Solid Tumors

An Open-Label, Multicenter Follow-up Study to Collect Long-term Data on Participants From Multiple Avelumab (MSB0010718C) Clinical Studies

Brief Summary: The main purpose of this study is to monitor the safety and tolerability of avelumab in participants with solid tumors who continue treatment with avelumab under the same treatment regimen as in the parent avelumab study.

Key Eligibility Criteria:

• Participants under enrollment and treatment in an avelumab clinical study under the sponsorship of EMD Serono Research & Development Institute, Inc. / Merck KGaA, Darmstadt, Germany
  • Merck Serono Co., Ltd (Japan)
• Participants currently enrolled in an avelumab parent study and are on active treatment with avelumab or in long-term survival follow-up after treatment
• Participants on active treatment must agree to continue to use highly effective contraception (that is, methods with a failure rate of less than 1% per year) for both male and female participants if the risk of conception exists
• Participants still on active treatment: Known hypersensitivity to any of the study intervention ingredients excluded
• Participant has been enrolled in the comparator arm of avelumab parent study excluded
• Participant has been withdrawn from avelumab parent study for any reason excluded

A phase 3 study of fixed dose combinations of fianlimab and cemiplimab versus relatlimab and nivolumab in participants with unresectable or metastatic melanoma

MOA: Fianlimab (REGN3767) is an anti-LAG-3 monoclonal antibody. Cemiplimab (REGN2810) is an anti-PD-1 antibody.

Key Eligibility Criteria:

• Histologically confirmed unresectable stage III and stage IV (metastatic) melanoma
  • Uveal, acral or mucosal melanoma are not eligible
• No prior systemic therapy for unresectable or metastatic melanoma
  • Pt with adjuvant/neoadjuvant therapy without PD during treatment are eligible if disease-free and treatment-free for over 6 months
  • No prior immune checkpoint inhibitor therapy other than anti-PD-1/ PD-L1
• Measurable disease per RECIST version 1.1
  • Previously irradiated lesions can be used as target lesions only if demonstrated to progress and no other target lesion is available
  • Cutaneous lesions are considered non-target lesions
• Patients must have known BRAFV600 status or submitted sample for assessment

A Multicenter, Open-label, Phase 3 Study to Evaluate the Long-term Safety and Efficacy in Participants who are Currently on Treatment or in Follow-up in Studies That Include Pembrolizumab (MK3475-587)

Brief Summary: The purpose of this study is to evaluate the long-term safety and efficacy of pembrolizumab (MK-3475) in participants from previous Merck pembrolizumab-based parent studies who transition into this extension study.

Key Eligibility Criteria:

• Treated on the parent pembrolizumab studies established by the Sponsor as MK-3475-587 ready.
• Currently receiving pembrolizumab, pembrolizumab based combinations or lenvatinib from parent studies or in a follow-up phase
• Has not received any anticancer systemic treatment since the last dose of pembrolizumab or a pembrolizumab-based combination in First Course Phase.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients excluded
• Has a known additional malignancy that is progressing or requires active treatment excluded

A Phase II, multicentre, multicohort, open-label trial to evaluate the efficacy and safety of oral zongertinib (BI 1810631) for the treatment of selected HER2-mutated or overexpressed/amplified solid tumours 

MOA: Zongertinib is an EGFR wild-type sparing, selective HER2 inhibitor with potent inhibitory activity on all oncogenic HER2 mutations.

Key Eligibility Criteria:

• Subjects with a previously treated, locally advanced unresectable or metastatic solid tumor & a documented HER2 status of:
  • Cohorts 1-6, 11, & 12: HER2 overexpression/amplification
  • Cohorts 7-10 & 13: Known activating HER2 mutations (without overexpression/amplification)
• Subjects must have documented progression after at least one prior therapy (excluding adjuvant/neoadjuvant), and deemed unlikely to benefit from further SOC treatment
• Patients with HER2 overexpressing/amplified mBC or HER2 mutant NSCLC(except where there is co-existing presence of HER2 overexpression/amplification) are excluded
• Patients previously treated with HER2 TKIs are excluded

A Randomized, Double-blind, Placebo-controlled Phase 3 Study to evaluate Dostarlimab as Sequential Therapy after Chemoradiation in Patients with Locally Advanced Unresected Head and Neck Squamous Cell Carcinoma

MOA: Dostarlimab is a humanized anti-PD-1 IgG4 mAb.

Key Eligibility Criteria:

• Unresected LA histologically confirmed HNSCC of the oral cavity,
  oropharynx (OPSCC), hypopharynx or larynx
• OPSCC p16 positive: T4 (N0-N3), M0; N3 (T1-T4), M0
• OPSCC p16 negative: Any T3-T4 (N0-N3), M0; Any N2a-N3 (T1-T4), M0
• Larynx/hypopharynx/oral cavity (independent of p16): Any T3-T4 (N0-
  N3), M0; Any N2a-N3 (T1-T4), M0
• Complete CRT and no metastasis
• Prior systemic, radiation, surgery, immunotherapy or targeted
  therapy, that are not considered part of CRT, are excluded
• Has provided acceptable core or excisional biopsy
• PD-L1 positive tumor CPS ≥ 1 (central testing)
• OPSCC only: p16 IHC positive ≥ 70% (local CINtec assay)

A Phase III, Randomized, Open-Label, Multi-Center, Global Study of Volrustomig as Sequential Therapy Versus Observation in Participants with Unresected Locally Advanced-Head and Neck Squamous Cell Carcinoma (LA-HNSCC) Who Have Not Progressed Following Definitive Concurrent Chemoradiotherapy  (eVOLVE-HNSCC)

MOA: Checkpoint inhibitor Volrustomig (MEDI5752): Monovalent, bispecific, anti-PD-1 / anti-CTLA-4 humanized IgG1 mAb

Key Eligibility Criteria:

• Locally advanced squamous cell carcinoma of the OP, HP, OC, or LX with no evidence of metastatic disease
• Confirmed unresected Stage III-IVA/B
• SOC cCRT with curative intent completed within 12 weeks prior to randomization
• Have not progressed following cCRT with curative intent
• PD-L1 confirmation by central lab prior to randomization
• Tissue acquired <3mo. prior to cCRT or fresh tumor biopsy
• PD-L1 CPS<1 capped at 20% of randomized participants
• OPC only: confirmation of HPV status by local CINtec
  Histology p16 Assay or by central lab

A Phase I/IIa, Open-label, Multi-center Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the ATR Kinase Inhibitor ART0380 Administered Orally as Monotherapy and in Combination to Patients with Advanced or Metastatic Solid Tumors

MOA: ART0380 selectively targets and inhibits ATR activity and blocks the downstream phosphorylation of the serine/threonine protein kinase CHK1.

Key Eligibility Criteria:

• Patients with BRCA mutations or HRD-positive cancer should
  receive an approved PARPi treatment if available
• At least 1 lesion that can be radiologically evaluated by RECIST v1.1
• Patients who are known to be homozygous for the UGT1A1 *6 or *28
  or simultaneously heterozygous for the UGT1A1 *6 and *28 are
  excluded
• Sufficient non-irradiated tumor tissue sample available for analysis
• Cohort B1: Advanced or metastatic solid tumor with complete loss
  of ATM protein (IHC H score 0)
• Cohort B5: Metastatic CRC with complete loss of ATM protein (IHC
  H score 0)
• Patients should have previously received and failed treatment
  with fluoropyrimidine-, oxaliplatin-based chemotherapy

Phase 1/2 Study of Rina-S in Patients with Locally Advanced and/or Metastatic Solid Tumors GCT1184-01 (PRO1184-001)

MOA: Rinatabart sesutecan (Rina-S) is an FRα-directed antibody drug conjugate with an exatecan payload.

Key Eligibility Criteria:

• Cohort B3 – EGFR-mutated NSCLC
  • Must have received EGFR-targeted therapy and plt-based chemo
• Part C – High-grade serous PROC
  • 1-3 prior lines of therapy (1-4 if MIRV was last line)
  • Must have received prior bevacizumab
  • Must have received PARPi if BRCA mutant and PR/CR on plt-based chemo
• Part D – High-grade serous, endometrioid, clear cell OC/PP/FPC
  Cohort D1 – PSOC
  • 1-3 prior lines of therapy
    Cohort D2 – PSOC, PROC, Plt-refractory
  • Plt-refractory must have received ≤2 prior lines of therapy
  • Prior therapy may include bev, PARPi, and MIRV
  • 1-3 prior lines of therapy for PROC
  • 1-4 prior lines of therapy for PSOC

A Clinical Trial of Pembrolizumab (MK-3475) Evaluating Predictive Biomarkers in Subjects with Advanced Solid Tumors (KEYNOTE-158)

Brief Summary: In this study, participants with multiple types of advanced (unresectable and/or metastatic) solid tumors who have progressed on standard of care therapy will be treated with pembrolizumab (MK-3475)

Key Eligibility Criteria:

• Histologically or cytologically-documented, advanced solid tumor
• Radiologically-measurable disease
• Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
• Progression of tumor or intolerance to therapies known to provide clinical benefit
• Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study treatment excluded