PRO1184 for Cancer

(RAINFOL-01 Trial)

Recruiting at 45 trial locations

Overseen By Genmab Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Genmab

Must be taking: Platinum-based chemotherapy

Must not be taking: Strong CYP3A inhibitors

Disqualifiers: Interstitial lung disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

569 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effects of a drug called Rina-S (also known as PRO1184) for individuals with metastatic or unresectable solid tumor cancers. Researchers are testing Rina-S alone and in combination with other medicines like carboplatin, bevacizumab, and pembrolizumab to determine the most effective approach. The trial seeks participants with specific cancers, such as ovarian, endometrial, or lung cancer, who have undergone previous treatments but need new options. Those with these cancers seeking new treatment possibilities might find this trial suitable. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Earlier studies found that treatment with Rinatabart Sesutecan (Rina-S) was generally well tolerated. Patients experienced manageable side effects, and no new safety issues emerged. This information comes from research where Rina-S was used alone and with other cancer drugs like carboplatin, bevacizumab, and pembrolizumab. Researchers are testing these combinations to potentially enhance the treatment's effectiveness. The studies have shown promising results, but as this trial remains in the early stages, further research is necessary to fully understand the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about PRO1184 for cancer because it offers a new approach by using Rina-S, either alone or in combination with other drugs like carboplatin, bevacizumab, or pembrolizumab. Unlike standard treatments that often target cancer cells broadly, Rina-S is designed to act more selectively, potentially reducing side effects and improving effectiveness. The combination with pembrolizumab is particularly promising, as it could enhance the immune system's ability to fight cancer cells. This innovative approach might offer better outcomes and a more personalized treatment option for patients.

What evidence suggests that this trial's treatments could be effective for solid tumor cancer?

Research has shown that Rina-S, also known as PRO1184, may help treat solid tumors. In this trial, some participants may receive Rina-S alone, which has been shown to shrink tumors in 50% of patients in certain studies. Others will receive Rina-S combined with carboplatin; one study found this combination helped shrink tumors in 55.6% of patients. Additionally, some participants will receive Rina-S with other drugs like bevacizumab or pembrolizumab, which also showed positive results in fighting tumors. Overall, Rina-S appears to control the disease in many patients, suggesting it could be effective for solid tumors. ^{1 2 4 6 7}

Who Is on the Research Team?

Study Official

Principal Investigator

Genmab

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• PRO1184

Trial Overview 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.

How Is the Trial Designed?

Group I: Part D3 Experimental Treatment 2 Interventions

Rina-S in combination with pembrolizumab

Group II: Part D2 Experimental Treatment 2 Interventions

Rina-S in combination with bevacizumab

Group III: Part D1 Experimental Treatment 2 Interventions

Rina-S in combination with carboplatin

Group IV: Part A, B, C, F and K Experimental Treatment 1 Intervention

Rina-S monotherapy in Part A and at the recommended dose in Parts B, C, F and K.

Who Is Running the Clinical Trial?

Genmab

Lead Sponsor

Trials

76

Recruited

15,300+

Dr. Jan van de Winkel

Genmab

Chief Executive Officer since 2010

PhD in Immunology, University of Utrecht

Dr. Judith Klimovsky

Genmab

Chief Medical Officer since 2019

MD, University of Copenhagen

ProfoundBio US Co.

Lead Sponsor

Trials

3

Recruited

750+

Published Research Related to This Trial

A phase I-II study involving 27 patients with advanced or recurrent cervical cancer showed that the combination of irinotecan (CPT-11) and nedaplatin (254-S) resulted in a promising overall response rate of 59%, with 7% achieving complete responses and 52% partial responses.

The maximum tolerated doses were determined to be 60 mg/m² for CPT-11 and 80 mg/m² for nedaplatin, with manageable toxicity; 67% of patients experienced grade 3/4 hematologic toxicity, but non-hematologic toxicities were mostly mild.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Tsuda, H., Hashiguchi, Y., Nishimura, S., et al.[2022]

The newly designed conjugates of SN38 with glucose transporter inhibitors showed improved antitumor efficacy and reduced systemic exposure compared to irinotecan in a mouse model of colorectal cancer.

These conjugates did not exhibit major adverse effects during treatment, indicating a safer profile while effectively delivering higher concentrations of the active drug in tumor tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design, Synthesis, and Evaluation of Glucose Transporter Inhibitor-SN38 Conjugates for Targeting Colorectal Cancer. Chiu, PF., Chang, CK., Huang, PS., et al.[2023]

The study found that beta-glucuronidase in tumor tissue can reactivate SN-38 from its inactive form, SN-38 glucuronide, suggesting that this pathway may significantly contribute to the effectiveness of irinotecan in treating metastatic colorectal cancer.

While the conversion rate of irinotecan to SN-38 was lower in tumor tissue compared to normal colon tissue, the activity of beta-glucuronidase was similar in both, indicating that tumors may still effectively produce SN-38 from SN-38 glucuronide, enhancing drug exposure in the tumor environment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The in vitro metabolism of irinotecan (CPT-11) by carboxylesterase and beta-glucuronidase in human colorectal tumours. Tobin, P., Clarke, S., Seale, JP., et al.[2018]

The study found that administering SN38 followed by ZD1839 in colon cancer cell lines resulted in a synergistic effect, enhancing the treatment's efficacy, while the reverse order led to antagonistic effects.

ZD1839 effectively inhibited EGFR phosphorylation without changing its expression, and it helped maintain SN38-induced DNA damage and apoptosis, suggesting a potential mechanism for improved therapeutic outcomes when using the sequential regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Experimental study of effect of epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in combination with irinotecan]. Xu, JM., Li, YM., Wang, Y., et al.[2018]

The irinotecan hydrochloride and nedaplatin (CPT-N) combination therapy showed a clinical benefit rate of 42.8% in 21 patients with recurrent endometrial carcinoma, indicating its potential effectiveness as a second- or third-line treatment.

Despite some patients experiencing grade 3 toxicities like neutropenia and diarrhea, these side effects were manageable and resolved with conservative treatment, suggesting that the CPT-N regimen is tolerable and a viable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of combination chemotherapy using irinotecan and nedaplatin for patients with recurrent and refractory endometrial carcinomas: preliminary analysis and literature review. Miyamoto, M., Takano, M., Kuwahara, M., et al.[2019]

Irinotecan is an effective treatment for advanced colorectal cancer, particularly as a first-line therapy and for patients who do not respond to fluorouracil-based treatments.

The drug also shows potential activity against lung cancer and other types of cancers, but it can cause significant side effects, including myelosuppression and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan: a new antineoplastic agent for the management of colorectal cancer. Cersosimo, RJ.[2018]

In a study involving 9 patients with cervical cancer, combination therapy using irinotecan and nedaplatin showed a 40% response rate in patients receiving treatment before surgery and a 75% response rate in those with recurrent disease.

While the treatment was effective, it also led to significant side effects, including grade 3 or 4 adverse events such as leukopenia in 4 patients, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combined irinotecan (CPT-11) and nedaplatin (254-S) therapy for advanced and/or recurrent cervical cancer]. Hiruma, R., Kamide, T., Anzai, N., et al.[2018]

The combination of irinotecan (CPT-11) and nedaplatin (NDP) showed a clinical response rate of 38.5% in 26 evaluable patients with recurrent uterine cervical cancer, indicating its potential efficacy as a treatment option.

However, the treatment was associated with significant hematological toxicity, with severe neutropenia and leukopenia occurring in 79.3% and 96.6% of cases, respectively, highlighting the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of irinotecan (CPT-11) and nedaplatin (NDP) for recurrent patients with uterine cervical cancer. Ohara, T., Kobayashi, Y., Yoshida, A., et al.[2021]

In a phase II study involving 62 previously untreated patients with metastatic colorectal cancer, the combination of irinotecan and raltitrexed showed a 30% overall response rate, indicating it is an active treatment option.

While the treatment was generally safe and administered on a convenient three-week schedule, significant toxicities were observed, including a 27% incidence of severe diarrhea and a 5% mortality rate due to treatment-related adverse events, suggesting that its efficacy and safety profile may not be optimal for first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line treatment with irinotecan and raltitrexed in metastatic colorectal cancer. Mature results of a multicenter phase II study. Aparicio, J., Vicent, JM., Maestu, I., et al.[2018]

In a phase 2 study involving 61 patients with irinotecan-refractory metastatic colorectal cancer, the combination of panitumumab and irinotecan resulted in a modest overall response rate of 15.2% among RAS wild-type patients, with a median progression-free survival of 3.8 months and median overall survival of 12.5 months.

The study found that while the treatment was feasible, it had limited efficacy, and no specific biomarkers were identified that could predict patient response to the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 study of panitumumab with irinotecan as salvage therapy in chemorefractory KRAS exon 2 wild-type metastatic colorectal cancer patients. Elez, E., Pericay, C., Valladares-Ayerbes, M., et al.[2021]

Concomitant therapy with phenytoin significantly reduces the systemic exposure to the anticancer drug irinotecan (CPT-11) and its active metabolite SN-38 by 79% and 92%, respectively.

To maintain effective levels of SN-38 in patients receiving both irinotecan and phenytoin, it may be necessary to increase the doses of irinotecan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Altered irinotecan metabolism in a patient receiving phenytoin. Mathijssen, RH., Sparreboom, A., Dumez, H., et al.[2019]

The study established that a combination of irinotecan (CPT-11) at 100 mg/m², paclitaxel at 175 mg/m², and carboplatin AUC 5 can be safely administered to patients with advanced non-small-cell lung cancer (NSCLC), with neutropenia and diarrhea identified as the main dose-limiting toxicities.

The treatment demonstrated a 39% objective tumor response rate, with a median survival of 11 months and a 1-year survival probability of 46%, indicating significant efficacy for this regimen in advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of the combination of irinotecan, paclitaxel, and carboplatin in patients with advanced non-small-cell lung cancer. Socinski, MA., Sandler, AB., Miller, LL., et al.[2018]

Citations

1. ir.genmab.com ir.genmab.com/news-releases/news-release-details/genmab-announces-new-data-demonstrating-investigational

Genmab Announces New Data Demonstrating ... In the 100 mg/m2 cohort, the confirmed ORR was 50.0%, including two CRs. Anti-tumor activity was also observed in patients treated with Rina-S ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05579366

NCT05579366 | Rinatabart Sesutecan (Rina-S, PRO1184 ... This study will test the safety, including side effects, and determine the characteristics of a drug called Rina-S in participants with solid tumors.

3. cancernetwork.com cancernetwork.com/view/rina-s-elicits-encouraging-antitumor-activity-in-advanced-ovarian-cancer

Rina-S Elicits Encouraging Antitumor Activity in Advanced ... Data showed a disease control rate (DCR) of 86.4% (95% CI, 65.1%-97.1%) and 88.9% (95% CI, 65.3%-98.6%) in each cohort. Rinatabart sesutecan ...

4. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_1/6880/759525/Abstract-6880-Rinatabart-sesutecan-PRO1184-in

Abstract 6880: Rinatabart sesutecan (PRO1184) in ... Here we evaluate the combinability and antitumor activity of Rina-S with standard-of-care (SOC) therapies in preclinical cancer models.

5. clin.larvol.com clin.larvol.com/trial-detail/NCT05579366

Rinatabart Sesutecan (Rina-S, PRO1184, GEN1184) for ... "The study showed that at a median study follow-up of one year, treatment with Rina-S 100 mg/m² every 3 weeks (Q3W) resulted in a 50.0% confirmed objective ...

6. ir.genmab.com ir.genmab.com/news-releases/news-release-details/investigational-rinatabart-sesutecan-rina-sr-continues-show

Investigational Rinatabart Sesutecan (Rina-S®) Continues ... The data are from the dose expansion cohort of the multi-part study evaluating the safety and efficacy of Rina-S as a single agent in solid ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06619236

NCT06619236 | Study to Assess the Efficacy of Rina-S ... The purpose of this study is to compare how well Rina-S works against platinum-resistant ovarian cancer compared to chemotherapy drugs that are already approved ...