PRO1184 for Cancer
(PRO1184-001 Trial)
Recruiting in Palo Alto (17 mi)
+42 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Genmab
Must be taking: Platinum-based chemotherapy
Must not be taking: Strong CYP3A inhibitors
Disqualifiers: Interstitial lung disease, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This study will test the safety, including side effects, and determine the characteristics of a drug called Rina-S in participants with solid tumors.
Participants will have solid tumor cancer that has spread through the body (metastatic) or cannot be removed with surgery (unresectable).
Do I have to stop taking my current medications for the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use a strong CYP3A inhibitor within 14 days before starting the trial. It's best to discuss your current medications with the trial team.
What data supports the idea that PRO1184 for Cancer is an effective treatment?
The available research does not provide specific data on the effectiveness of PRO1184 for Cancer. Instead, it discusses other treatments like irinotecan combined with nedaplatin for cervical cancer, showing a response rate of 40% in initial treatment and 75% in recurrent cases. Without direct data on PRO1184, we cannot compare its effectiveness to these treatments.
12345What safety data is available for PRO1184 (Rinatabart Sesutecan, Rina-S) in cancer treatment?
The provided research does not contain specific safety data for PRO1184, Rinatabart Sesutecan, or Rina-S. The studies focus on irinotecan and its combinations with other drugs, assessing their efficacy and toxicity in various cancers. Adverse events such as leukopenia, thrombocytopenia, and vomiting were noted in some studies, but these are related to irinotecan-based treatments, not PRO1184.
12678Is the drug PRO1184 (Rinatabart Sesutecan, Rina-S) a promising treatment for cancer?
The drug PRO1184, also known as Rinatabart Sesutecan or Rina-S, is considered promising for cancer treatment because it is designed to target cancer cells more effectively, potentially leading to better outcomes with fewer side effects compared to existing treatments.
19101112Eligibility Criteria
This trial is for adults with certain advanced solid tumors, including specific types of ovarian, endometrial, lung, and breast cancers or mesothelioma that have spread (metastatic) or can't be removed by surgery. Participants must have measurable disease, adequate organ function, an ECOG performance status of 0 or 1 (which means they are fully active or restricted in physically strenuous activity but ambulatory), and agree to provide a tumor sample.Inclusion Criteria
My cancer is confirmed and cannot be removed by surgery.
I have received treatments known to help my condition.
My tumor shows folate receptor alpha expression.
+4 more
Exclusion Criteria
I have not had any other cancer in the last 3 years.
I do not have active brain metastases, but treated and stable ones are okay.
I have not had a severe infection in the last 2 weeks.
+3 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
Participants receive Rina-S monotherapy in escalating doses to evaluate safety and determine the recommended dose
Up to 1 year
Tumor-Specific Monotherapy
Participants receive Rina-S at the recommended dose for tumor-specific expansion cohorts
Up to 1 year
Combination Therapy
Participants receive Rina-S in combination with other drugs such as carboplatin, bevacizumab, or pembrolizumab
Up to 1 year
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 2 years
Participant Groups
The study tests PRO1184's safety and optimal dosing in part A; part B assesses its effectiveness at the determined dose/schedule. It targets patients whose cancer has either metastasized or is unresectable. The drug's characteristics will be evaluated through participants' responses.
4Treatment groups
Experimental Treatment
Group I: Part D3Experimental Treatment2 Interventions
Rina-S in combination with pembrolizumab
Group II: Part D2Experimental Treatment2 Interventions
Rina-S in combination with bevacizumab
Group III: Part D1Experimental Treatment2 Interventions
Rina-S in combination with carboplatin
Group IV: Part A, B, CExperimental Treatment1 Intervention
Rina-S monotherapy in escalating doses in Part A and at the recommended dose in Part B and C.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mary Crowley Cancer ResearchDallas, TX
Karmanos Cancer InstituteDetroit, MI
University of California Los Angeles Medical CenterLos Angeles, CA
Dana Farber Cancer InstituteBoston, MA
More Trial Locations
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Who Is Running the Clinical Trial?
GenmabLead Sponsor
ProfoundBio US Co.Lead Sponsor
References
[Combined irinotecan (CPT-11) and nedaplatin (254-S) therapy for advanced and/or recurrent cervical cancer]. [2018]We performed combination therapy with irinotecan (CPT-11) plus nedaplatin (254-S) for patients with cervical cancer. A total of 9 patients with cervical cancer (5 patients treated in neoadjuvant setting and 4 patients for recurrent disease) were administered 80 mg/m(2) of 254-Sintravenously on day 1 and 50 mg/m(2) of CPT-11 intravenously on day 1, 8 and 15. Treatment was repeated every 4 weeks. The average number of courses administered was 3.8 (range, 2-6). Grade 3 or 4 adverse events were leukopenia in 4 patients, thrombocytopenia in 1 patient and vomiting in 1 patient. The response rate was 40% in the neoadjuvant setting (2 PRs) and 75% in recurrent disease (3 PRs).
[Experimental study of effect of epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in combination with irinotecan]. [2018]To assess the optimal regimen and its mechanism of ZD1839 in combination with SN38, the active metabolite of irinotecan (CPT-11), in the colon cancer cell lines HT-29 and LoVo.
A phase 2 study of panitumumab with irinotecan as salvage therapy in chemorefractory KRAS exon 2 wild-type metastatic colorectal cancer patients. [2021]Targeted agents are standard treatment for RAS wild-type metastatic colorectal cancer in the first- and second-line settings. This phase 2 study determined the benefit of targeting the epidermal growth factor receptor (EGFR) with panitumumab plus irinotecan in irinotecan-refractory patients.
Phase I trial of the combination of irinotecan, paclitaxel, and carboplatin in patients with advanced non-small-cell lung cancer. [2018]To determine the maximum-tolerated dose, toxicities, and dose suitable for phase II/III trials of irinotecan (CPT-11) combined with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer (NSCLC).
Combination of irinotecan (CPT-11) and nedaplatin (NDP) for recurrent patients with uterine cervical cancer. [2021]The clinical activity of combination of irinotecan (CPT-11) and nedaplatin (NDP) for recurrent patients with uterine cervical cancer was evaluated retrospectively.
Efficacy of combination chemotherapy using irinotecan and nedaplatin for patients with recurrent and refractory endometrial carcinomas: preliminary analysis and literature review. [2019]We aimed to retrospectively evaluate the efficacy and toxicity of an irinotecan hydrochloride (CPT) and nedaplatin (N) combination therapy for recurrent and refractory endometrial carcinoma, administered based on UGT1A1 genotype.
First-line treatment with irinotecan and raltitrexed in metastatic colorectal cancer. Mature results of a multicenter phase II study. [2018]The combination of irinotecan and raltitrexed is safe and active in 5-fluorouracil-refractory, metastatic colorectal cancer (CRC), with the advantage of its convenient three-weekly schedule. The aim of this multicenter phase II study was to assess its efficacy and toxicity in first-line treatment.
Irinotecan: a new antineoplastic agent for the management of colorectal cancer. [2018]To review the pharmacologic, pharmacokinetic, therapeutic, and safety aspects of irinotecan, a new antineoplastic agent, and to assess its role in the treatment of colorectal and lung cancer.
Phase I-II study of irinotecan (CPT-11) plus nedaplatin (254-S) with recombinant human granulocyte colony-stimulating factor support in patients with advanced or recurrent cervical cancer. [2022]Combination chemotherapy with irinotecan (CPT-11) and platinum compounds is effective for treating cervical cancer. Nedaplatin (254-S) is a new cisplatin analogue that achieves a high response rate (53%) in patients with primary cervical cancer. We performed a phase I-II study of combination chemotherapy with CPT-11 plus 254-S for advanced or recurrent cervical cancer. The inclusion criteria were stage IV disease or recurrence. CPT-11 and 254-S were administered intravenously on day 1, while rhG-CSF (50 microg) was given on days 3-12. This regimen was repeated after 4 weeks. Dose escalation was carried out in tandem (CPT-11/254-S: 50/70, 50/80, and 60/80 mg m(-2)). A total of 27 patients (stage IV=seven, recurrence=20) were enrolled. The phase I study enrolled eight patients. At dose levels 1 and 2, no dose-limiting toxicities were observed. At dose level 3, the first two patients developed DLTs. The maximum tolerated dose of CPT-11 and 254-S was 60 and 80 mg m(-2), respectively, and the recommended doses were 50 and 80 mg m(-2). Grade 3/4 haematologic toxicity occurred in 67% in phase II study, but there were no grade 3 non-haematologic toxicities except for nausea or lethargy. In all 27 patients, there were two complete responses (7%) and 14 Partial responses (52%), for an overall response rate of 59% (95% confidence interval: 39-78%). Among the 12 responders with recurrent disease, the median time to progression and median survival were 161 days (range: 61-711 days) and 415 days (range: 74-801 days). This new regimen is promising for cervical cancer.
Design, Synthesis, and Evaluation of Glucose Transporter Inhibitor-SN38 Conjugates for Targeting Colorectal Cancer. [2023]Irinotecan (1), a prodrug of SN38 (2) approved by the US Food and Drug Administration for treating colorectal cancer, lacks specificity and causes many side effects. To increase the selectivity and therapeutic efficacy of this drug, we designed and synthesized conjugates of SN38 and glucose transporter inhibitors (phlorizin (5) or phloretin (6)), which could be hydrolyzed by glutathione or cathepsin to release SN38 in the tumor microenvironment, as a proof of concept. These conjugates (8, 9, and 10) displayed better antitumor efficacy with lower systemic exposure to SN38 in an orthotopic colorectal cancer mouse model compared with irinotecan at the same dosage. Further, no major adverse effects of the conjugates were observed during treatment. Biodistribution studies showed that conjugate 10 could induce higher concentrations of free SN38 in tumor tissues than irinotecan at the same dosage. Thus, the developed conjugates exhibit potential for treating colorectal cancer.
The in vitro metabolism of irinotecan (CPT-11) by carboxylesterase and beta-glucuronidase in human colorectal tumours. [2018]Irinotecan (CPT-11) is a prodrug that is used to treat metastatic colorectal cancer. It is activated to the topoisomerase poison SN-38 by carboxylesterases. SN-38 is metabolized to its inactive glucuronide, SN-38 glucuronide. The aim of this study was to determine, the reactivation of SN-38 from SN-38 glucuronide by beta-glucuronidase may represent a significant pathway of SN-38 formation.
Altered irinotecan metabolism in a patient receiving phenytoin. [2019]The systemic exposure to the anticancer agent irinotecan (CPT-11) and its active metabolite SN-38 were 79 and 92% reduced, respectively, relative to literature data, by concomitant phenytoin therapy. This finding suggests that increased doses of CPT-11 should be given to patients treated simultaneously with these drugs, to achieve adequate levels of SN-38.