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

Genmab

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Hormone Receptor-positive/Her2 Negative Breast Cancer; High Grade Serous Ovarian Cancer; High Grade Epithelial Ovarian Cancer; Fallopian Tube Cancer; Platinum Sensitive Ovarian Cancer (PSOC); Endometrial Cancer; Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (NSCLC); Primary Peritoneal Carcinoma; Non-small Cell Lung Cancer; Platinum-Resistant Ovarian Cancer; Breast Adenocarcinoma; Mesothelioma; Triple Negative Breast Cancer

Treatments: Drug: Carboplatin; Drug: Pembrolizumab; Drug: Rina-S; Drug: Bevacizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05579366

CTR20230813 (Registry Identifier)

PRO1184-001

GCT1184-01 (Other Identifier)

Details and patient eligibility

About

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).

Full description

This is a Phase 1/2 study of Rina-S; also known as GEN1184, a folate receptor alpha (FRα) targeted antibody-drug conjugate, to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of Rina-S in participants with selected locally advanced and/or metastatic solid tumors, including epithelial ovarian cancer, endometrial cancer, breast cancer, non-small cell lung cancer, and mesothelioma.

The study consists of multiple parts:

Part A: dose-escalation cohorts

Part B: tumor-specific monotherapy dose-expansion cohorts

Part C: platinum-resistant ovarian cancer (PROC) cohort

Part D: combination therapy cohorts

Participants will continue to receive study treatment until the first instance of disease progression, unacceptable toxicity, investigator decision, consent withdrawal, study termination by the Sponsor, pregnancy, or death.

Enrollment: 404 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 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.
• Prior induction plus maintenance is considered 1 line of therapy, even if parts of the treatment regimen (induction or maintenance) are interrupted and/or resumed at a later date, in the absence of disease progression while on active treatment.
• A switch/change in regimen due solely to toxicity or participant preference (and not disease progression) is not considered a separate line of therapy.

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 platinum-refractory, platinum-resistant, or platinum-sensitive ovarian cancer.
• 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.

Cohort D3 (Rina-S+pembrolizumab):

• Endometrial cancer (any subtype excluding sarcoma).
• Participants must have received prior platinum-based chemotherapy for recurrent or advanced disease.

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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404 participants in 4 patient groups

Part A, B, C

Experimental group

Description:

Rina-S monotherapy in escalating doses in Part A and at the recommended dose in Part B and C.

Treatment:

Drug: Rina-S

Part D1

Experimental group

Description:

Rina-S in combination with carboplatin

Treatment:

Drug: Rina-S

Drug: Carboplatin

Part D2

Experimental group

Description:

Rina-S in combination with bevacizumab

Treatment:

Drug: Bevacizumab

Drug: Rina-S

Part D3

Experimental group

Description:

Rina-S in combination with pembrolizumab

Treatment:

Drug: Rina-S

Drug: Pembrolizumab