Rinatabart Sesutecan (Rina-S, PRO1184, GEN1184) for Advanced Solid Tumors (GCT1184-01/ PRO1184-001)

Launched by GENMAB · Oct 11, 2022

Keywords

ClinConnect Summary

This clinical trial is investigating a new drug called PRO1184 for patients with various types of advanced solid tumors, including different forms of ovarian, lung, and breast cancer. The main goal is to understand how safe the drug is and what side effects it may cause. Participants in the study will have cancer that has either spread to other parts of the body (metastatic) or cannot be surgically removed. The trial is currently looking for individuals aged 65 and older who have already received some form of treatment for their cancer.

To be eligible, participants should have a confirmed diagnosis of certain types of cancer and must have previously received treatments that have shown some benefits. They will also need to provide a tumor sample for analysis. Throughout the trial, participants will receive regular check-ups to monitor their health and how well the drug is working. It’s important to note that there are specific criteria regarding previous treatments and health conditions that potential participants need to meet. If you or a loved one is considering joining, this trial could offer an opportunity to access a new treatment while contributing to important research.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• Part A and B:
• • Histologically or cytologically confirmed metastatic or unresectable solid malignancy including ovarian cancer (must have epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer), endometrial cancer, non-small cell lung cancer (Part A), EGFR-mutated NSCLC (Part B), breast cancer (hormone receptor positive, HER2-negative and triple-negative) (Part A), mesothelioma.
• • Previously received therapies known to confer clinical benefit.
• • Measurable disease per RECIST v1.1 for all tumor types other than pleural mesothelioma which will use mRECIST v1.1 at baseline.
• Part C:
• • Participants must have histologically or cytologically confirmed metastatic or unresectable epithelial ovarian cancer as specified below.
• • High grade serous ovarian cancer, primary peritoneal cancer, or fallopian tube cancer (excluding endometrioid, clear cell carcinomas, mucinous, low grade, and those with a sarcomatous or neuroendocrine element)
• • Participants must have received 1 to 3 prior lines of therapy. Participants who had 1 to 4 prior lines of therapy are allowed if mirvetuximab soravtansine (MIRV) was the last line of therapy. Participants must have progressed radiographically on or after their most recent line of therapy.
• • Participants must have platinum-resistant ovarian cancer.
• • Participants must have received prior bevacizumab.
• • Participants with known or suspected deleterious germline or somatic BRCA mutations (as determined by Food and Drug Administration \[FDA\]-approved test in a Clinical Laboratory Improvement Amendments \[CLIA\]-certified laboratory) and who achieved a complete or partial response to platinum-based chemotherapy must have been treated with a poly ADP-ribose polymerase (PARP) inhibitor as maintenance treatment.
• • Participants must have known FRα status based on an FDA approved test. Those who are FRα positive must have previously received MIRV, unless the participant has a documented medical exception.
• • Participants who are FRα negative, in accordance with the FDA approved test (Ventana folate receptor \[FOLR1\] RxDx Assay), and were treated with MIRV, are excluded.
• • Measurable disease per the RECIST v1.1 at baseline.
• Part D:
• Cohort D1 (Rina-S+carboplatin):
• • Participants must have platinum-sensitive ovarian cancer.
• • Participants must have received 1 to 3 prior lines of therapy.
• Cohort D2 (Rina-S+bevacizumab):
• • Participants must have primary platinum-refractory, platinum-resistant, or platinum-sensitive ovarian cancer.
• • Participants with primary platinum-refractory ovarian cancer must have received ≤2 prior lines of therapy. Primary platinum-refractory ovarian cancer is defined as a lack of response or by progression within 91 days after completing front-line platinum containing therapy.
• • Participants must have received 1 to 3 prior lines of therapy for platinum-resistant ovarian cancer (PROC), and up to 4 prior lines of therapy for platinum-sensitive ovarian cancer (PSOC). Prior treatments may have included bevacizumab, PARP inhibitor, and MIRV.
• • Participants with PSOC must have disease progression on or after maintenance treatment, or at least 6 months (\>183 days) or more from the last dose of platinum-based therapy.
• Cohort D3 (Rina-S+pembrolizumab):
• • Endometrial cancer (any subtype excluding sarcoma).
• • Participants must have received prior platinum-based chemotherapy for recurrent or advanced disease.
• Part F:
• • Participants must have histologically or cytologically confirmed endometrial cancer as specified below.
• • Advanced, recurrent, metastatic, or primary unresectable endometrial cancer (any subtype excluding neuroendocrine tumors, carcinosarcoma, or endometrial sarcoma)
• * Participants must have received 1 to 3 prior lines of therapy in advanced, recurrent, or metastatic setting, and must have progressed radiographically on or after their most recent line of therapy:
• • Participants must have received prior platinum-based chemotherapy and a programmed death-ligand 1 (PD-\[L\])1 inhibitor.
• • Participants who progress \>12 months after completion of prior adjuvant or neoadjuvant platinum-based chemotherapy must receive 1 additional cytotoxic systemic treatment prior to enrollment in this study.
• • Hormonal therapy alone (i.e., without chemotherapy) will not be counted as a separate line of therapy.
• • Measurable disease per the RECIST Version 1.1 at baseline.
• Exclusion Criteria:
• • History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids within the past 2 years, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• • Use of a strong cytochrome P450 3A (CYP3A) inhibitor within 14 days (dose escalation only).
• • Prior therapy with a topoisomerase 1 inhibitor-based antibody drug conjugate.
• • Note: Other protocol-defined inclusion/exclusion may apply.