A Phase 1/2a Dose Escalation and Cohort Expansion Study for Safety, Tolerability, and Efficacy of BMS-986156 Administered Alone and in Combination with Nivolumab (BMS-936558, anti PD-1 Monoclonal Antibody) in Advanced Solid Tumors
- Conditions
- all solid tumors, except primary CNS tumors, in escalation phaseNSCLC, cervical carcinoma, bladder cancer, squamous cell carcinoma head and neck, ovarian cancer and hepatocellular carcinoma in Expansion phaseadvanced solid tumorscancer
- Registration Number
- NL-OMON47516
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 22
For escalation phase (group A and B):
- Signed Written Informed Consent including consent for (archived or fresh) tumor biopsy samples
- at least 18 years old and have histologic or cytologic confirmation of a malignancy that is advanced (metastatic and/or unresectable) with measureable disease
- Subjects must have received, and then progressed or been intolerant to, at least one standard treatment regimen in the advanced or metastatic setting or standard therapy is not possible or refused.
- All solid tumor histologies will be permitted except subjects with primary CNS tumors, or with CNS metastases as the only site of active disease
- ECOG performance status of <= 1
- at least one lesion with measurable disease as defined by RECIST v1.1
- Subjects with prior exposure to therapy with any agent specifically targeting checkpoint
pathway inhibition or any agent specifically targeting T-cell co-stimulation
pathways except anti-GITR antibody permitted after a washout period of 4 weeks
- Prior palliative radiotherapy must have been completed at least 2 weeks prior to first dose
of study drug
- Adequate organ function
- Comply with visit and treatment schedule, sample collection for laboratory tests, and required study follow-up;For expansion phase (group C and D and E):
- Signed Written Informed Consent including consent for (archived and fresh) tumor biopsy samples
- at least 18 years old and have histologic or cytologic confirmation of a malignancy that is advanced (metastatic and/or unresectable) with measureable disease
-The following tumor types will be permitted:
i. Non-Small Cell Lung Cancer (NSCLC): cohort 1 (part C) en cohort 3 (part D) and cohort 10 (part E)
1) All subjects with non-squamous histology must have known EGFR and ALK status
2) Subjects with an activating EGFR mutation must have received an EGFR tyrosine kinase inhibitor
3) Subjects with an ALK translocation must have received an ALK inhibitor
4) Cohort 1 (Part C) and Cohort 3 (Part D): NSCLC subjects with progressive or recurrent disease (per RECIST v1.1) during or after anti-PD-1 or anti-PD-L1 therapy following prior platinum doublet-based chemotherapy
ii. Cervical Cancer: Cohort 2 (Part C) and Cohort 4 (Part D) and cohort 9 (part E)
1) Persistent, recurrent or metastatic cervical cancer with documented disease progression
2) Squamous, adenosquamous or adenocarcinoma histology - confirmation of the original primary tumor is required
3) Must have had at least one prior platinum based regimen
4) Confirmation of tumor HPV status: Prior testing results are acceptable if known. If tumor HPV status is unknown, subjects must consent to allow their submitted archived tumor tissue sample in the form of block or unstained slides to be tested for confirmation of tumor HPV status. Both HPV positive and negative subjects are eligible to enroll
iii. Bladder Cancer: Cohort 5 (part D) and cohort 10 (part E)
1) Histological or cytological evidence of metastatic or surgically unresectable transitional urothelium involving the bladder, urethra, ureter, or renal pelvis
2) Minor histologic variants (< 50% overall) are acceptable
3) Subjects must have metastatic or surgically unresectable disease
4) Subjects must have progression or recurrence after treatment: with at least 1 platinum-containing chemotherapy regimen for metastatic or surgically-unresectable locally
- Known or suspected central nervous system (CNS) metastases, untreated
CNS metastases, or with the CNS as the only site of disease are excluded. However,
subjects with controlled brain metastases will be allowed to enroll.
- Carcinomatous meningitis
- Participation in any prior clinical study with nivolumab > this criteria is deleted in revised protocol nr 3
- Subjects with prior malignancy, except when a second malignancy is diagnosed more than 2 years ago treated with currative intent
- Any anti-cancer therapy within 4 weeks to start of study drug or prior therapy with anti-GITR antibodies
- Active, known or suspected autoimmune disease
- Interstitial lung disease or chronic Obstructive Pulmonary Disease (including pneumonitis)
- A condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications
- Uncontrolled or significant cardiovascular disease (including history of myocarditis)
- History of any chronic hepatitis (does not apply for hepatocellular cancer) or testing positive for HIV
- Active infection <= 7 days prior to initiation of study drug therapy
- Latent or active TBC
- Major surgeries within 4 weeks of study drug administration
- Allergies and adverse drug reaction
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Safety Outcome Measures:<br /><br>Safety assessments will be based on comprehensive medical review of adverse<br /><br>event reports, vital sign measurements, ECGs, physical examinations, and<br /><br>results of laboratory tests. Adverse events will be assessed continuously<br /><br>during the study and for 100 days after the last treatment. The incidence of<br /><br>observed adverse events will be tabulated and reviewed for potential<br /><br>significance and clinical importance.<br /><br><br /><br>Efficacy Measures:<br /><br>Disease assessment with CT and/or MRI, as appropriate, will be performed at<br /><br>baseline and every 8 weeks until disease progression. Once disease progression<br /><br>is noted, no more protocol required tumor assessments are needed unless<br /><br>treatment is continued beyond progression. in this case, tumor assessments will<br /><br>continue every 8 weeks until confirmed disease progression or study treatment<br /><br>is discontinued.</p><br>
- Secondary Outcome Measures
Name Time Method