BMS CA022-001: Phase 1/2a First-In-Human Study of BMS-986218 Monoclonal Antibody Alone and in Combination with Nivolumab in Advanced Solid Tumors
Indication :

Tumeurs solides avancées


Sponsor :

BMS


Phase :

I, II


Ligne :

3ème (ou plus)


Traitement :

anticorps monoclonal BMS-986218 seul et en association avec le nivolumab


Spécificités :
  • histologic or cytologic confirmation of a solid tumor that is advanced (metastatic, recurrent and/or unresectable)
  • have at least one soft-tissue lesion accessible for biopsy

Site :

CHUV


Contact(s) :
Martina Imbimbo
Investigateur Principal

CHUV
Département d'Oncologie

Rue du Bugnon 46
Lausanne
1011

+41 79 556 96 12
martina.imbimbo@chuv.ch

Primary objective :

Caractériser la sécurité, la tolérance et la toxicité de l'anticorps monoclonal anti-CTLA4-NF (BMS-986218) en monothérapie ou en association avec le nivolumab chez des patients atteints de tumeurs solides avancées.
Évaluer la sécurité et l'efficacité de l'anticorps monoclonal anti-CTLA4-NF (BMS-986218) en monothérapie en comparaison avec l'ipilimumab chez des patients atteints d'un mélanome avancé déjà traité par immunothérapie anti-PD-1/PD-L1.


Inclusion criteria :
  • Participants must be at least 18 years old and have histologic or cytologic confirmation of a solid tumor that is advanced (metastatic, recurrent and/or unresectable) with measurable disease per RECIST v1.1 or per PCWG 3 criteria for prostate and have at least one soft-tissue lesion accessible for biopsy.
  • Eastern Cooperative Oncology Group Performance Status of 0 or 1.
  • Part 1B: Select solid tumor histologies will be permitted during dose escalation, except for participants with CNS metastases as the only site of active disease. The included histologies will be NSCLC (squamous and adenocarcinoma), gastric adenocarcinoma (including GE junction), TNBC, CRC (adenocarcinoma), pancreatic adenocarcinoma, metastatic castrate resistant prostate adenocarcinoma, transitional cell (urothelial) carcinoma (TCC) of urinary bladder, and SCCHN (oral cavity, pharyngeal, oropharyngeal, hypopharynx, and laryngeal tumors only). Any other cancers of the head and neck, including salivary gland and neuroendocrine tumors, are excluded from enrollment. Histologically confirmed recurrent or metastatic carcinoma of the nasopharynx, SCC or other cancers of the skin of head and neck, and non-squamous histologies are not allowed. Additional tumor histologies may also be included by the Sponsor.
    Participants must have received, and then progressed, relapsed, or been intolerant to at least 2 systemic therapy regimens with proven survival benefit in the advanced or metastatic setting according to tumor type, where available.
  • Part 2A: Participants with advanced stage cutaneous melanoma who have received standard therapies with proven survival benefit including prior immunotherapy with an anti-PD-1 or anti-PD-L1 containing regimen and must have progressive or recurrent disease after prior PD-1/PD-L1 directed therapy. Participants must not have received prior anti-CTLA-4 therapy in the advanced or metastatic setting. Additionally, participants with cutaneous melanoma must have also been offered mutation-directed therapy, if indicated, that has proven survival benefit; if a participant refuses such therapy, it must be documented in the medical record. No more than 1 intervening therapy is allowed but not required between prior anti-PD-1/anti-PD-L1 containing regimen and BMS-986218. No more than 70% of the randomized participants should have had progression of disease within a period of 6 months of start of therapy with anti-PD-1/PD-L1 agent. Only cutaneous melanoma is allowed. All other melanoma (eg, ocular, mucosal) are not allowed.
  • Part 2B: Participants must have received, and then progressed, relapsed, or been intolerant to at least 2 standard systemic therapies with proven survival benefit according to their tumor types in the advanced or metastatic setting, if available. If the participant refuses or is not eligible for these regimens, the reason must be documented in the medical record. Additionally, participants must have progressed or have recurrent disease after prior immunotherapy with anti-PD-1/anti-PD-L1 either by itself or in combination with other systemic therapy agents. No more than 1 intervening therapy is allowed but not required between prior anti-PD-1/anti-PD-L1 containing regimen and BMS-986218. Participants who have been intolerant to prior immunotherapy are excluded. Prior anti-CTLA4 therapy is allowed for no more than 20% of participants, and details of treatment (including dates, doses, and response) must be available.
    (1) Lung/NSCLC (adenocarcinoma and squamous cell carcinoma); additionally for NSCLC, all participants with adenocarcinoma must have known EGFR, ALK, and ROS-1 status. Participants with an activating EGFR mutation, ALK translocation, or ROS-1 mutation must have received appropriate inhibitor therapy.
    (2) Other tumor histologies may also be included by the Sponsor.

Exclusion criteria :
  • Participants with primary CNS malignancies, or tumors with CNS metastases as the only site of disease, will be excluded. Participants with controlled brain metastases; however, will be allowed to enroll.
  • Cytotoxic agents, unless at least 4 weeks have elapsed from last dose of prior anti-cancer therapy and initiation of study therapy.
  • Non-cytotoxic agents, unless at least 4 weeks or 5 half-lives (whichever is shorter) have elapsed from the last dose of prior anti-cancer therapy and the initiation of study therapy. If 5 half-lives is shorter than 4 weeks, agreement with the Sponsor/Medical Monitor (or designee) is mandatory.
  • Prior immunotherapy treatments, unless at least 4 weeks or 5 half-lives (whichever is shorter) have elapsed from the last dose of immune therapy and initiation of study therapy.
  • Prior participation in an anti-CTLA-4-NF clinical study or therapy.
  • Participants who have received prior curative radiation therapy must have been completed at least 4 weeks prior to study drug administration. Prior focal palliative radiotherapy must have been completed at least 2 weeks before study drug administration.
  • Continued luteinizing hormone-releasing hormone (LHRH)/gonadotropin-releasing hormone (GnRH) agonist therapy in men with castration-resistant prostate cancer after progression on an initial androgen deprivation regimen is allowed.