, as confirmed by central review. Secondary endpoints include assessments of duration of response, complete response rate, relapse-free survival, progression-free survival and overall survival, as well as safety, pharmacokinetics and health-related quality of life. The trial will enroll approximately 140 patients with relapsed or refractory DLBCL at multiple centers in the United States and Europe.
“Our Phase 1 clinical trial of ADCT-402 in non-Hodgkin lymphoma showed significant activity in patients with DLBCL and an acceptable safety profile,” said Dr. Jay Feingold, chief medical officer and senior vice president of clinical development at ADC Therapeutics. “Unfortunately, there is no effective treatment for patients with multiple relapsed and refractory DLBCL, so we are excited about the potential to improve outcomes in these patients with ADCT-402 in a single-arm trial. We anticipate reporting results from the Phase 2 trial in the third quarter of 2019 and are hopeful that the data will support our submission of a BLA to the FDA.”

Cerecor initiates trial for neurogenic orthostatic hypotension in Parkinson’s disease
BALTIMORE—On Aug. 1, Cerecor Inc. noted that it had enrolled the first patient in a Phase 1 study of its proprietary drug candidate CERC-301 in patients with neurogenic orthostatic hypotension (nOH) associated with Parkinson’s disease. The study will evaluate the single-dose safety, tolerability and pharmacokinetics of CERC-301 in this patient population, as well as explore the effects on blood pressure and symptoms of nOH during an orthostatic challenge at escalating dose levels.
"With the first patient enrolled in our Phase 1 trial, we are now actively studying CERC-301 in nOH,” said Peter Greenleaf, CEO of Cerecor. “We are excited about the progress that our team has made in advancing the clinical development of CERC-301, which demonstrates the potential of our pipeline. We are transforming Cerecor into a fully integrated, innovation-driven specialty pharmaceutical company. Our intent is to leverage the profits of our commercial portfolio as fuel for innovation to support our clinical development programs.”
CERC-301 is an oral, NR2B-specific N-methyl-D-aspartate receptor antagonist that Cerecor is developing for treatment of nOH. In previous clinical studies, CERE-301 has demonstrated a pressor effect on blood pressure in healthy volunteers, Parkinson’s disease patients and patients with major depressive disorder.

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