Phase 1/2 Study of Rina-S in Patients With Locally Advanced and/or Metastatic Solid Tumors

Plain English Summary

Rinatabart Sesutecan (Rina-S, PRO1184, GEN1184) for Advanced Solid Tumors (GCT1184-01/ PRO1184-001) is a Phase 2 clinical trial sponsored by Genmab studying High Grade Epithelial Ovarian Cancer, High Grade Serous Ovarian Cancer, Primary Peritoneal Carcinoma, Fallopian Tube Cancer, Endometrial Cancer, Non-small Cell Lung Cancer, Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (NSCLC), Mesothelioma, Breast Adenocarcinoma, Triple Negative Breast Cancer. This trial is testing a new drug called Rina-S to see how safe it is and what effects it has on patients with advanced solid tumors. It is for adults with specific types of solid tumors that have spread or cannot be removed by surgery, including certain types of ovarian, lung, and breast cancers. Participation involves receiving Rina-S, potentially along with other standard treatments, and undergoing regular medical check-ups and tests. Alternative treatments may include chemotherapy, targeted therapy, or immunotherapy, depending on the specific cancer type and previous treatments. The trial aims to enroll 764 participants.

Official Summary

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).

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults with specific types of advanced or unresectable solid tumors, including certain ovarian, endometrial, lung, breast, and mesothelioma cancers. Patients must have had previous treatments that did not work or have stopped working. Specific criteria apply based on the type of cancer, previous therapies, and whether the cancer is resistant to platinum-based treatments. This trial is studying High Grade Epithelial Ovarian Cancer, High Grade Serous Ovarian Cancer, Primary Peritoneal Carcinoma, Fallopian Tube Cancer, Endometrial Cancer, Non-small Cell Lung Cancer, Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (NSCLC), Mesothelioma, Breast Adenocarcinoma, Triple Negative Breast Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures will tell us how safe Rina-S is, what side effects it causes, and how well it shrinks tumors or stops them from growing. The specific primary outcome measures are: Parts A, B, and D - Incidence of Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability] (Through end of treatment, up to approximately 1 year.); Parts A, and D - Dose Limiting Toxicity (DLT) (At the end of Cycle 1 (each cycle is 21 days)); Parts C, F, G, H, I, and J- Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR, Parts C, E, and F) or Investigator (Part G, I, and J) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Through end of treatment, up to approximately 1 year.); Part K (US Participants Only) - Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Findings by Holter (Cycles 1 to 3 (each cycle is 21 days)). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial is important because it explores a new treatment option for patients with advanced solid tumors who have limited or no other effective treatment choices. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets High Grade Epithelial Ovarian Cancer, High Grade Serous Ovarian Cancer, Primary Peritoneal Carcinoma, Fallopian Tube Cancer, Endometrial Cancer, Non-small Cell Lung Cancer, Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (NSCLC), Mesothelioma, Breast Adenocarcinoma, Triple Negative Breast Cancer, where improved treatment options are needed.

Investor Insight

This trial targets a significant unmet need in advanced solid tumors, potentially offering a new therapeutic option in a competitive market with a moderate probability of approval if safety and effica Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval. The large enrollment target of 764 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor about the specific Rina-S treatment plan for your cancer type and what to expect regarding side effects. Be prepared for regular visits for drug infusions, blood tests, scans to monitor your cancer, and to report any new symptoms or side effects. Understand that this is an investigational drug, meaning its full effects and risks are still being studied. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 764 participants

Interventions

• DRUG: Rina-S — Intravenous infusion of Rina-S
• DRUG: Carboplatin — Carboplatin intravenous infusion
• DRUG: Bevacizumab — Bevacizumab intravenous infusion
• DRUG: Pembrolizumab — Pembrolizumab intravenous infusion

Primary Outcomes

• Parts A, B, and D - Incidence of Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability] (Through end of treatment, up to approximately 1 year.)
• Parts A, and D - Dose Limiting Toxicity (DLT) (At the end of Cycle 1 (each cycle is 21 days))
• Parts C, F, G, H, I, and J- Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR, Parts C, E, and F) or Investigator (Part G, I, and J) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Through end of treatment, up to approximately 1 year.)
• Part K (US Participants Only) - Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Findings by Holter (Cycles 1 to 3 (each cycle is 21 days))

Secondary Outcomes

• Parts A, B, and D - Best Overall Response (BOR) (Up to approximately 1 year.)
• Parts A, B, and D - ORR (Up to approximately 1 year.)
• Parts A, B, and D - Disease Control Rate (DCR) (Up to approximately 1 year.)
• Parts A, B, C, D, F, G, H, I, and J - Progression-Free Survival (PFS) (Through end of treatment, up to approximately 1 year.)
• Parts C, F, G, H, I and J - Overall survival (OS) (Up to approximately 2 years.)

Full 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 or cervical cancer (Part B).
* 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 and H:

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 up to 3 prior lines of therapy. Participants may have had up to to 4 prior lines of therapy are allowed if MIRV is locally approved and was used as 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 or approved biosimilar.
* 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; or locally approved equivalent) 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.
* Measurable disease per the RECIST v1.1 at baseline.

Part D:

Cohort D1:

* Participants must have platinum-sensitive ovarian cancer.
* Participants must have received 1 to 3 prior lines of therapy.

Cohort D2:

* 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 and D4:

• Endometrial cancer (any subtype excluding sarcoma).

Part F and G:

* Participants must have histologically or cytologically confirmed EC.
* Recurrent progressive EC (any subtype excluding neuroendocrine tumors, carcinosarcoma, or endometrial sarcoma) following prior therapy.
* Participants must have received 1 to 3 prior lines of therapy, 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.

Part I:

* Participants must have histologically or cytologically confirmed high grade serous or endometrioid epithelial ovarian cancer, fallopian tube cancer and primary peritoneal cancer (excluding clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies or low grade/borderline ovarian tumors).
* Participants must have platinum sensitive ovarian cancer.
* Measurable disease per the RECIST Version 1.1 at baseline.

Part J:

* Participants must have high grade epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer including serous, endometrioid, and clear cell carcinomas, and excluding mucinous, low grade, and those with a sarcomatous or neuroendocrine element.
* Measurable disease per the RECIST Version 1.1 at baseline.

Part K:

* Participants must have histologically or cytologically confirmed metastatic or unresectable ovarian cancer (must have high grade epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer including serous, endometrioid, and clear cell carcinomas, and excluding muc

Trial Locations

• USOR HonorHealth, Phoenix, Arizona, United States
• USOR Arizona Oncology Associates, Tucson, Arizona, United States
• University of California Los Angeles Medical Center, Los Angeles, California, United States
• University of California, San Diego; Moores Cancer Center, San Diego, California, United States
• USOR Sansum Clinic, Santa Barbara, California, United States
• Providence Medical Foundation, Santa Rosa, California, United States
• USOR Florida Cancer Specialists South, Fort Myers, Florida, United States
• USOR Florida Cancer Specialists North, St. Petersburg, Florida, United States
• USOR Florida Cancer Specialists East, West Palm Beach, Florida, United States
• Augusta University Georgia Cancer Center, Augusta, Georgia, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Ovarian Cancer
• Endometrial Cancer
• Non-Small Cell Lung Cancer
• Breast Cancer
• Mesothelioma
• Cervical Cancer
• Solid Tumors
• Metastatic Cancer
• Advanced Cancer
• Recurrent Cancer

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