Introduction to Phase Trials

RESULTS Most of the 876 clinical trials analyzed were funded by external pharmaceutical companies and corresponded to late-phase trials.

These results formed the basis for ongoing futibatinib phase II/III trials and demonstrate the potential of genomically selected early-phase trials to help identify molecular subsets likely to benefit from targeted therapy.

The EC50 image could add value to early-phase drug development by identifying regional variation in affinity that might impact therapy or safety and by guiding dose selection for later-phase trials.

This includes early-phase trials designed not only to inform about drug dosing, safety and tolerability, but also to provide sufficient confidence on target engagement or potential efficacy to support progression to the much more costly later-phase studies.

ADs can be applied from early-phase trials to confirmatory trials.

The goal of a universal influenza vaccine targeting conserved regions of the virus and avoiding the need for annual vaccination is edging closer with early-phase trials under way.

While some ablative treatments have received approval from the FDA authorities for application in the prostate, at present many other ablative techniques are being studied in early-phase trials.

While one biologic has recently received FDA-approval, the majority of products remain investigational and in early-phase trials.

Here, we review the pre-clinical and clinical trials that led to the approval of fedratinib, and the ongoing late-phase trials.

Despite differences in clinical and behavioral characteristics, these disorders have shared pathologies and face common challenges in designing early-phase trials that are predictive of late-stage success.

These results support including elderly patients with cancer in early-phase trials.

Late-phase trials were published at higher rate (74.

The present paper aims to review the current evidence and the methodology of early-phase trials in oral cancer chemoprevention.

Several groups have carried out early-phase trials of various CAR-T cell constructs in adults with r/r B-ALL.

It is intended to answer the questions about efficacy and safety, which lack in phase trials, especially at community level.

Knowledge gaps in all five therapeutic classes can be attributed to the lack of: (1) a unifying conceptual framework for evaluating therapeutic mechanisms of action; (2) large-scale randomized controlled trials; and (3) pharmacodynamic biomarkers that measure subclinical therapeutic effects in early-phase trials.

The aims of Phase 1 trials in oncology have broadened considerably from simply demonstrating that the agent/regimen of interest is well tolerated in a relatively heterogeneous patient population to addressing multiple objectives under the heading of early-phase trials and, if possible, obtaining reliable evidence regarding clinical activity to lead to drug approvals via the Accelerated Approval approach or Breakthrough Therapy designation in cases where the tumours are rare, prognosis is poor or where there might be an unmet therapeutic need.

Initial models were developed based on data sets from early‐phase trials and qualified using external data from the phase III MONALEESA‐2 trial.

25%); conversely, academia sponsored more phase-2 and late-phase trials (39% and 31% vs.

In these later-phase trials, evidence that the therapeutic candidate is altering disease-related biomarkers can provide important evidence that the clinical benefit of the compound (if observed) is grounded in meaningful biological changes.

Single-agent anti-PD-1 immune checkpoint inhibitors (ICIs) demonstrated promising efficacy in early-phase trials, a finding that was not confirmed in phase III studies.

Finally, the results of phase trials are waited to learn whether or not the newer agents such as molnupiravir, PF-07321332, PF-07304814, plitidepsin and AT-527 are effective in the treatment of COVID-19.

Although recent outcomes of early-phase trials have showed that several drugs presented an ideal curative effect, monotherapy cannot be entirely satisfactory in the treatment of cachexia-associated symptoms due to its complex and multifactorial pathogenesis.

Objectives Individual participant data (IPD) from placebo arms of interventional trials were sought to determine whether short-term changes in forced vital capacity (FVC), gas transfer for carbon monoxide (DLCO) and six-minute walk distance (6MWD) could act as surrogate endpoints to accelerate early-phase trials in IPF.

In this article, we discuss four levels of evidence—target antigen immunohistochemistry, in vitro and in vivo preclinical experiments, animal biodistribution and dosimetry studies, and first-in-human microdose biodistribution studies—that might be used to justify oncology therapeutic radiopharmaceuticals in a drug-development sequence involving early-phase trials.

There is currently insufficient emphasis on the role of randomization in expansion cohorts and phase 2 components of early-phase trials.

Background/Aim: Pseudomonas exotoxin (PE) is one of the most widely used toxins in the construction of therapeutic fusion proteins in pre-clinical studies followed by phase trials.

However, many of the new drugs either do not progress from phase I-II clinical trials or even fail in late-phase trials.

Early-phase trials on cancer drugs are frequently used in reimbursement submissions to the pan-Canadian Oncology Drug Review (pCODR) committee of the Canadian Agency for Drugs and Technologies in Health (CADTH), according to findings of a study published in PharmacoEconomics.

Therefore, in this study, a series of multi-compartment–baffled flow trials were performed to assess the effects of phase separation on sludge bioleaching by comparing a two-phase trial with two single-phase trials.

Three early-phase trials—KEYNOTE-051, iMATRIX, and ADVL1412—were the first to describe irAEs in pediatric patients and ICIs were well tolerated.

We present an integrated efficacy and safety analysis of patients with metastatic or locally advanced solid tumours harbouring oncogenic NTRK1, NTRK2, and NTRK3 gene fusions treated in three ongoing, early-phase trials.

We hope that MoDEsT will enable incorporation of Bayesian decision procedures for dose escalation at the earliest stage of clinical trial design, thus increasing their use in early-phase trials.

The goal of these designs is to select the optimal drug dose for further phase trials more accurately than dose finding designs that only consider toxicity, such as the 3 + 3, TEQR (toxicity equivalence range), mTPI (modified toxicity probability interval), and EWOC (escalation with overdose control) designs.

We conclude that these results should allow early-phase trials of therapy in RHO-adRP to move forward by inclusion of patients with an asymmetric extent of photoreceptor structure and by monitoring therapeutic effects over two years in the superior retina, a reasonable target for subretinal injection.

Cell-specific yields are at the upper end of those previously reported in the literature, and volumetric yields are in the range 1 × 1013 – 5 × 1013 purified virus particles per litre of culture, such that a 2–4 L process is comfortably adequate to produce vaccine for early-phase trials.

EVIDENCE SYNTHESIS Prospective early-phase trials investigating neoadjuvant immunotherapy prior to cystectomy in urothelial carcinoma suggest a high rate of pathological complete response, from 29% with atezolizumab to 39.

Methods: We propose an adaptive dose-finding method that integrates accumulating feasibility and safety data to select doses for participant cohorts in early-phase trials examining adoptive cell immunotherapy.

Conclusion: In contrast to traditional early-phase trials that use symptom severity to track treatment efficacy, this study tracks engagement of the study drug on expression of behavioral sensitization, a functional mechanism likely to cut across disorders.

BackgroundAlthough translational research for drug development can provide patients with valuable therapeutic resources it is not without risk, especially in the early-phase trials that present the highest degree of uncertainty.

Although results in NHL were disappointing, parallel testing in early-phase trials of CD22+ ALL demonstrated feasibility and efficacy.

A literature search was conducted using the keywords “anti-CD6”, “psoriasis”, “phase trials”, “case series”, and “case reports”.

An extensive review was performed to assess if the OBDs defined in early-phase trials were useful for subsequent drug development and approvals.

The variation of symptom burden by performance status and age suggest that these factors need to be considered in the design of early-phase trials, particularly if patient-reported symptoms are used as primary/secondary/exploratory endpoints.