3C-14-1: A Phase 2 Clinical Trial of Nivolumab and Nivolumab Plus Ipilimumab in Recurrent and Metastatic Microsatellite High (MSI-H) Colon Cancer
This is a Phase 2 open-label, multi-center, 2-stage Simon design stage trial of nivolumab (BMS-936558) monotherapy (mStage) or in combination with ipilimumab (cStage) to estimate the response rate in Metastatic Microsatellite MSI-High colon cancer. Ipilimumab is a fully humanized IgG1 monoclonal antibody binding to the anti-cytotoxic T-cell lymphoma-4 antigen (CTLA-4). Ipilimumab is an approved therapy for metastatic melanoma.Nivolumab (BMS-936558; anti-PD-1 mAb) is a fully human monoclonal immunoglobulin (Ig) G4 antibody that binds to the programmed death-1 (PD-1), a negative regulatory molecule expressed by immune cells.Primary Objective of the study is to evaluate the objective response rate (ORR) of nivolumab monotherapy or nivolumab combined with ipilimumab in subjects with metastatic MSI-H colon cancer.The study will also contain a safety cohort of subjects with non-MSI-H colon cancer to assess the safety and tolerability of nivolumab in combination with ipilimumab in subjects with non-MSI-H colon cancerBoth Arms N and N+I will follow a two-stage design to test whether nivolumab monotherapy or nivolumab combined with ipilimumab yields an objective response rate (ORR) that is of clinical interest in MSI-H metastatic colorectal cancer mCRC. On treatment stages that meet an ORR threshold will proceed from Stage 1 to Stage 2 (same for both m and cStage). The primary endpoint of this study ORR which is based on tumor assessments at baseline and then at 6 weeks from first dose and continue every 6 weeks for the first 24 weeks and every 12 weeks thereafter until disease progressionThe study will enroll 96 patients out of which 15 will be enrolled at USC
Not recruiting | Colon / Rectal Cancer | Multisite
A Phase 1, Open-Label, Multi-Center, Dose Escalation and Expansion Study Evaluating the Safety, Tolerability and Clinical Activity of DECOY20 in Patients With Advanced Solid Tumors
Decoy20, is a novel, systemically administered multiple Toll-like receptor (TLR)
agonist-based cancer immunotherapy.
INDP-D101 is a Phase 1, open-label, multi-center, 3+3 dose escalation and expansion study
evaluating the safety, tolerability and clinical activity of Decoy20 in subjects with
advanced solid tumors. The study will include 3 parts:
In Part 1, Subjects will receive a single dose of Decoy20 at one of up to seven assigned dose
levels on Week 1 Day 1 (SAD). Subjects will be observed for 28 days for dose limiting
toxicity. Safety will be assessed by a safety review committee (SRC), comprised of
investigators and the study sponsor, and subsequently will recommend the dose of Decoy20 to
take forward.
Part 2 will begin when the single dose recommended from Part 1 is identified and it will
confirm the safety of weekly administration of Decoy20 in approximately 54 to 90 subjects.
More than one dose may be studied in Part 2 that is at or below the MTD determined in Part 1.
Eligible subjects must have one of the following locally advanced or metastatic tumor types:
hepatocellular carcinoma (HCC), colorectal cancer (CRC) with liver metastasis, urothelial
cancer, squamous cell carcinoma of the head and neck (SCCHN), adenocarcinoma of the pancreas,
non-small cell lung cancer (NSCLC). Part 2 is further divided into 2 parts a Safety Run-In
(Part 2a) and a Dose Expansion (Part 2b).
Part 2a will enroll 6 subjects in a staggered manner, and each subject will receive 4 weekly
doses of Decoy20 identified in Part 1. Safety data for each of these subjects will be
collected for 4 weeks after the subjects' 4th Decoy20 dose for acute and delayed toxicity.
This data will be reviewed by the SRC and the determination of the Decoy20 dose for Part 2b
made.
Part 2b will further evaluate and confirm the safety and preliminary efficacy of continuous
weekly Decoy20 administration for up to 1 year. The SRC will continue to meet and review data
on an ongoing or ad-hoc basis during Part 2b of the study to ensure that there are no undue
risks to study subjects and to confirm the RP2D and regimen.
A Phase 1 Study Evaluating the Safety and Efficacy of MAGE-A3/A6 T Cell Receptor Engineered T Cells (KITE-718) in HLA-DPB1*04:01 Positive Subjects With Advanced Cancers
Participants found to be human leukocyte antigen (HLA)-DPB1*04:01 positive and whose tumors
are MAGE-A3 and/or MAGE-A6 positive can participate if all eligibility criteria are met.
Other tests required to determine eligibility include a physical exam, electrocardiogram
(ECG) and echocardiogram (ECHO) of the heart, CT or MRI scans, and blood draws. Eligible
participants have white blood cells collected by leukapheresis. These cells are genetically
modified to make the experimental treatment KITE-718. The desired outcome is that the
genetically modified T cells will target tumor cells that express MAGE-A3 and/or MAGE-A6,
which are proteins that can be expressed by cancer cells. Participants receive chemotherapy
prior to the KITE-718 infusion. After the KITE-718 infusion, participants will be followed
for side effects and have scans performed to see any potential impact on their cancers. Study
procedures may be performed while hospitalized and/or in the outpatient setting. Subjects who
received an infusion of KITE-718 will complete the remainder of the 15 year follow-up
assessments in a separate long-term follow-up study, KT-US-982-5968
A Randomized Phase 2 Trial of Atezolizumab and Bevacizumab in Combination With SRF388 or Placebo in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma
This is a Phase 2 trial designed to evaluate the efficacy and safety of SRF388 in combination
with atezolizumab plus bevacizumab (Arm A) compared to placebo in combination with
atezolizumab plus bevacizumab (Arm B) in patients with first-line advanced or metastatic HCC.
After a Lead-In Phase of up to 30 patients who will receive open-label SRF388 + atezolizumab
+ bevacizumab, the blinded Randomized Phase will randomize approximately 104 patients with a
1:1 allocation to Arm A or Arm B and stratified by geographic region (Asia excluding Japan
vs. rest of world) and Barcelona Clinic Liver Cancer (BCLC) stage (B or C).
A Phase I, First-in-human, Open-label, Dose Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Oral TP 1454
Primary Objective:
• To establish the MTD and/or Recommended Phase 2 Dose (RP2D) of orally administered TP-1454
in patients with metastatic solid tumors and anal cancer.
Secondary Objectives:
- To establish the pharmacokinetic (PK) profile of orally administered TP-1454
- To observe patients for any evidence of antitumor activity of TP 1454 by objective
radiographic assessment
- To assess the safety and tolerability of TP-1454
A Phase 1/2 Study of LY3537982 in Patients With KRAS G12C-Mutant Advanced Solid Tumors
This is an open-label, multicenter Phase 1/2 study to evaluate safety, tolerability, and
preliminary efficacy of oral LY3537982 in patients with KRAS G12C-mutant solid tumors.
This study will be conducted in 3 parts: Phase 1a dose escalation, Phase 1b dose expansion
and dose optimization, and Phase 2.
KRAS G12C mutations will be identified through standard of care testing.
A Phase 1/2 Safety Study of Intratumorally Administered INT230-6 in Adult Subjects With Advanced Refractory Cancers
INT230-6 is comprised of a 3 agents in a fixed ratio - a cell permeation enhancer and two,
potent anti-cancer payloads (cisplatin and vinblastine sulfate). The penetration enhancer
facilitates dispersion of the two drugs throughout injected tumors and enables increased
diffusion into cancer cells. (Nonclinical safety studies showed no findings following drug
injection into healthy tissues.)
Historically physicians administer the two active drugs comprising INT230-6 by intravenous
(IV) infusion to achieve a systemic blood level at the limit of tolerability. The objective
is destroy both visible tumors and unseen circulating cancer cells (micro-metastases).
Unfortunately, dosing drugs IV delivers only a small amount with a low concentration at the
tumor site. This approach especially for late stage cancers is not highly effective and often
quite toxic to the patient.
Attempts at direct intratumoral injection with chemotherapeutic agents have not shown the
ability to treat the injected tumor, non-injected tumors or micro-metastases. This lack of
efficacy for local administration is due possibly to poor dispersion and a lack of cell
uptake of the agents.
Due to the use of the novel cell penetration enhancing agent INT230-6 treatment demonstrates
strong efficacy in animals having large tumors. The Sponsor's in vivo, non-clinical data
shows that INT230-6 thoroughly saturates and kills injected tumors. In addition, the drug
induces an adaptive (T-cell mediated) immune response that attacks not only the injected
tumor, but non-injected tumors and unseen micro-metastases. Cured animals become permanently
immunized against the type of cancer that INT230-6 eliminates.
Clinical trial IT-01 seeks to determine the safety and potential efficacy of dosing INT230-6
directly into several different types of cancers. In addition animal studies showed a strong
synergy of INT230-6 with immune modulation agents. Thus as part of study IT-01 the Sponsor
seeks to understand the safety and efficacy of INT230-6 when administered in combination with
immuno-therapeutic agents such as antibodies that target Programmed Cell Death (PD-1 or
anti-PD-1) and Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA-4 or anti-CTLA-4) receptors.
This study seeks to understand whether tumor regression can be achieved and patient outcomes
improved.
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