An open phase I/II study with a complex design for investigational drugs with or without Pembrolizumab or Pembrolizumab alone in participants with melanoma: Substudy MK-3475-02C
Summary description of the study
This study tests several experimental drugs and drug combinations as well as vaccines that are administered before and/or after surgical removal of a melanoma. The immune system plays an important role in tumor control. Pembrolizumab is an antibody that prevents or terminates the immune system's deception by the tumor, thereby enhancing its ability to fight it. MK-7684 is an antibody that increases the activity of specific immune cells, thereby enhancing the body's ability to combat the tumor. The vaccine V937 is based on a virus that has anti-tumor properties. The virus binds to surface structures that are particularly common on tumor cells. This allows the virus to directly attack and destroy tumor cells. The study examines the effect of Pembrolizumab in combination with new substances to determine whether this combination can improve tumor control when the medication is administered before the surgical removal of the melanoma. The goal is to find out which combinations are superior to the currently available drugs and have a good safety profile.
(BASEC)
Intervention under investigation
In this study, approximately 15-25 patients per treatment arm are expected to participate. Each treatment arm consists of a standard treatment with Pembrolizumab and, for all but one arm, an additional treatment with one or more new substances before the surgical removal of the melanoma and Pembrolizumab alone after the operation (standard treatment). New arms may be opened continuously as soon as a new substance from a prior phase I study proves promising.
After careful eligibility assessment, collection of medical history, and detailed information, the participant is included in the study and randomly assigned to one of the three currently open treatment arms. Group 1 receives Pembrolizumab and MK-7684 before the surgical removal of the melanoma and Pembrolizumab after the surgical procedure. Group 2 receives Pembrolizumab and V937 before the surgical removal and Pembrolizumab after the procedure. Group 3 receives Pembrolizumab alone both before and after the surgical removal of the melanoma. Throughout the study, additional treatment arms with other drug combinations may be added as described above.
This study is an open-label study, meaning that both the physician and the participants themselves know which treatment group they have been assigned to.
Participants receive the study medication over a period of approximately one year, with the number of doctor visits varying according to the assigned study arm. After the surgical removal of the melanoma, participants are scheduled for study visits every 3 weeks for a period of 11 months. During this time, health status is regularly monitored for any recurrence or progression of the cancer through imaging studies. The administration of the study medication will depend on the experimental substance and will be given intravenously (MK-7684 and Pembrolizumab) and/or as an injection (V937).
During the study visits, various measures and examinations may take place:
Discussion of health status and current medication, administration of the study medication, imaging procedures (CT and/or MRI scans), digital photographs of the skin, electrocardiogram (ECG), samples of tumor tissue, blood, and urine, as well as examination of vital signs (pulse, blood pressure, etc.).
Follow-Up Phase:
If imaging studies indicate a deterioration of the disease, the next steps will be discussed with the study participant. As part of the study, the participant will be examined at the end (1-2 times in the first month) and then contacted by phone at least every 12 weeks to inquire about their health status.
Participants enter the follow-up phase after completing treatment or after study withdrawal for reasons other than disease progression, where they will be followed up 1-2 times in the first month and then every 3-6 months.
(BASEC)
Disease under investigation
Melanoma is the most severe form of skin cancer and affects adults of all ages. In Switzerland, melanoma is the fifth most common type of cancer. This study examines patients with advanced melanoma that is amenable to surgical removal. Clinical research data indicate that this population has a medical need for new therapeutic options. PD-1 treatments are the new standard after the surgical removal of advanced melanomas and show good results. Nevertheless, melanoma recurs in a significant number of patients at a later stage. The aim of this study is to find new drug combinations to be administered before the surgical removal of the melanoma to reduce the frequency of disease recurrence after surgery and to increase the survival rate. In this study, all patients receive Pembrolizumab.
(BASEC)
• Male or female study participants with histologically/cytologically confirmed diagnosis of melanoma stage IIIB, IIIC, or IIID, which can be surgically removed. • Study participants with 1 or more lymph node metastases that are suitable for tissue sampling and in whom no metastasis spread has occurred within the last 6 months. • Study participants who have not previously received any cancer treatment and/or treatment with oncolytic viruses (viruses that directly or indirectly kill tumor cells) (except for surgery and radiation of the primary tumor) (BASEC)
Exclusion criteria
• Study participants with diagnosed immunodeficiency or study participants receiving chronic steroid therapy or another form of immunosuppressants within 7 days prior to receiving the first dose of the study medication. • Study participants with active autoimmune disease that required systemic treatment within the last 2 years or who have tumors near the airways, major blood vessels, or spinal cord. • Study participants who have previously been treated with a PD-1/PD-L1/L2 antibody or another T-cell receptor-interacting antibody or who have received T-VEC. (BASEC)
Trial sites
Lausanne, Zurich
(BASEC)
Sponsor
Merck Sharp & Dohme LLC, Rahway, New Jersey, USA («MSD»), einer Tochtergesellschaft der Merck & Co., Inc., in der Schweiz vertreten durch MSD Merck Sharp & Dohme AG, Luzern
(BASEC)
Contact
Contact Person Switzerland
Klaudia Georgi
+4158 618 33 88
klaudia.georgi@cluttermsd.comMSD Merck Sharp & Dohme AG
(BASEC)
General Information
Merck Sharp & Dohme LLC
(ICTRP)
Scientific Information
Merck Sharp & Dohme LLC
(ICTRP)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Zurich
(BASEC)
Date of authorisation
02.04.2020
(BASEC)
ICTRP Trial ID
NCT04303169 (ICTRP)
Official title (approved by ethics committee)
MK-3475-02C: A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Design of Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Participants with Melanoma: Substudy 02C (BASEC)
Academic title
A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Design of Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Participants With Melanoma (KEYMAKER-U02): Substudy 02C (ICTRP)
Public title
Substudy 02C: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Stage III Melanoma Who Are Candidates for Neoadjuvant Therapy (MK-3475-02C/KEYMAKER-U02) (ICTRP)
Disease under investigation
Melanoma (ICTRP)
Intervention under investigation
Biological: PembrolizumabBiological: VibostolimabBiological: GebasaxturevBiological: MK-4830Biological: Favezelimab + PembrolizumabDrug: ATRA (ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Inclusion/Exclusion criteria
Inclusion Criteria:
- Has histologically or cytologically confirmed melanoma
- Has clinically detectable and resectable Stage IIIB or IIIC or IIID melanoma
amenable to surgery
- Has been untreated for Stage IIIB, IIIC or IIID melanoma
- surgical resection of primary melanoma is allowed
- prior radiotherapy to the primary melanoma is allowed
- Has provided a baseline tumor biopsy
- Male participants who receive gebasaxturev are abstinent from heterosexual
intercourse or agree to use contraception during the intervention period and for at
least 120 days after the last dose of gebasaxturev
- Male participants who receive ATRA are abstinent from heterosexual intercourse or
agree to use contraception during the intervention period and for at least 7 days
after the last dose of ATRA
- Female participants are not pregnant or breastfeeding and are either not a woman of
child-bearing potential (WOCBP) OR use a contraceptive method that is highly
effective or are abstinent from heterosexual intercourse during the intervention
period and for at least 120 days after the last dose of pembrolizumab, vibostolimab,
gebasaxturev, or MK-4830, favezelimab + pembrolizumab, or 30 days after the last
dose of ATRA, whichever occurs last
- Has adequate organ function
- Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or
less (except alopecia)
Exclusion Criteria:
- Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within
7 days before the first dose of study intervention
- Has a known additional malignancy that is progressing or requires active treatment
within the past 2 years
- Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has ocular or mucosal melanoma
- Has known hypersensitivity including previous clinically significant
hypersensitivity reaction to treatment with another monoclonal antibody (mAb)
- Has an active autoimmune disease that has required systemic treatment in the past 2
years
- Has an active infection requiring systemic therapy
- Has known history of human immunodeficiency virus (HIV)
- Has known history of hepatitis B
- Has a history of (noninfectious) pneumonitis
- Has a history of active tuberculosis (TB)
- Has received prior systemic anticancer therapy within 4 weeks prior to randomization
- Has received prior radiotherapy within 2 weeks of first dose of study intervention
- Has had major surgery <3 weeks prior to first dose of study intervention
- Has received a live or live-attenuated vaccine within 30 days before the first dose
of study intervention
- Has participated in a study of an investigational agent within 4 weeks prior to the
first dose of study intervention
- Has had an allogeneic tissue/solid organ transplant
- Has only mucosal lesions
- Is not nave to Talimogene laherparepvec (TVEC) and other oncolytic viruses (ICTRP)
not available
Primary and secondary end points
Percentage of participants who experience an adverse event (AE);Percentage of participants who discontinue study treatment due to an AE;Pathological complete response (pCR) rate (ICTRP)
Near pathological complete response (near pCR) rate;Pathological partial response (pPR) rate;Recurrence-free survival (RFS) (ICTRP)
Registration date
not available
Incorporation of the first participant
not available
Secondary sponsors
not available
Additional contacts
Medical Director, Merck Sharp & Dohme LLC (ICTRP)
Secondary trial IDs
MK-3475-02C, KEYMAKER-U02, 2023-506314-51-00, U1111-1293-5665, 2019-003978-22, 3475-02C (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT04303169 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available