Decoy20 for Solid Tumors
Recruiting in Palo Alto (17 mi)
+9 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Indaptus Therapeutics, Inc
Must not be taking: Corticosteroids, Chemotherapy, Immunotherapy, others
Disqualifiers: Pregnancy, Active infection, CNS metastases, others
No Placebo Group
Trial Summary
What is the purpose of this trial?INDP-D101 is a Phase 1/2, open-label, multi-center, dose escalation and expansion study evaluating the safety, tolerability and clinical activity of Decoy20 as monotherapy and in combination with tislelizumab in patients with locally advanced or metastatic solid tumors.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received chemotherapy, targeted therapy, or immunotherapy within 28 days before starting the trial, and you should not be on systemic corticosteroids above a certain dose.
What data supports the effectiveness of the drug Decoy20 for treating solid tumors?
Research on similar treatments, like doxorubicin-loaded platelet decoys, shows potential in enhancing cancer therapy by combining chemotherapy with immune system activation, which might suggest a similar approach could be effective for Decoy20 in solid tumors.
12345Eligibility Criteria
Adults with advanced metastatic solid tumors who have had 1-3 prior treatments and progressed or were intolerant. They must have measurable disease, be in good physical condition (ECOG 0 or 1), not pregnant, using effective contraception, and have a life expectancy of at least 3 months. Participants need proper heart function (LVEF ≥45%) and adequate organ function.Inclusion Criteria
I am 18 years old or older.
My organs are working well, according to recent tests.
Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as defined by tumor type
+9 more
Exclusion Criteria
I have not had major uncontrolled bleeding or blood clot issues recently.
I don't have any health or mental conditions that could make this study riskier for me.
I am currently fighting an infection that needs treatment.
+19 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation (Part 1)
Subjects receive a single dose of Decoy20 at one of up to three assigned dose levels and are observed for 28 days for dose limiting toxicity.
4 weeks
1 visit (in-person) for dosing, followed by observation
Safety Run-In (Part 2a)
Subjects receive 4 weekly doses of Decoy20 identified in Part 1, with safety data collected for 4 weeks after the 4th dose.
8 weeks
4 visits (in-person) for dosing, followed by observation
Dose Expansion (Part 2b)
Continuous weekly administration of Decoy20 for up to 1 year to evaluate safety and preliminary efficacy.
up to 52 weeks
Combination Therapy (Part 2c)
Evaluation of Decoy20 in combination with tislelizumab, with ongoing safety and tolerability assessments.
up to 52 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment completion.
4 weeks
Participant Groups
The DECOY20 Study is testing the safety and effectiveness of a new treatment called Decoy20 for patients with advanced solid tumors. This Phase 1 trial involves gradually increasing doses to find the right balance between safety and potential benefits.
3Treatment groups
Experimental Treatment
Group I: Parts 2a and 2bExperimental Treatment1 Intervention
Decoy20 administered weekly at a dose of 3 x 10\^7 KB or 7 x 10\^7 KB
Group II: Part 2cExperimental Treatment2 Interventions
Decoy20 administered weekly at either 3 x 10\^7 KB or 7 x 10\^7 KB. Both will be administered with tislelizumab at 200mg Q3W.
Group III: Part 1Experimental Treatment1 Intervention
A single dose of Decoy20 at a dose of 3 x 10\^7 KB or 7 x 10\^7 KB
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cleveland Clinic Taussig Cancer CenterCleveland, OH
Fox Chase Cancer CenterPhiladelphia, PA
Washington University, Siteman Cancer CenterSt. Louis, MO
Prisma Health Cancer Institute-ITORGreenville, SC
More Trial Locations
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Who Is Running the Clinical Trial?
Indaptus Therapeutics, IncLead Sponsor
Translational Drug DevelopmentCollaborator
References
Development of a Patient-Derived 3D Immuno-Oncology Platform to Potentiate Immunotherapy Responses in Ascites-Derived Circulating Tumor Cells. [2023]High-grade serous ovarian cancer (HGSOC) is responsible for the majority of gynecology cancer-related deaths. Patients in remission often relapse with more aggressive forms of disease within 2 years post-treatment. Alternative immuno-oncology (IO) strategies, such as immune checkpoint blockade (ICB) targeting the PD-(L)1 signaling axis, have proven inefficient so far. Our aim is to utilize epigenetic modulators to maximize the benefit of personalized IO combinations in ex vivo 3D patient-derived platforms and in vivo syngeneic models. Using patient-derived tumor ascites, we optimized an ex vivo 3D screening platform (PDOTS), which employs autologous immune cells and circulating ascites-derived tumor cells, to rapidly test personalized IO combinations. Most importantly, patient responses to platinum chemotherapy and poly-ADP ribose polymerase inhibitors in 3D platforms recapitulate clinical responses. Furthermore, similar to clinical trial results, responses to ICB in PDOTS tend to be low and positively correlated with the frequency of CD3+ immune cells and EPCAM+/PD-L1+ tumor cells. Thus, the greatest response observed with anti-PD-1/anti-PD-L1 immunotherapy alone is seen in patient-derived HGSOC ascites, which present with high levels of systemic CD3+ and PD-L1+ expression in immune and tumor cells, respectively. In addition, priming with epigenetic adjuvants greatly potentiates ICB in ex vivo 3D testing platforms and in vivo tumor models. We further find that epigenetic priming induces increased tumor secretion of several key cytokines known to augment T and NK cell activation and cytotoxicity, including IL-6, IP-10 (CXCL10), KC (CXCL1), and RANTES (CCL5). Moreover, epigenetic priming alone and in combination with ICB immunotherapy in patient-derived PDOTS induces rapid upregulation of CD69, a reliable early activation of immune markers in both CD4+ and CD8+ T cells. Consequently, this functional precision medicine approach could rapidly identify personalized therapeutic combinations able to potentiate ICB, which is a great advantage, especially given the current clinical difficulty of testing a high number of potential combinations in patients.
Recurrent ovarian cancer: treatment with pegylated liposomal doxorubicin; a Westmead Cancer Care Centre experience. [2018]To describe the overall survival, progression-free survival, response rate and toxicity of pegylated liposomal doxorubicin (PLD) in recurrent ovarian cancer.
Phase I dose and sequencing study of pegylated liposomal doxorubicin and docetaxel in patients with advanced malignancies. [2018]Pegylated liposomal doxorubicin (PEG-LD) and docetaxel have single-agent activity in several malignancies. The authors conducted a Phase I trial to evaluate the maximum tolerated dose (MTD), toxicities, and effect of dose sequencing of this combination in patients with advanced malignancies.
A randomized phase III study evaluating pegylated liposomal doxorubicin versus capecitabine as first-line therapy for metastatic breast cancer: results of the PELICAN study. [2018]The PELICAN trial evaluates for the first time efficacy and safety of pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line treatment of metastatic breast cancer (MBC).
Doxorubicin-Loaded Platelet Decoys for Enhanced Chemoimmunotherapy Against Triple-Negative Breast Cancer in Mice Model. [2023]Triple-negative breast cancer (TNBC) is a highly aggressive subtype with a poor prognosis. Current single-agent checkpoint therapy has limited effectiveness in TNBC patients. In this study, we developed doxorubicin-loaded platelet decoys (PD@Dox) for chemotherapy and induction of tumor immunogenic cell death (ICD). By combining PD-1 antibody, PD@Dox has the potential to enhance tumor therapy through chemoimmunotherapy in vivo.
Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials. [2020]Antibodies targeting the programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) checkpoint may cause adverse events (AEs) that are linked to the mechanism of action of this therapeutic class and unique from those observed with conventional chemotherapy.
Bystander effect of antibody-drug conjugates: fact or fiction? [2022]Summarizing the current preclinical and clinical evidence about bystander effect of antibody-drug conjugates (ADCs) in solid tumors.
Strategies for Mitigating Antibody-Drug Conjugate Related Adverse Events for Precision Therapy. [2022]Antibody-drug conjugates (ADCs) have been revolutionary in improving personalized therapy of cancer. Through combining monoclonal antibodies, which are targeted to tumor-specific antigens, and cytotoxic agents, ADCs lead to selective delivery of active components, also called payloads, to cancerous cells while sparing healthy body cells from possible collateral damage. Adverse events, however, can still develop because of early release of the payload or cross-expression of targets by normal cells leading to collateral damage. In this review, we elaborate on the common and serious adverse events for the currently US Food and Drug Administration-approved ADCs in solid tumors and discuss mitigating strategies and dose modification guidance for optimizing efficacy and toxicity.
Efficacy, safety and tolerability of drugs studied in phase 3 randomized controlled trials in solid tumors over the last decade. [2021]Data suggest that for newly approved cancer drugs safety and tolerability are worse than in control arms of registration trials. Less is known about the balance between efficacy and toxicity of drugs studied in unselected phase 3 randomized controlled trials (RCTs) including those not resulting in regulatory approval. We searched Clinicaltrials.gov to identify phase 3 RCTs in patients with advanced breast, colorectal, lung, or prostate cancer completed between January 2005 and October 2016. We extracted efficacy and safety data from publications. For efficacy hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) were extracted. For safety, we computed odds ratios (ORs) and 95% confidence intervals (CIs) for toxic death, treatment discontinuation without progression and commonly reported grade 3/4 adverse events (AEs). Data were then pooled in a meta-analysis. Of 377 RCTs identified initially, 143 RCTs comprising 88,603 patients were included in the analysis. Of these, 79 (57%) trials met their primary endpoint. Compared to control groups, both PFS (HR 0.80; 95% CI 0.78-0.82) and OS (HR 0.87; 95% CI 0.85-0.89) were improved with experimental drugs. Toxic death (OR 1.14; 95% CI 1.03-1.27), treatment discontinuation without progression (OR 1.64; 95% CI 1.56-1.71) and grade 3/4 AEs were also more common with experimental drugs compared to respective control group therapy. Just over half of phase 3 RCTs in common solid tumors met their primary endpoint and in nearly half, experimental therapy had worse safety compared to control arms.
Olaparib dose re-escalation in ovarian cancer patients who experienced severe and/or uncommon adverse events: A case series. [2021]Few real-world studies have reported detailed management and dose adjustment strategies of adverse events (AEs) of ovarian cancer (OC) patients treated with the poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib. This case series aimed to describe olaparib AEs in Chinese OC patients in real-life settings and to explore dose modification strategies.