Neoplasm MetastasisPhase 1NCT04135352
A Study of Intratumoral/Intralesional Administration of V938 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic or Recurrent Malignancies (V938-001)
A Phase 1 study testing 200 mg of pembrolizumab and V938 in people with Neoplasm Metastasis, run by Merck Sharp & Dohme LLC at 6 sites in 3 countries.
Trial summary
The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics, and V938 shedding in participants with advanced/metastatic or recurrent malignancies who receive V938 in combination with pembrolizumab (MK-3475). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasm Metastasis
- What is being tested?
- 200 mg of pembrolizumab and V938
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 4 Nov 2019to 24 Aug 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For Dose-escalation arms (Doses A-D): Have a histologically confirmed advanced/metastatic solid tumor and have received, been intolerant to, or been ineligible for treatments known to confer clinical benefit.
- For Dose Expansion Arm A: Have a histologically confirmed Stage III (unresectable) or Stage IV cutaneous melanoma and have received and progressed following 1 or 2 prior lines of systemic treatments for metastatic melanoma which must include 1 line of treatment with PD-1 or PD-L1 immune checkpoint inhibitor either as monotherapy or in combination with other therapy.
- For Dose Expansion Arm B: Have a histologically confirmed advanced head and neck squamous cell carcinoma (HNSCC) and have received and progressed following 1 or 2 prior lines of systemic treatments for metastatic HNSCC which must include 1 line of treatment with PD-1 or PD-L1 immune checkpoint inhibitor either as monotherapy or in combination with other therapy.
- For Dose Expansion Arms A and B: Have at least 1 lesion that is amenable to both intratumoral (IT) injection and biopsy and have at least 1 distant and/or discrete noninjected lesion that is measurable per RECIST 1.1 criteria.
- For Dose-escalation Cohorts 2a, 3a, or 4a and Expansion Cohorts (Arms A and B) ONLY: Have baseline biopsy performed from 1 of the injectable lesions that are planned for IT injection and with tumor tissue provided.
- For all arms: Have at least 1 cutaneous or subcutaneous lesion amenable to IT injection and must be measurable and meet 1 of the following criteria per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1):
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- A cutaneous or subcutaneous lesion ≥1 cm in longest diameter for solid tumors, or ≥1.5 cm in short axis for a nodal lesion in participants with solid tumor. The longest diameter for an injectable lesion must be ≤10 cm for both solid tumors and nodal lesions in participants with solid tumors.
- Multiple coalescing, superficial lesions that in aggregate have a longest diameter of ≥1 cm and ≤10 cm.
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
- Show adequate organ function.
- Male participants are eligible to participate if they agree to the following during the intervention period and for at least 120 days: either be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR must agree to use contraception unless confirmed to be azoospermic. Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- Female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies:
- Is not a woman of childbearing potential (WOCBP)
- Is a WOCBP and using a contraceptive method that is highly effective, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days after the last dose of study intervention.
- HIV-infected participants must have well controlled HIV on antiretroviral therapy (ART), per study criteria.
Who cannot join
- Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study intervention or has not recovered from any adverse events (AEs) that were due to cancer therapeutics administered more than 4 weeks earlier. Participants receiving ongoing replacement hormone therapy for endocrine immune-related AEs will not be excluded from participation in this study.
- Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer, or other in-situ cancers.
- Has clinically active central nervous system metastases and/or carcinomatous meningitis.
- Has had a severe hypersensitivity reaction to treatment with the monoclonal antibody/components of the study intervention or has a history of any contraindication or has a severe hypersensitivity to any components of pembrolizumab (≥Grade 3).
- Has an active infection requiring therapy.
- Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis.
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- Has an active autoimmune disease that has required systemic treatment in the past 2 years except vitiligo or resolved childhood asthma/atopy.
- Is on chronic systemic steroid therapy in excess of replacement doses (prednisone ≤10 mg/day is acceptable), or on any other form of immunosuppressive medication.
- Participants with known Hepatitis B or C infections or known to be positive for hepatitis B antigen/hepatitis B virus DNA or hepatitis C antibody or RNA.
- HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
- Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention.
- Has not fully recovered from any effects of major surgery without significant detectable infection.
- Has received a live-virus vaccine within 30 days of planned treatment start.
- Is currently participating and receiving study intervention in a study of an investigational agent or has participated and received study intervention in a study of an investigational agent or has used an investigational device within 28 days of administration of V938.
- Has a history of re-irradiation for HNSCC at the projected injection site.
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
United States3 sites
MD Anderson Cancer Center ( Site 0001)
Houston, Texas, 77030
Huntsman Cancer Institute ( Site 0004)
Salt Lake City, Utah, 84112
UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0002)
San Francisco, California, 94158
Israel2 sites
Rambam Health Care Campus-Oncology Division ( Site 0020)
Haifa, 3109601
Chaim Sheba Medical Center ( Site 0021)
Ramat Gan, 5265601
Canada1 site
Princess Margaret Cancer Centre ( Site 0010)
Toronto, Ontario, M5G 2M9
About this study
Official title: A Phase 1/1b, Open-label Clinical Study of Intratumoral/Intralesional Administration of V938 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic or Recurrent Malignancies
The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics, and V938 shedding in participants with advanced/metastatic or recurrent malignancies who receive V938 in combination with pembrolizumab (MK-3475). The primary objective is to determine the safety and tolerability and to identify a recommended Phase 2 dose (RP2D) of V938 administered in combination with pembrolizumab.
Read the detailed description
Due to discontinuation of V938-001, all ongoing participants who completed V938 plus pembrolizumab treatment may be enrolled in an extension study (KN587) to continue pembrolizumab monotherapy for a total of 35 cycles since the first dose in V938-001 and to be monitored as appropriate.
- Conditions
- Neoplasm Metastasis
- Being tested
- 200 mg of pembrolizumab, V938
- Keywords
- Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
- Medical subject headings
- Neoplasm Metastasis, Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
200 mg of pembrolizumabDrug
Also called MK-3475
Participants receive 200 mg of pembrolizumab intravenously Q3W for a maximum of 35 21-day cycles.
V938Biological
Participants receive V938 intratumorally in cycles 1-7. Each cycle is 21 days.
| Study group | Role | What they receive |
|---|---|---|
| V938 Dose A + delayed pembrolizumab | Experimental | This arm will enroll participants with advanced/metastatic or recurrent solid tumors. Participants receive Dose A of V938 intratumorally in cycles 1-7. Participants also receive 200 mg of pembrolizumab intravenously once every 3 weeks (Q3W) beginning with cycle 2 for a maximum of 35 cycles. Each cycle is 21 days. Receives: Drug: 200 mg of pembrolizumab; Biological: V938 |
| V938 Dose B + delayed pembrolizumab | Experimental | This arm will enroll participants with advanced/metastatic or recurrent solid tumors. Participants receive Dose B of V938 intratumorally in cycles 1-7. Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 2 for a maximum of 35 cycles. Each cycle is 21 days. Receives: Drug: 200 mg of pembrolizumab; Biological: V938 |
| V938 Dose C + delayed pembrolizumab | Experimental | This arm will enroll participants with advanced/metastatic or recurrent solid tumors. Participants receive Dose C of V938 intratumorally in cycles 1-7. Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 2 for a maximum of 35 cycles. Each cycle is 21 days. Receives: Drug: 200 mg of pembrolizumab; Biological: V938 |
| V938 Dose D + delayed pembrolizumab | Experimental | This arm will enroll participants with advanced/metastatic or recurrent solid tumors. Participants receive Dose D of V938 intratumorally in cycles 1-7. Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 2 for a maximum of 35 cycles. Each cycle is 21 days. Receives: Drug: 200 mg of pembrolizumab; Biological: V938 |
| V938 Dose B + immediate pembrolizumab | Experimental | This arm will enroll participants with advanced/metastatic or recurrent solid tumors. Participants receive Dose B of V938 intratumorally in cycles 1-7. Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 1 for a maximum of 35 cycles. Each cycle is 21 days. Receives: Drug: 200 mg of pembrolizumab; Biological: V938 |
| V938 Dose C + immediate pembrolizumab | Experimental | This arm will enroll participants with advanced/metastatic or recurrent solid tumors. Participants receive Dose C of V938 intratumorally in cycles 1-7. Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 1 for a maximum of 35 cycles. Each cycle is 21 days. Receives: Drug: 200 mg of pembrolizumab; Biological: V938 |
| V938 Dose D + immediate pembrolizumab | Experimental | This arm will enroll participants with advanced/metastatic or recurrent solid tumors. Participants receive Dose D of V938 intratumorally in cycles 1-7. Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 1 for a maximum of 35 cycles. Each cycle is 21 days. Receives: Drug: 200 mg of pembrolizumab; Biological: V938 |
| Dose Expansion Arm A, Melanoma | Experimental | This arm will enroll only participants with with a diagnosis of stage III (unresectable) and Stage IV melanoma (any line of therapy). Participants receive V938 at the recommended Phase 2 Dose, determined by analysis of the Dose A-C arms, intratumorally in cycles 1-7. Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 1 for a maximum of 35 cycles. Each cycle is 21 days. Receives: Drug: 200 mg of pembrolizumab; Biological: V938 |
| Dose Expansion Arm B, HNSCC | Experimental | This arm will only enroll participants with a diagnosis of advanced/metastatic head and neck squamous cell carcinoma (HNSCC). Participants receive V938 at the recommended Phase 2 Dose, determined by analysis of the Dose A-C arms, intratumorally in cycles 1-7. Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 1 for a maximum of 35 cycles. Each cycle is 21 days. Receives: Drug: 200 mg of pembrolizumab; Biological: V938 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)
DLT was defined as a treatment-related adverse event (AE) including the following: Grade (Gr) 4 nonhematologic toxicity (not laboratory), Gr 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia or Gr 4 thrombocytopenia of any duration or Gr 3 thrombocytopenia associated with clinically significant bleeding, Gr 3 non-hematological AE with the exception of fatigue lasting ≤72 hours, Gr 3 nausea, vomiting, diarrhea or rash, any Gr 3 or Gr 4 nonhematologic that lead to hospitalization or abnormality persisting for >1 week or resulting in a drug induced liver injury (DILI), febrile neutropenia Gr 3 or Gr, prolonged delay (>2 weeks) in initiating cycle 3 (for Cohorts 1-4) or cycle 2 (for cohorts 2a-4a) due to study intervention-related toxicity, intervention-related toxicity that caused study discontinuation or missing >1 injection of V938 as a result of drug-related AE(s) during the first 2 cycles (for cohorts 1-4) or during the first cycle (for cohort 2a-4a), Gr 5 toxicity
Measured: Up to ~ 42 days for cohort 1, 2, 3 and 4; Up to ~ 21 days for cohorts 3a and 4a
Number of Participants Who Experienced an Adverse Event (AE)
Number of participants who experienced an AE defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study treatment
Measured: Up to ~ 28 months
Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued treatment due to an AE was assessed.
Measured: Up to ~ 25 months
Secondary outcomes (5)
Objective Response Rate (ORR)
ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions), as assessed by the investigator. In solid tumors, assessment will be based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) and modified RECIST 1.1 for immune-based therapeutics (iRECIST). The percentage of participants who experience a CR or PR based on the above criteria will be presented.
Measured: Up to ~ 33 months
Area Under the Concentration-Time Curve From 0 to 6 Hours Postdose (AUC0-6) for V938 Ribonucleic Acid (RNA) in Plasma
The AUC0-6 for V938 RNA in plasma was calculated.
Measured: Cycle 1 (C1) Day1 (D1), C1D8 and C2D1. Each Cycle is 21 days.
Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) in Plasma
The Cmax for V938 RNA in plasma was reported.
Measured: Cycle 1 (C1) Day1 (D1), C1D8 and C2D1. Each Cycle is 21 days.
Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR)
Shedding raises the possibility of transmission of oncolytic products from treated to untreated individuals. Participants treated with V938 may excrete virus via urine, respiratory tract, or GI tract after the V938 administration. The samples from the participants were collected for evaluation of virus shedding. The presence of V938 viral RNA (pfu/ml) using qRT-PCR assay was assessed in oral cavity/throat, urine, injection site, and anus to detrmine the environmental viral shedding.
Measured: Predose cycle 1 on 3 separate days, and cycles 3, 5, 8, 9, and 10 on day 1. 2 and 4-6 hours postdose cycle 1 day 1. Each cycle is 21 days.
Number of Participants With NDV Infectivity in Excretory Tissue Samples
Participants treated with V938 may excrete virus via urine, respiratory tract, or GI tract after the V938 administration. The positive virus shedding samples that were analyzed in viral shedding were further assessed for NDV infectivity. NDV infectivity was measured by cell-based assay.
Measured: Predose cycle 1 on 3 separate days, and cycles 3, 5, 8, 9, and 10 on day 1. 2 and 4-6 hours postdose cycle 1 day 1. Each cycle is 21 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2019
- Study start4 Nov 2019
- Primary completion24 Aug 2022
- Study completion24 Aug 2022
Why it stopped: Business Reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neoplasm MetastasisStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04135352
- Sponsor's protocol ID
- V938-001
- Other IDs
- V938-001, 2020-003431-25
- Status last verified
- Sep 2024
- First submitted
- 10 Oct 2019
- Last updated
- 12 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/1b, Open-label Clinical Study of Intratumoral/Intralesional Administration of V938 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic or Recurrent Malignancies
- ClinicalTrials.gov ID
- NCT04135352
- Acronym / sponsor ID
- V938-001
- Conditions
- Neoplasm Metastasis
- Keywords
- Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business Reasons
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 4 Nov 2019 (actual)
- Primary completion
- 24 Aug 2022 (actual)
- Study completion
- 24 Aug 2022 (actual)
- First posted
- 22 Oct 2019 (actual)
- Results
- Posted 12 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics, and V938 shedding in participants with advanced/metastatic or recurrent malignancies who receive V938 in combination with pembrolizumab (MK-3475). The primary objective is to determine the safety and tolerability and to identify a recommended Phase 2 dose (RP2D) of V938 administered in combination with pembrolizumab.
Detailed description
Due to discontinuation of V938-001, all ongoing participants who completed V938 plus pembrolizumab treatment may be enrolled in an extension study (KN587) to continue pembrolizumab monotherapy for a total of 35 cycles since the first dose in V938-001 and to be monitored as appropriate.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| V938 Dose A + delayed pembrolizumab | Experimental | Drug: 200 mg of pembrolizumab, Biological: V938This arm will enroll participants with advanced/metastatic or recurrent solid tumors. Participants receive Dose A of V938 intratumorally in cycles 1-7. Participants also receive 200 mg of pembrolizumab intravenously once every 3 weeks (Q3W) beginning with cycle 2 for a maximum of 35 cycles. Each cycle is 21 days. |
| V938 Dose B + delayed pembrolizumab | Experimental | Drug: 200 mg of pembrolizumab, Biological: V938This arm will enroll participants with advanced/metastatic or recurrent solid tumors. Participants receive Dose B of V938 intratumorally in cycles 1-7. Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 2 for a maximum of 35 cycles. Each cycle is 21 days. |
| V938 Dose C + delayed pembrolizumab | Experimental | Drug: 200 mg of pembrolizumab, Biological: V938This arm will enroll participants with advanced/metastatic or recurrent solid tumors. Participants receive Dose C of V938 intratumorally in cycles 1-7. Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 2 for a maximum of 35 cycles. Each cycle is 21 days. |
| V938 Dose D + delayed pembrolizumab | Experimental | Drug: 200 mg of pembrolizumab, Biological: V938This arm will enroll participants with advanced/metastatic or recurrent solid tumors. Participants receive Dose D of V938 intratumorally in cycles 1-7. Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 2 for a maximum of 35 cycles. Each cycle is 21 days. |
| V938 Dose B + immediate pembrolizumab | Experimental | Drug: 200 mg of pembrolizumab, Biological: V938This arm will enroll participants with advanced/metastatic or recurrent solid tumors. Participants receive Dose B of V938 intratumorally in cycles 1-7. Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 1 for a maximum of 35 cycles. Each cycle is 21 days. |
| V938 Dose C + immediate pembrolizumab | Experimental | Drug: 200 mg of pembrolizumab, Biological: V938This arm will enroll participants with advanced/metastatic or recurrent solid tumors. Participants receive Dose C of V938 intratumorally in cycles 1-7. Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 1 for a maximum of 35 cycles. Each cycle is 21 days. |
| V938 Dose D + immediate pembrolizumab | Experimental | Drug: 200 mg of pembrolizumab, Biological: V938This arm will enroll participants with advanced/metastatic or recurrent solid tumors. Participants receive Dose D of V938 intratumorally in cycles 1-7. Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 1 for a maximum of 35 cycles. Each cycle is 21 days. |
| Dose Expansion Arm A, Melanoma | Experimental | Drug: 200 mg of pembrolizumab, Biological: V938This arm will enroll only participants with with a diagnosis of stage III (unresectable) and Stage IV melanoma (any line of therapy). Participants receive V938 at the recommended Phase 2 Dose, determined by analysis of the Dose A-C arms, intratumorally in cycles 1-7. Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 1 for a maximum of 35 cycles. Each cycle is 21 days. |
| Dose Expansion Arm B, HNSCC | Experimental | Drug: 200 mg of pembrolizumab, Biological: V938This arm will only enroll participants with a diagnosis of advanced/metastatic head and neck squamous cell carcinoma (HNSCC). Participants receive V938 at the recommended Phase 2 Dose, determined by analysis of the Dose A-C arms, intratumorally in cycles 1-7. Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 1 for a maximum of 35 cycles. Each cycle is 21 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- For Dose-escalation arms (Doses A-D): Have a histologically confirmed advanced/metastatic solid tumor and have received, been intolerant to, or been ineligible for treatments known to confer clinical benefit.
- For Dose Expansion Arm A: Have a histologically confirmed Stage III (unresectable) or Stage IV cutaneous melanoma and have received and progressed following 1 or 2 prior lines of systemic treatments for metastatic melanoma which must include 1 line of treatment with PD-1 or PD-L1 immune checkpoint inhibitor either as monotherapy or in combination with other therapy.
- For Dose Expansion Arm B: Have a histologically confirmed advanced head and neck squamous cell carcinoma (HNSCC) and have received and progressed following 1 or 2 prior lines of systemic treatments for metastatic HNSCC which must include 1 line of treatment with PD-1 or PD-L1 immune checkpoint inhibitor either as monotherapy or in combination with other therapy.
- For Dose Expansion Arms A and B: Have at least 1 lesion that is amenable to both intratumoral (IT) injection and biopsy and have at least 1 distant and/or discrete noninjected lesion that is measurable per RECIST 1.1 criteria.
- For Dose-escalation Cohorts 2a, 3a, or 4a and Expansion Cohorts (Arms A and B) ONLY: Have baseline biopsy performed from 1 of the injectable lesions that are planned for IT injection and with tumor tissue provided.
Key exclusion criteria (16 listed)
- Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study intervention or has not recovered from any adverse events (AEs) that were due to cancer therapeutics administered more than 4 weeks earlier. Participants receiving ongoing replacement hormone therapy for endocrine immune-related AEs will not be excluded from participation in this study.
- Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer, or other in-situ cancers.
- Has clinically active central nervous system metastases and/or carcinomatous meningitis.
- Has had a severe hypersensitivity reaction to treatment with the monoclonal antibody/components of the study intervention or has a history of any contraindication or has a severe hypersensitivity to any components of pembrolizumab (≥Grade 3).
- Has an active infection requiring therapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 200 mg of pembrolizumabAlso: MK-3475Participants receive 200 mg of pembrolizumab intravenously Q3W for a maximum of 35 21-day cycles. | Drug | Dose Expansion Arm A, Melanoma, Dose Expansion Arm B, HNSCC, V938 Dose A + delayed pembrolizumab, V938 Dose B + delayed pembrolizumab, V938 Dose B + immediate pembrolizumab, V938 Dose C + delayed pembrolizumab, V938 Dose C + immediate pembrolizumab, V938 Dose D + delayed pembrolizumab, V938 Dose D + immediate pembrolizumab |
| V938Participants receive V938 intratumorally in cycles 1-7. Each cycle is 21 days. | Biological | Dose Expansion Arm A, Melanoma, Dose Expansion Arm B, HNSCC, V938 Dose A + delayed pembrolizumab, V938 Dose B + delayed pembrolizumab, V938 Dose B + immediate pembrolizumab, V938 Dose C + delayed pembrolizumab, V938 Dose C + immediate pembrolizumab, V938 Dose D + delayed pembrolizumab, V938 Dose D + immediate pembrolizumab |
Primary outcome
Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)
Time frame: Up to ~ 42 days for cohort 1, 2, 3 and 4; Up to ~ 21 days for cohorts 3a and 4a
DLT was defined as a treatment-related adverse event (AE) including the following: Grade (Gr) 4 nonhematologic toxicity (not laboratory), Gr 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia or Gr 4 thrombocytopenia of any duration or Gr 3 thrombocytopenia associated with clinically significant bleeding, Gr 3 non-hematological AE with the exception of fatigue lasting ≤72 hours, Gr 3 nausea, vomiting, diarrhea or rash, any Gr 3 or Gr 4 nonhematologic that lead to hospitalization or abnormality persisting for >1 week or resulting in a drug induced liver injury (DILI), febrile neutropenia Gr 3 or Gr, prolonged delay (>2 weeks) in initiating cycle 3 (for Cohorts 1-4) or cycle 2 (for cohorts 2a-4a) due to study intervention-related toxicity, intervention-related toxicity that caused study discontinuation or missing >1 injection of V938 as a result of drug-related AE(s) during the first 2 cycles (for cohorts 1-4) or during the first cycle (for cohort 2a-4a), Gr 5 toxicity
Number of Participants Who Experienced an Adverse Event (AE)
Time frame: Up to ~ 28 months
Number of participants who experienced an AE defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study treatment
Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)
Time frame: Up to ~ 25 months
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued treatment due to an AE was assessed.
5 secondary outcomes
Objective Response Rate (ORR)
Time frame: Up to ~ 33 months
Area Under the Concentration-Time Curve From 0 to 6 Hours Postdose (AUC0-6) for V938 Ribonucleic Acid (RNA) in Plasma
Time frame: Cycle 1 (C1) Day1 (D1), C1D8 and C2D1. Each Cycle is 21 days.
Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) in Plasma
Time frame: Cycle 1 (C1) Day1 (D1), C1D8 and C2D1. Each Cycle is 21 days.
Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR)
Time frame: Predose cycle 1 on 3 separate days, and cycles 3, 5, 8, 9, and 10 on day 1. 2 and 4-6 hours postdose cycle 1 day 1. Each cycle is 21 days.
Number of Participants With NDV Infectivity in Excretory Tissue Samples
Time frame: Predose cycle 1 on 3 separate days, and cycles 3, 5, 8, 9, and 10 on day 1. 2 and 4-6 hours postdose cycle 1 day 1. Each cycle is 21 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 200 mg of pembrolizumab and V938 in people with Neoplasm Metastasis, run by Merck Sharp & Dohme LLC at 6 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Israel, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Experienced Dose-Limiting Toxicity (DLT) (time frame: Up to ~ 42 days for cohort 1, 2, 3 and 4; Up to ~ 21 days for cohorts 3a and 4a). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2024.