PRO1107 for Advanced Cancer
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: ProfoundBio US Co.
No Placebo Group
Trial Summary
What is the purpose of this trial?This is a global, open-label, multicenter Phase 1/2 study to evaluate the safety, tolerability, PK, and antitumor activity of PRO1107 in patients with advanced solid tumors. This study consists of 2 parts, Part A: dose escalation and dose level expansion, and Part B: tumor specific expansion.
What safety data is available for PRO1107 in advanced cancer treatment?The provided research does not contain specific safety data for PRO1107 or its variants. The studies mentioned focus on different treatments and methodologies, such as OPB-111077, which is a different compound, and the use of PRO-CTCAE for adverse event reporting. Therefore, no direct safety data for PRO1107 is available in the given research.34589
Is the drug PRO1107 a promising treatment for advanced cancer?Yes, PRO1107 is a promising treatment for advanced cancer because it is an antibody-drug conjugate (ADC), which combines the targeting ability of antibodies with the cancer-killing power of chemotherapy. This means it can deliver the treatment directly to cancer cells, potentially making it more effective and reducing harm to healthy cells.1261011
What data supports the idea that PRO1107 for Advanced Cancer is an effective treatment?The available research does not provide any data specifically about PRO1107 for Advanced Cancer. Instead, it focuses on other drugs like enzalutamide and apalutamide for prostate cancer. These studies show that enzalutamide, when combined with other therapies, improves survival and quality of life in prostate cancer patients. However, there is no information here about PRO1107's effectiveness.712131415
Do I need to stop my current medications for the trial?The trial protocol does not specify if you need to stop your current medications, but you cannot use a strong P450A CYP3A inhibitor within 2 weeks before starting the trial.
Eligibility Criteria
This trial is for adults with certain advanced solid tumors, including specific types of breast, ovarian, endometrial, gastroesophageal, bladder cancer and non-small cell lung cancer. Participants must have measurable disease after prior treatments and be in good physical condition (ECOG score 0 or 1). They also need to provide a tumor sample.Inclusion Criteria
I have been diagnosed with stomach or gastroesophageal junction cancer.
I have endometrial cancer, but it's not sarcoma.
My breast cancer is triple negative.
I have cancer in my stomach or where my esophagus meets my stomach.
I have been diagnosed with esophageal squamous cell carcinoma.
My cancer has spread, cannot be surgically removed, and has not responded to previous treatments.
I am fully active or can carry out light work.
My breast cancer is confirmed to be triple negative.
I am fully active or restricted in physically strenuous activity but can do light work.
My diagnosis is esophageal squamous cell carcinoma.
I have been diagnosed with ovarian, peritoneal, or fallopian tube cancer.
I have been diagnosed with endometrial cancer, not including sarcoma.
My condition is confirmed non-small cell lung cancer.
My cancer is in the bladder, ureter, or renal pelvis.
My cancer has spread, cannot be surgically removed, and has not responded to previous treatments.
My cancer is in the bladder, ureter, or renal pelvis.
I have ovarian, peritoneal, or fallopian tube cancer.
Exclusion Criteria
I have not had any other cancer in the last 3 years.
I have previously been treated with anti-PTK7 therapy.
My cancer progressed despite treatment with a specific drug (like vedotin).
Treatment Details
PRO1107 is being tested for safety and effectiveness against various advanced cancers. The study has two parts: Part A to find the right dose and expand it; Part B focuses on specific tumors. It's an open-label trial where everyone knows they're getting PRO1107.
1Treatment groups
Experimental Treatment
Group I: PRO1107Experimental Treatment1 Intervention
PRO1107 monotherapy in escalating doses in Part A and at the two recommended phase 2 doses in Part B
Find a clinic near you
Research locations nearbySelect from list below to view details:
HonorHealth Research InstituteScottsdale, AZ
The University of Texas MD Anderson Cancer CenterHouston, TX
Massachusetts General HospitalBoston, MA
START Mountain Cancer CenterSalt Lake City, UT
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Who is running the clinical trial?
ProfoundBio US Co.Lead Sponsor
GenmabLead Sponsor
References
Tumor necrosis factor-related apoptosis-inducing ligand's antitumor activity in vivo is enhanced by the chemotherapeutic agent CPT-11. [2018]Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in a wide variety of transformed human cells in vitro. In this study, the antitumor activity of recombinant TRAIL was analyzed in mice bearing human colon carcinoma tumors. We found that these tumors displayed a differential sensitivity to TRAIL in vivo that paralleled their susceptibility to TRAIL-induced apoptosis in vitro. Treatment of TRAIL-sensitive tumors 3 days after tumor challenge resulted in a dose-dependent inhibition of growth and the elimination of tumors in many mice. Colon carcinoma cell lines could be further sensitized to TRAIL-induced apoptosis in vitro by the addition of the chemotherapeutic agent camptothecin. Moreover, the combination of TRAIL and CPT-11, a water-soluble analogue of camptothecin, greatly enhanced the antitumor activity of TRAIL in vivo. TRAIL plus CPT-11 treatment of both 3- and 10-day established TRAIL-sensitive tumors resulted in both a significant inhibition of tumor growth and a high proportion of complete tumor regressions. Treatment of TRAIL-resistant tumors with TRAIL and CPT-11 dramatically slowed tumor growth and induced a transient tumor regression. These data demonstrate that TRAIL alone is a potent antitumor agent in vivo, and its activity can be significantly enhanced in combination with the chemotherapeutic agent CPT-11.
Effects of tumor necrosis factor-related apoptosis-inducing ligand alone and in combination with chemotherapeutic agents on patients' colon tumors grown in SCID mice. [2018]Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to induce apoptosis in a variety of malignant cell lines, but it shows little or no toxicity in most normal cells. We examined the response of three human colon tumors to TRAIL alone and in combination with chemotherapy, using SCID mice engrafted with intact patient surgical specimens. These tumors, taken from fresh surgical specimens, contained the heterogeneous tumor cell population characteristic of patient tumors and showed differential sensitivity to TRAIL alone. We also investigated the effect of TRAIL in combination with chemotherapy, using one tumor that showed moderate sensitivity to TRAIL alone. Combining TRAIL with either 5-fluorouracil (5-FU) or CPT-11 (irinotecan hydrochloride) produced a greatly enhanced antitumor effect over that of either agent alone, with 50% of the animals achieving complete tumor regression with a combination of TRAIL and CPT-11. By histological analysis, tumors treated with TRAIL plus either 5-FU or CPT-11 were seen to consist mainly of connective tissue and fibrotic areas with only a few scattered tumor cells encapsulated in the connective tissue. Several markers were assessed to investigate the basis for the observed therapeutic effect, and significant induction of apoptosis was observed in tumors treated with curative combinations. Cytoplasmic and cell surface expression of the TRAIL receptors DR4 and DR5 was observed in this patient's tumor by immunohistochemistry. Tumors treated with CPT-11 showed increased membrane expression of DR5, suggesting that CPT-11 may increase sensitivity to TRAIL by up-regulation of DR5. These results obtained in a relevant preclinical model support the idea that the use of TRAIL in combination with either 5-FU or CPT-11 may be an effective strategy in controlling human colon cancer.
Chemotherapy dose intensity reductions due to adverse drug reactions in an oncology outpatient setting. [2010]the aim of this study was to establish the incidence of adverse drug reactions (ADRs) that prevent administration of planned dose intensity antineoplastic chemotherapy in clinical practice.
Mode equivalence and acceptability of tablet computer-, interactive voice response system-, and paper-based administration of the U.S. National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). [2022]PRO-CTCAE is a library of items that measure cancer treatment-related symptomatic adverse events (NCI Contracts: HHSN261201000043C and HHSN 261201000063C). The objective of this study is to examine the equivalence and acceptability of the three data collection modes (Web-enabled touchscreen tablet computer, Interactive voice response system [IVRS], and paper) available within the US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system.
A First-in-Human Phase I Study of OPB-111077, a Small-Molecule STAT3 and Oxidative Phosphorylation Inhibitor, in Patients with Advanced Cancers. [2022]OPB-111077 is a novel inhibitor of STAT3 and mitochondrial oxidative phosphorylation that exhibited promising anticancer activity in preclinical models.In this first-in-human phase I study of OPB-111077 in unselected advanced cancers, treatment-emergent adverse events, most frequently nausea, fatigue, and vomiting, were generally mild to moderate in intensity and could be medically managed.Overall, only modest clinical activity was observed after OPB-111077 given as monotherapy. Notable antitumor activity was seen in a subject with diffuse large B-cell lymphoma.
Phase 1 study of PSMA ADC, an antibody-drug conjugate targeting prostate-specific membrane antigen, in chemotherapy-refractory prostate cancer. [2021]Prostate-specific membrane antigen (PSMA) is a well-characterized target that is overexpressed selectively on prostate cancer cells. PSMA antibody-drug conjugate (ADC) is a fully human IgG1 monoclonal antibody conjugated to the microtubule disrupting agent monomethyl auristatin E (MMAE), which is designed to specifically bind PSMA-positive cells, internalize, and then release its cytotoxic payload into the cells. PSMA ADC has demonstrated potent and selective antitumor activity in preclinical models of advanced prostate cancer. A Phase 1 study was conducted to assess the safety, pharmacokinetics, and preliminary antitumor effects of PSMA ADC in subjects with treatment-refractory prostate cancer.
Patient-reported outcomes following enzalutamide or placebo in men with non-metastatic, castration-resistant prostate cancer (PROSPER): a multicentre, randomised, double-blind, phase 3 trial. [2021]In the PROSPER trial, enzalutamide significantly improved metastasis-free survival in patients with non-metastatic, castration-resistant prostate cancer. Here, we report the results of patient-reported outcomes of this study.
Assessment of Adverse Events From the Patient Perspective in a Phase 3 Metastatic Castration-Resistant Prostate Cancer Clinical Trial. [2021]Standard adverse event (AE) reporting in oncology clinical trials has historically relied on clinician grading, which prior research has shown can lead to underestimation of rates of symptomatic AEs. Industry sponsors are beginning to implement in trials the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), which was developed to allow patients to self-report symptomatic AEs and improve the quality of symptomatic AE detection.
Dutch translation and linguistic validation of the U.S. National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™). [2020]The U.S. National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™) is a library of items for assessing symptomatic adverse events by patient self-report in oncology trials. The aim of this multi-site study was to generate and linguistically validate a Dutch language version of the U.S. PRO-CTCAE for use in the Netherlands and Dutch-speaking Belgium.
A phase Ib/II and pharmacokinetic study of EP0057 (formerly CRLX101) in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer. [2021]EP0057 (formerly CRLX101) is an investigational nanoparticle-drug conjugate (NDC) of a cyclodextrin-based polymer backbone plus camptothecin, a topoisomerase-1 inhibitor. Prior studies showed efficacy in recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer (EOC).
Antibody-drug conjugates: Resurgent anticancer agents with multi-targeted therapeutic potential. [2022]Antibody-drug conjugates (ADCs) constitute a relatively new group of anticancer agents, whose first appearance took place about two decades ago, but a renewed interest occurred in recent years, following the success of anti-cancer immunotherapy with monoclonal antibodies. Indeed, an ADC combines the selectivity of a monoclonal antibody with the cell killing properties of a chemotherapeutic agent (payload), joined together through an appropriate linker. The antibody moiety targets a specific cell surface antigen expressed by tumor cells and/or cells of the tumor microenvironment and acts as a carrier that delivers the cytotoxic payload within the tumor mass. Despite advantages in terms of selectivity and potency, the development of ADCs is not devoid of challenges, due to: i) low tumor selectivity when the target antigens are not exclusively expressed by cancer cells; ii) premature release of the cytotoxic drug into the bloodstream as a consequence of linker instability; iii) development of tumor resistance mechanisms to the payload. All these factors may result in lack of efficacy and/or in no safety improvement compared to unconjugated cytotoxic agents. Nevertheless, the development of antibodies engineered to remain inert until activated in the tumor (e.g., antibodies activated proteolytically after internalization or by the acidic conditions of the tumor microenvironment) together with the discovery of innovative targets and cytotoxic or immunomodulatory payloads, have allowed the design of next-generation ADCs that are expected to possess improved therapeutic properties. This review provides an overview of approved ADCs, with related advantages and limitations, and of novel targets exploited by ADCs that are presently under clinical investigation.
The impact of enzalutamide on quality of life in men with metastatic hormone-sensitive prostate cancer based on prior therapy, risk, and symptom subgroups. [2022]Enzalutamide plus androgen deprivation therapy (ADT) improved radiographic progression-free survival versus ADT alone in patients with metastatic hormone-sensitive prostate cancer (mHSPC) in ARCHES (NCT02677896). While health-related quality of life (HRQoL) was generally maintained in the intent-to-treat population, we further analyzed patient-reported outcomes (PROs) in defined subgroups.
Health-related quality of life with enzalutamide versus flutamide in castration-resistant prostate cancer from the AFTERCAB study. [2022]Patient-reported outcome (PRO) measures can provide valuable information in evaluating patients' health-related quality of life (HRQoL). Post hoc analysis of the AFTERCAB study was conducted to evaluate the HRQoL benefit of enzalutamide plus androgen deprivation therapy (ADT) compared to flutamide plus ADT for the treatment of patients with castration-resistant prostate cancer (CRPC) in Japan.
Apalutamide efficacy, safety and wellbeing in older patients with advanced prostate cancer from Phase 3 randomised clinical studies TITAN and SPARTAN. [2023]Apalutamide plus androgen-deprivation therapy (ADT) improved outcomes in metastatic castration-sensitive prostate cancer (mCSPC) and non-metastatic castration-resistant PC (nmCRPC) in the Phase 3 randomised TITAN and SPARTAN studies, respectively, and maintained health-related quality of life (HRQoL). Apalutamide treatment effect by patient age requires assessment.
Clinical Outcomes of Enzalutamide in Metastatic Hormone-sensitive Prostate Cancer in Patients Aged [2023]In ARCHES, treatment intensification of androgen deprivation therapy (ADT) with enzalutamide versus placebo improved clinical outcomes in metastatic hormone-sensitive prostate cancer (mHSPC). Understanding the benefits and tolerability of enzalutamide for men aged ≥75 yr may inform disease management.