A Phase I/II Study of BMS-986340 as Monotherapy and in Combination With Nivolumab or Docetaxel in Participants With Advanced Solid Tumors
Study Identifier:
CA052-002
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
N/A
Recruiting
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Study Summary
To assess the safety, tolerability, and recommended dose(s) of BMS-986340 as monotherapy and in combination with nivolumab or docetaxel in participants with advanced solid tumors.
To evaluate the safety and tolerability, PK, immunogenicity and efficacy of BMS-986340 monotherapy and in combination with nivolumab or docetaxel in patients with advanced solid tumors.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I/II
Sex
Female & Male
Age
18+ years
Study Drug
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting
Requirements information
Inclusion criteria
- Fresh pre-treatment and on-treatment tumor biopsy must be provided for biomarker analysis Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and at least 1 lesion accessible for biopsy. Fine needle biopsy, cytology, and bone lesion biopsies are not acceptable. Eastern Cooperative Oncology Group Performance Status of 0 or 1 Radiographically documented progressive disease on or after the most recent therapy Received standard-of-care therapies, (except for Part 1C, where participants with prior docetaxel use for the advanced/metastatic setting will be excluded), including an available programmed death (ligand)-1 inhibitor known to be effective in the tumor type for which they are being evaluated Advanced or metastatic disease and have received, be refractory to, not be a candidate for, or be intolerant of existing therapies known to provide clinical benefit for the condition of the participant Parts 1A, 1B, and 2A: Advanced or metastatic non-small cell lung cancer, squamous cell carcinoma of head and neck, microsatellite stable colorectal cancer, gastric/ gastroesophageal junction adenocarcinoma, or cervical cancer, and have received, be refractory to, not be a candidate for, or be intolerant of existing therapies known to provide clinical benefit for the condition of the participant Eligible tumor types for each Part are listed below: - Parts 1A and 1B: NSCLC, SCCHN, MSS-CRC, gastric/GEJ adenocarcinoma, cervical cancer (SCC or adenocarcinoma), RCC, UC, PDAC, melanoma, OC, or TNBC. - Parts 2A and 2B: NSCLC, SCCHN, gastric/GEJ adenocarcinoma, or up to 3 additional tumor types from Parts 1A and 1B may be considered based on emerging data. - Part 1C: NSCLC, SCCHN, gastric/GEJ adenocarcinoma, OC, or TNBC. • Other protocol-defined inclusion criteria apply.
- 1Participants must have measurable lesions as evaluated according to the Evaluation Criteria for Treatment of Solid Tumors (RECIST) v1.1 (Appendix 5), and at least one lesion must be available for biopsy. Fine-needle aspiration biopsy, cytology, and bone lesion biopsy are not acceptable.2Participants must have an Eastern American Oncology Cooperative Group Performance Status score of 0 or 1.3Study participants were required to have received standard therapy (except in Part 1C, which excluded participants who had previously used docetaxel for advanced/metastatic disease), including available PD-(L)1 inhibitors known to be effective against the tumor type being evaluated.4NSCLC participants: i) Histologically confirmed NSCLC meeting the staging criteria for stage IIIB, IV, or relapsed disease. ii) Participants must have experienced disease relapse or progression during or after platinum-based doublet chemotherapy for advanced or metastatic disease, or within 6 months of completing platinum-based chemotherapy for localized disease. iii) Participants must have received anti-PD-(L)1 therapy and experienced disease progression during or after that therapy (if available). iv) The status of operational mutations (e.g., epidermal growth factor [EGFR], anaplastic lymphoma kinase [ALK], ROS oncogene 1 [ROS1], transfection rearrangement genes [RET], etc.) must be known (when tested according to national standard treatment practice); participants with operational mutations must have received standard tyrosine kinase inhibitor therapy and experienced disease progression, be intolerant to, or be unsuitable for standard tyrosine kinase inhibitor therapy (as tested according to national standard treatment practice).5For participants with gastric/GEJ adenocarcinoma: i) Participants must have received at least one standard treatment regimen in an advanced or metastatic background, followed by disease progression, recurrence, or intolerance (or disease progression within 6 months of adjuvant therapy). ii) Participants with known human epidermal growth factor receptor 2 (HER2)-positive gastric cancer must have previously received HER2 inhibitor therapy (e.g., trastuzumab). iii) MSI status or mismatch repair status should be documented, if available. iv) Dosage extensions Parts 2A and 2B: Participants must have received anti-PD-(L)1 therapy and experienced disease progression during or after that therapy.6SCCHN participants: i) Participants must have histologically confirmed recurrent or metastatic SCCHN (oral, pharyngeal, larynx) and be ineligible for curative local treatment. Exclusion of any other head and neck cancers, including nasopharyngeal carcinoma, salivary gland, and neuroendocrine tumors, is required. ii) Participants must have experienced disease progression during or after a platinum-based treatment regimen, or be intolerant to platinum-based treatment. iii) Prior radical radiotherapy must have been completed at least 4 weeks prior to the first administration of the study drug. Prior focal palliative radiotherapy must have been completed at least 2 weeks prior to administration of the study drug. iv) Historical human papillomavirus (HPV) status for oropharyngeal carcinoma must be documented. HPV status should be determined using p16 immunohistochemistry (IHC) or HPV polymerase chain reaction (PCR). v) Participants must have received anti-PD-(L)1 therapy and experienced disease progression during or after that therapy (if available).7MSS-CRC participants: i) Participants must have received standard systemic therapy for at least one metastatic and/or unresectable disease, followed by disease progression during or after treatment, intolerance to the therapy, or therapy refractory (or disease progression within 6 months of adjuvant therapy). (1) Prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan monotherapy or multiple dosing regimens is required. (2) Prior anti-angiogenic therapy (e.g., bevacizumab) is required. ii) Participants must have a known MSI status or mismatch repair status. (1) If both MSI molecular testing and MMR IHC testing results are available, both MSS status and normal MMR function are required for enrollment in the study. Patients with high or low microsatellite instability or MMR deficiency are ineligible. iii) KRAS, NRAS, and BRAF status (if known) should be recorded. (1) If RAS is wild-type, prior anti-EGFR therapy (e.g., cetuximab or panitumumab) is required.8Cervical cancer (SCC or adenocarcinoma) participants: i) must have received platinum-based chemotherapy with or without bevacizumab in an advanced or metastatic background and experienced disease progression, recurrence, or intolerance after treatment. ii) MSI status or mismatch repair status should be documented, if available.9Renal cell carcinoma (RCC) participants: i) Participants must have histologically confirmed recurrent or metastatic RCC and be ineligible for curative local treatment. ii) Participants must have experienced disease progression or refractory disease during or after at least two lines of therapy, including prior anti-PD-(L)1 therapy.10Urothelial carcinoma (UC) participants: i) Participants must have histologically confirmed recurrent or metastatic UC and be ineligible for curative local treatment. ii) Participants must have received at least one platinum-based chemotherapy regimen and experienced disease progression, recurrence, intolerance to the treatment, or ineligibility for treatment after treatment, or received platinum-based therapy within 12 months of the perioperative period (neoadjuvant or adjuvant) for cystectomy to treat locally muscle-invasive UC. iii) Participants must be resistant or refractory to anti-PD(L)1-based immunotherapy.11Pancreatic ductal adenocarcinoma (PDAC) participants: i) Participants must have histologically confirmed recurrent or metastatic PDAC and be unsuitable for curative local treatment. ii) Participants must have received at least one prior standard chemotherapy regimen and experienced disease progression or be intolerant to (or unsuitable for) that treatment.12Melanoma participants: i) Participants must have primary melanoma of the skin, extremities, mucous membranes, or unknown origin. Participants with uveal/ocular melanoma are ineligible. ii) Participants must have histologically confirmed recurrent or metastatic melanoma and be ineligible for curative local treatment. iii) Participants must have received at least one standard treatment regimen in an advanced or metastatic background and experienced disease progression, relapse, or intolerance after treatment, including prior anti-PD-(L)1 therapy (if available). iv) Participants must have a known BRAF status. If indicated, participants must have received targeted mutation therapy with proven survival benefit.13Ovarian cancer (OC) participants: i) Participants must have histologically or cytologically confirmed recurrent or metastatic epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer, and be ineligible for curative local treatment. ii) Participants must have received platinum-based chemotherapy and experienced disease progression, recurrence, or intolerance after treatment, or must have experienced disease recurrence or progression within 6 months of completing platinum-based chemotherapy. iii) BRCA1/2-mutant participants must have received PARP inhibitor therapy (if available).14Triple-negative breast cancer (TNBC) participants: i) Participants must have histologically confirmed recurrent or metastatic TNBC and be ineligible for curative local treatment. ii) Disease progression or refractory disease must have occurred during or after at least one chemotherapy regimen for locally advanced or metastatic disease. iii) Participants carrying BRCA1/2 mutations must have received platinum-based regimens (if eligible) and PARP inhibitors (if available). iv) If PD-L1 positive (defined as a combined positive score ≥10), prior immune checkpoint inhibitor therapy is required.
Exclusion criteria
- Women who are pregnant or breastfeeding Primary central nervous system (CNS) malignancy Untreated CNS metastases Leptomeningeal metastases Concurrent malignancy requiring treatment or history of prior malignancy active within 2 years prior to the first dose of study treatment Active, known, or suspected autoimmune disease Condition requiring systemic treatment with either corticosteroids within 14 days or other immunosuppressive medications within 30 days of the first dose of study treatment Prior organ or tissue allograft Uncontrolled or significant cardiovascular disease Major surgery within 4 weeks of study drug administration History of or with active interstitial lung disease or pulmonary fibrosis
- 1Primary malignant tumors of the central nervous system (CNS)22. Untreated CNS metastases. Participants are eligible to participate in the study if their CNS metastases have been treated and their neurological symptoms have returned to baseline (excluding residual signs or symptoms related to CNS treatment). Furthermore, participants must have discontinued corticosteroids or received a stable or reduced dose (≤10 mg/day prednisone [or equivalent]) for at least 2 weeks prior to the first dose of study treatment. Imaging studies performed within 28 days prior to the first dose of study treatment must document the radiographic stability of the CNS lesions and must be performed after completion of any CNS-targeted therapy.3pia mater metastasis4Participants must have a history of concurrent malignancy requiring treatment (present during the screening period) or an active malignancy within 2 years prior to the first dose of study treatment (i.e., participants with a history of malignancy are eligible to participate if they completed treatment at least 2 years prior to the first dose of study treatment and have no evidence of disease). Participants with a history of early basal/squamous cell skin cancer or non-invasive or carcinoma in situ and who received definitive treatment at any time are also eligible to participate in the study.5Participants with active, known, or suspected autoimmune diseases are eligible for enrollment. Participants with type 1 diabetes, hypothyroidism requiring only hormone replacement therapy, skin diseases not requiring systemic treatment (such as vitiligo, psoriasis, or alopecia), or diseases not expected to relapse in the absence of external triggers are also eligible.6Participants had a condition requiring systemic treatment with corticosteroids (>10 mg/day prednisone equivalent) within 14 days prior to the first dose of study treatment or with other immunosuppressive drugs within 30 days prior. In the absence of active autoimmune disease, inhaled or topical steroids, as well as adrenal replacement steroids at doses >10 mg/day prednisone equivalent, were permitted.7Previous organ or tissue allogeneic transplant8Toxicity (excluding hair loss) associated with prior cancer treatment and/or surgery, unless the toxicity resolves, returns to baseline levels or is grade 1, or is considered irreversible.9Participants must not have undergone any major surgery within 4 weeks prior to administration of the study drug. Participants must have recovered from the effects of major surgery or severe traumatic injury for at least 14 days prior to the first administration of the study treatment.10Uncontrolled or major cardiovascular disease, including but not limited to any of the following: i) Myocardial infarction or stroke/transient ischemic attack within the past 6 months. ii) Uncontrolled angina within the past 3 months. iii) Any history of clinically significant arrhythmia (e.g., ventricular tachycardia, ventricular fibrillation, or torsades de pointes). iv) Other clinically significant cardiac history (e.g., cardiomyopathy, congestive heart failure of New York Heart Association class III or IV, pericarditis, or significant pericardial effusion). v) Requirement for daily oxygen therapy related to cardiovascular disease. vi) QT interval (QTcF) prolongation >480 ms, adjusted for heart rate using the Fridericia formula, excluding right bundle branch block. vii) History of myocarditis, regardless of etiology.11A history of active interstitial lung disease or pulmonary fibrosis, or accompanied by active interstitial lung disease or pulmonary fibrosis.12Evidence of active infection requiring systemic antimicrobial, antiviral, or antifungal treatment within ≤7 days prior to the first dose of study treatment (excluding viral infections presumed to be related to the underlying tumor type required for inclusion in the study).13Known HIV positivity, having experienced an opportunistic infection as defined by acquired immunodeficiency syndrome (AIDS) within the past year, or a current CD4 count <350 cells/μL. HIV participants are eligible to participate in the study if they meet the following criteria: i) They have received antiretroviral therapy for at least 4 weeks prior to the first dose of study treatment, as indicated by clinical indication, during the study enrollment period. ii) They continue to receive antiretroviral therapy as indicated by clinical indication during the study enrollment period. iii) Their CD4 count and viral load are monitored by a local healthcare provider according to standard treatment. Note: HIV testing must be performed at a locally mandated research center. If locally mandated, HIV-positive participants must be excluded.14Participants with serious or uncontrolled medical conditions15Received packed red blood cells or platelets transfusion within 2 weeks prior to the first dose of the study treatment.16Any significant acute or chronic medical condition that may interfere with research, treatment, or follow-up17Any known or potential medical or psychiatric illness and/or social cause that the investigator or sponsor believes may cause harm to a participant or may adversely affect a participant's ability to comply with or tolerate the study treatment.18Any illness, including active or uncontrolled infection, or the presence of abnormal laboratory test results, would expose a participant to unacceptable risks if they were to participate in the study.19Previous SARS-CoV-2 infection (if known), including mild or asymptomatic infection within 10 days prior to Day 1 of Period 1, or severe/critical illness within 20 days. i) Acute symptoms must have resolved, and based on investigator assessment and consultation with medical monitors, there must be no sequelae that would place participants at higher risk when receiving study treatment.
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (CIOCC)
Madrid, Spain, 28050
Investigator
Emiliano Calvo
Status
Recruiting
Condition(s) Treated at Site
Cervical cancer
Gastric
Bowel (Colorectal)
Non-Small Cell Lung Cancer
HNSCC
Solid Tumor
Renal
Urinary tract
Pancreas
Melanoma
Ovarian
Breast Cancers
Location
START Madrid, Spain (FJD)
Madrid, Spain, 28040
Investigator
Victor Moreno Garcia
Status
Recruiting
Condition(s) Treated at Site
Cervical cancer
Gastric
Bowel (Colorectal)
Non-Small Cell Lung Cancer
HNSCC
Solid Tumor
Renal
Urinary tract
Pancreas
Melanoma
Ovarian
Breast Cancers