Phase 2 Pan-Tumor Trial of R-DXd for Advanced/Metastatic Solid Tumors

Korábbi kezelés

• Any of the following within the past 6 months prior to enrollment: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event. (eg, intestinal ischemia).
• Chronic steroid treatment (>10 mg/day prednisone [or equivalent]) with exceptions as noted in the protocol.
• History of other active malignancy within 3 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death (eg, 5-year OS rate >90%) and treated with expected curative outcome .
• Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE v 5.0, Grade ≤1 or baseline.
• Prior exposure to other CDH6-targeted agents or an ADC that consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, trastuzumab deruxtecan, datopotamab deruxtecan).

Más betegség

• Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection.
• Has active or uncontrolled HIV, HBV or HCV infection.
• Uncontrolled or significant cardiovascular disease as specified in the protocol.
• Has a history of (noninfectious) ILD/pneumonitis irrespective of steroid use, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.

Egyéb

• Clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis.
• Clinically severe pulmonary compromise

• Adults ≥18 years of age on the day of signing the ICF. Follow local regulatory requirements if the legal age of consent for trial participation is >18 years old.
• Additional inclusion criteria for urothelial cancer cohort a. Pathologically or cytologically documented unresectable or metastatic urothelial carcinoma of the bladder, renal pelvis, ureter, or urethra. Histological variants are allowed if urothelial histology is predominant. b. Relapsed or progressed after treatment with ≥1 prior line of therapy (maximum of 3) that contains anti-PD-(L)1 therapy in the perioperative or metastatic setting.
• Additional inclusion criterion for the ccRCC cohort a. Pathologically or cytologically documented unresectable or metastatic ccRCC that was previously treated with no more than 3 prior systemic regimens for locally advanced or metastatic RCC, including both a PD-(L)1 checkpoint inhibitor and a VEGF-TKI in sequence or in combination.
• Additional inclusion criterion for the ccRCC cohort a. Pathologically or cytologically documented unresectable or metastatic ccRCC that was previously treated with no more than 3 prior systemic regimens for locally advanced or metastatic RCC, including both a PD-(L)1 checkpoint inhibitor and a VEGF-TKI in sequence or in combination.
• Participants must have at least 1 lesion, not previously irradiated, amenable to biopsy, and must consent to provide a pre-treatment biopsy from a primary and/or metastatic lesion.
• Has at least 1 measurable lesion according to RECIST version 1.1 per investigator assessment.
• Participants must have progressed radiologically on or after their most recent line of systemic therapy.
• Adequate organ/bone marrow function
• Additional inclusion criteria for endometrial cancer cohort a. Pathologically or cytologically documented endometrial cancer (carcinoma of any histological subtype or carcinosarcoma), irrespective of MSI or mismatch repair status; small cell/neuroendocrine tumors are not allowed even if mixed histology. b. Documented disease progression after having received ≥1 line of therapy (no more than 3), including PBC-containing systemic treatment and an anti-PD-(L)1 therapy containing regimen (combined or sequential) in the advanced/metastatic setting. Neo-adjuvant/adjuvant systemic therapies are counted as 1 line of therapy if there was progression or recurrence within 1 year from the final dose. • Prior hormonal therapy is not counted as a line of therapy in regard to the maximum allowed lines of treatment.
• Additional inclusion criteria for cervical cancer cohort a. Pathologically or cytologically documented recurrent or persistent squamous, adenosquamous, or adenocarcinoma of the uterine cervix. b. Disease progression after having received ≥1 prior line of therapy that includes systemic therapy in the advanced or metastatic setting. Neo-adjuvant/adjuvant systemic therapies are counted as 1 line of therapy if there was progression or recurrence within 1 year from the final dose.
• Additional inclusion criterion for non-HGSOC cohort a. Pathologically or cytologically documented unresectable or metastatic CCOC, low-grade endometrioid (Grade2 or lower), low-grade serous (Grade2 or lower), or mucinous OVC, from ovary, fallopian tube or peritoneum origin that was previously treated with at least 1 prior line of therapy. Neo-adjuvant/adjuvant systemic therapies are counted as 1 line of therapy if there was progression or recurrence within 1 year from the final dose. b. In Stage 3 only, participants with pathologically or cytologically documented unresectable or metastatic CCOC can be enrolled. Prior line of therapy requirements remains unchanged.