study of anti-ceacam5 adc m9140 in participants with advanced solid tumors (proceade pantumor)

Conditions: Solid Tumors; Gastric Cancer; Non-Small Cell Lung Cancer (NSCLC); Pancreatic Cancer; Pancreatic Ductal Adenocarcinoma (PDAC)

Summary: the proceade pantumor study aims to investigate m9140 in multiple tumor types which express carcinoembryonic antigen-related cell adhesion molecule 5 (ceacam5) and it is therefore designed as a matrix study. this study aims to assess the antitumor activity, tolerability, safety, and pharmacokinetics (pk) of m9140 as monotherapy or in combination treatments in adult participants with locally advanced/metastatic ceacam5 expressing tumors. there will be 3 substudies under this master protocol that may be conducted in parallel. * proceade pantumor: a phase 1b/2, multicenter, open-label study of anti-ceacam5 antibody-drug conjugate m9140 in participants with advanced gastric cancer (substudy gc); * proceade pantumor: a phase 1b/2, multicenter, open-label study of anti-ceacam5 antibody-drug conjugate m9140 in participants with advanced non-small cell lung cancer (substudy nsclc); * proceade pantumor: a phase 1b/2, multicenter, open label study of anti-ceacam5 antibody-drug conjugate m9140 in participants with advanced pancreatic cancer (substudy pdac).

the study follows a master protocol concept with several separate substudies in specific indications. * substudy gc: the study duration per participant is on an average approximately 10 months. this includes a 28-day screening period, infusion (approximately 1 hour) on day 1 of every cycle, and safety follow-up visit 30 (± 3) days after the last dose of m9140. * substudy nsclc: study duration per participant is approximately 12 months. this includes a 28-day screening period, infusion (approximately 1 hour) on day 1 of every cycle, and safety follow-up visit 30 (± 3) days after the last dose of m9140. * substudy pdac: study duration per participant is on an average approximately 8 months. this includes a 28-day screening period, infusion (approximately 1 hour) on day 1 of every cycle, and safety follow-up visit 30 (±3) days after the last dose of m9140.

Eligibility criteria:
inclusion criteria: * participants are capable of signing informed consent as defined in protocol * eastern cooperative oncology group performance status (ecog ps) below or equal to 1 * participants with adequate hematologic, hepatic and renal function as defined in protocol * participant must have at least 1 lesion that is measurable using recist v1.1. * other protocol defined inclusion criteria could apply substudy gc: * participants in part a and part b with documented histopathological diagnosis of advanced or metastatic, her2 negative, gastric or gej (with an epicenter 2 centimeter (cm) proximal or distal to the gej) adenocarcinoma, who were intolerant/refractory to or progressed after systemic therapies for the advanced/metastatic stage that must have included (provided there is no medical contraindication and these agents are locally approved and available) a fluoropyrimidine and a platinum agent and an immune checkpoint inhibitors (ici) for participants with a known microsatellite instability-high (msi-h) status or participants whose tumor express pd-l1 with a cps greater than or equal (\>=) 1 * participants must have received and progressed (according to recist 1.1) on at least 1 line of therapy for the treatment of advanced/metastatic disease but no more than 2 * participants in part a with ceacam5high gc/gejc (defined as ihc \>= 2+ staining in \>= 50% of tumor cells) * participants in part b with ceacam5low gc/gejc (defined as ihc \>= 2+ staining in less than (\<) 50% of tumor cells) * other protocol defined inclusion criteria could apply substudy nsclc: * participants in part a and part b with histologically or cytologically documented advanced (stage iii not eligible for resection or curative radiation) or metastatic nsclc with or without driver genomic alterations * participants must have been intolerant/refractory to or progressed after systemic therapies for the advanced/metastatic stage * participants must have received and progressed (according to recist 1.1) on at least 1 line of therapy for the treatment of advanced/metastatic disease but no more than 3 * participants who received a platinum-containing regimen or a targeted therapy as (neo)-adjuvant therapy for early-stage disease, if relapse or metastases occurred during or within 3 months after regimen completion, are considered to have received a line of treatment in the advanced setting * participants in part a with ceacam5 high-expressing egfr tumors (including participants with any driver genomic alterations other than egfr mutations * participants in part b with ceacam5 high known egfr mutated tumors as assessed according to local clinical practice * other protocol defined inclusion criteria could apply substudy pdac: * participants with histologically or cytologically confirmed advanced or metastatic pdac, who were intolerant/refractory to or progressed after systemic therapies for the advanced metastatic stage that must have included (provided there is no medical contraindications, and these agents are locally approved and available; folfirinox regimen or nalirifnox regimen or nab-paclitaxel/gemcitabine regimen * participants must have received and progressed (according to recist 1.1) on at least one 1 line of therapy for the treatment of advanced/metastatic disease but no more than 2 * all participants will be screened using an ihc test to define ceacam5 expression. only participants with ceacam5high expressing tumors will be eligible * other protocol defined inclusion criteria could apply exclusion criteria: * participant has a history of malignancy within 3 years before the date of enrollment (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, benign prostate neoplasm/hypertropia, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years) * participants with known brain metastases, except those meeting the following criteria: brain metastases that have been treated locally and are clinically stable for at least 4 weeks prior to the start of treatment; no ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable) * participants with diarrhea (liquid stool) or ileus grade \> 1 * participants with active chronic inflammatory bowel disease (e.g., ulcerative colitis, crohn's disease, intestinal perforation) and/or bowel obstruction * cardiac arrhythmia, unstable angina, myocardial infarction, congestive heart failure (new york heart association \[nyha\] \>= ii) or a coronary revascularization procedure within 180 days of study entry. calculated qtc average (using the fridericia correction calculation) of \> 470 milliseconds (ms) * cerebrovascular accident/stroke (\< 6 months prior to enrollment) * other protocol defined exclusion criteria could apply substudy gc - participants with prior therapy with irinotecan substudy nsclc: - participants with prior therapy with irinotecan substudy pdac: none

Keywords: adc top1 inhibitor gastric cancer gastroesophageal junction cancer non-small cell lung cancer pancreatic cancer solid tumors