RecruitingPhase 1 / Phase 2

A Clinical Study to Test if an Investigational Treatment Called BNT326 is Safe and Potentially Beneficial When Used Alone or in Combination With Other Investigational Treatments Such as BNT327, for People With Advanced Malignant Tumors

A Phase I/II, Open-label, Adaptive Two-part Trial to Evaluate the Safety, Efficacy, Optimal Dose and Pharmacokinetics of BNT326 as Monotherapy and in Combination With Cancer Immunotherapies in Participants With Advanced Solid Tumors

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Time periods mentioned: 24 months

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "Study treatment will be continued for up to 24 months or until disease progression, withdrawal of consent, termination of the study by the sponsor, or unacceptable toxicity."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests BNT326 alone or with other study treatments, such as BNT327, in adults with advanced solid cancers. It checks safety, how well treatment works, the best dose, and how the body handles BNT326. It is for people whose cancer has spread, returned, or grown after treatment.

This study will evaluate the safety, efficacy, optimal dose, and pharmacokinetics (PK) of BNT326 as monotherapy (Part 1) and as combination treatment with immunotherapeutic agents (Part 2) in participants with histologically or cytologically confirmed solid tumors that are advanced (i.e., either metastatic or recurrent tumors with no further definitive treatment possible) and/or have relapsed/progressed after prior therapy.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be at least 18 years old, or older if local consent laws require it.
  • Have advanced cancer confirmed by tissue or cell tests, or clear growth of a cancer tested before.
  • Have cancer that can be measured on scans.
  • Be fully active or able to walk and do light work.
  • Have organs and bone marrow working well enough, based on tests within 7 days before joining or being assigned treatment.
  • Have a cancer type allowed in a study group. These include certain melanomas, lung, breast, stomach, colon, rectal, cervical, bile duct, gallbladder, liver, kidney, uterine lining, pancreatic, and neuroendocrine cancers.
  • Meet your group's cancer test rules. Some groups require certain gene changes or protein test results, such as EGFR changes in lung cancer or HER2-negative breast cancer.
  • Meet your group's past treatment rules. Many groups require cancer to have grown after certain treatments, or treatment to have stopped because of side effects. Limits on the number and types of past treatments vary by group.

Who can't join

  • Past inability to tolerate a topoisomerase I inhibitor, a type of cancer drug, or a treatment carrying one of these drugs. Examples include topotecan, irinotecan, and deruxtecan.
  • An uncontrolled illness that makes the study unsafe or makes it hard to follow study steps. Listed examples include a bleeding disorder, active bleeding, or an active infection.
  • The supplied exclusion list cuts off, so more exclusions may apply.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

Key Inclusion Criteria (applicable to all participants and all parts unless otherwise specified): * Aged ≥18 years at the time of giving informed consent. Local laws will be followed if the age of consent is older. * Have histologic or cytologic documented advanced disease, either at relapse or upon diagnosis of metastatic disease. This requirement may be considered met when advanced disease derives from unequivocal progression of a previously biopsied site of disease (e.g., progression of residual tumor after concomitant chemo-radiation for Stage III NSCLC). * Have measurable disease defined by RECIST v1.1. * Have ECOG performance status of 0 or 1. * Have adequate organ and bone marrow function (as specified in the protocol) within 7 days before randomization/enrollment. * Cohort 1A: * Have histologically or cytologically confirmed diagnosis of unresectable or metastatic cutaneous melanoma not amenable to local therapy. * Participants must have previously received a PD-1 or PD-L1 inhibitor, and, for participants with human gene that encodes a protein called B-Raf (BRAF) gene mutant melanoma, a prior treatment regimen that included vemurafenib, dabrafenib, or another BRAF gene inhibitor with or without mitogen-activated protein kinase protein inhibitor, if available and clinically indicated per local standard of care (SoC) and have experienced progression during or after the previous treatment or discontinued from prior therapy due to intolerance. * Cohort 1B and 1C: Have advanced (i.e., metastatic or locally recurrent where local therapy with curative intent is not possible) non-squamous or squamous NSCLC. * Cohort 1B: * Have no actionable genomic alterations, such as EGFR mutations, anaplastic lymphoma kinase rearrangements, or other genomic alterations for which targeted molecular therapies are available. For enrolled participants with predominantly squamous histology tumors, molecular testing will not be required in cases where it is not part of the SoC. * Have experienced relapse or progression during or after treatment with standard systemic therapy including platinum-based chemotherapy and/or immune checkpoint inhibitor in the advanced/metastatic setting or discontinued from prior therapy due to intolerance. * Participants must have received 1 to 3 lines of systemic treatment in the metastatic setting, which can include anti-PD-1/PD-L1 therapy (if PD-L1 positive), chemotherapy, and anti-angiogenic agents. These treatments may be administered concurrently or sequentially. Prior chemotherapy must be limited to 2 lines or less. * Cohort 1C: * Have documented positive test results for an EGFR-sensitizing mutation (EGFR-sensitizing mutation Exon 21-L858R and 19del). * Participants must have received one or two prior lines of systemic therapy for advanced and/or metastatic disease, which must include treatment with an approved EGFR Tyrosine Kinase Inhibitors (TKI), with at least one being a third-generation EGFR TKI. If there is no third-generation EGFR TKI approved as part of SoC by local health authorities in a certain country, failure/progression on any EGFR TKI is acceptable for eligibility. * Participants receiving an EGFR TKI at the time of signing informed consent may continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1. * Prior chemotherapy and amivantamab are permitted only if administered in combination with an EGFR TKI as part of a single line of therapy and as the initial (first-line) treatment for advanced/metastatic disease. Participants must not have received any other systemic therapies (such as chemotherapy, immunotherapy, or targeted agents) for advanced/metastatic disease, unless those treatments were given in combination with an EGFR TKI. * Have experienced progression during or after treatment or discontinued from prior therapy due to intolerance. * Cohort 1D: * Have histologically or cytologically confirmed diagnosis of unresectable or metastatic acral/uveal/mucosal melanoma not amenable to local therapy. * Participants must have: * Previously been treated with a PD-1 or PD-L1 inhibitor, if clinically indicated and available per local SoC, and/or * For participants with Human Leukocyte Antigen Alleles (HLA-A)\*02:01 serotype-positive disease (only applicable for uveal melanoma), previously been treated with tebentafusp-tebn if clinically indicated and available per local SoC, and * Experienced progression during or after the previous treatment or discontinued from prior therapy due to intolerance. * Cohorts 1E and 1F (DDI): * Have histologically or cytologically confirmed diagnosis of unresectable or metastatic advanced solid tumor not amenable to ablative or curative approach including, but not limited to: * Cholangiocarcinoma, including tumors of the intra- and extrahepatic biliary tract and gallbladder * Hepatocellular carcinoma (HCC). * Renal cell carcinoma * Endometrial carcinoma, excluding those classified as true sarcomas * Pancreatic ductal adenocarcinoma (PDAC) (see below other related inclusion criterion) * Neuroendocrine tumor of pancreatic, gastrointestinal, lung, and thymus that is well differentiated, Grade 1 to 3. * NSCLC (Cohort 1F only) * Have experienced disease progression on at least one and no more than three lines of prior therapy or, for Cohort 1E only, discontinued from prior therapy due to intolerance. * (For participants with PDAC only) Have received one or two lines of systemic therapy for metastatic tumors, and have experienced progression or intolerance to the treatment during or following therapy. * Cohort 2A: Have histologically or cytologically confirmed diagnosis of unresectable or metastatic cutaneous melanoma not amenable to local therapy. * Cohort 2B: Have histologically or cytologically confirmed diagnosis of recurrent unresectable or metastatic breast cancer that is documented as HER2-negative and either HR-negative or HR-positive per American Society of Clinical Oncology/College of American Pathologists guidelines. * Cohort 2D: * Histologically and/or cytologically documented metastatic adenocarcinoma and squamous carcinoma of GC/GEJC. (Note: Esophageal squamous-cell carcinoma is excluded). * (2L subgroup): Had disease progression during or after one prior line of anti-cancer therapy for recurrent/metastatic disease. * (3L subgroup): Has received two or more lines of prior anti-cancer therapy for recurrent/metastatic disease. * (HER2-expression positive subgroup): Has received at least one prior line of systemic therapy for recurrent or metastatic disease, including a HER2-targeted agent in accordance with local SoC. * Cohort 2E: * Histologically and/or cytologically documented recurrent unresectable metastatic colorectal adenocarcinoma. * Must have received at least one line to a maximum of three lines of prior SoC treatment for recurrent/metastatic disease. * Cohort 1G and 2F: * Histologically and/or cytologically documented recurrent unresectable metastatic cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histology. * Must have received platinum-based chemotherapy, with or without an anti-PD-(L)1 agent and bevacizumab for metastatic/recurrent disease, unless the patient is not a candidate in the opinion of the treating physician. Key Exclusion Criteria (applicable to all participants and all parts unless otherwise specified): * Have a history of intolerance to treatment with a topoisomerase I inhibitor or intolerance to an ADC that consists of a topoisomerase I inhibitor, including but not limited to topotecan, irinotecan, and deruxtecan (e.g., severe diarrhea). * Have an uncontrolled concomitant or intercurrent illness that contra-indicates study participation, limits compliance with study procedures or substantially increases the risk of incurring adverse events, including: * Bleeding diathesis or active hemorrhage, * Active infection, * Child-Pugh class B or C cirrhosis, * Known pulmonary disease with significant impact in lung function * Oncologic emergencies or complications (e.g., malignant hypercalcemia, superior vena cava syndrome, carcinoid syndrome that is unstable and with available alternative therapies), * Psychiatric or abuse condition * Infectious colitis Grade ≥2 not resolved to Grade 1 within 72 hours within the past 3 months. * Have LVEF \<50% by either echocardiography or multi-gated acquisition (scanning) within 28 days before randomization/enrollment. * Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization/enrollment. * Have a history of (non-infectious) interstitial lung disease (ILD) /pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. Asymptomatic interstitial changes caused by previous radiation therapy, chemotherapy, or other factors such as smoking are acceptable. * Are a participant of child-bearing potential who are pregnant or breastfeeding or are planning pregnancy within 225 days (\~7.5 months) after receiving last dose of BNT326 and within 6 months after last dose of pumitamig, whichever is longer. * Are potentially fertile males, who are planning to father children during the study or within 135 days (\~4.5 months) after the last dose of BNT326 and within 6 months after last dose of pumitamig, whichever is longer. * Are subject to exclusion periods from another investigational study. * Specific to pumitamig: Participants with significant risks of hemorrhage or evidence of major coagulation disorders as specified in the protocol. * Specific to pumitamig: Have a history of intolerance to treatment with an anti-vascular endothelial growth factor, anti-PD-1/PDL-1, or similar substance, including, but not limited to, bevacizumab, ramucirumab, atezolizumab, pembrolizumab, nivolumab, or other related therapies. * Cohort 1E: Have histological diagnosis of fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC. NOTE: Other protocol defined Inclusion/Exclusion criteria apply.

Study sites (19)

AZ

CA

CT

FL

GA

MA

MI

NC

NY

OH

PA

TX

UT

WI