臨床研究等提出・公開システム

組織学的又は細胞学的に確定診断された進行性固形がん患者を対象に、MK-1308をMK-3475と併用投与するfirst-in-human、多施設共同、多群、非盲検、非無作為化、第Ⅰ相試験

This is a first-in-human, multicenter, multi-arm, open label, non-randomized, Phase 1 study of MK-1308 in combination with pembrolizumab in participants with a histologically or cytologically confirmed diagnosis of an advanced solid tumor.

1. 用量漸増期：組織学的又は細胞学的に進行性／転移性固形がん（コホート2ではNSCLC を除く）であることが病理報告書で確認された患者。クリニカルベネフィットが得られるあらゆる治療を受けている、これらに不耐容である、不適格である、若しくは拒否しているかは問わない。
2. 用量確認期、A 群、B 群及びC 群：組織学的又は細胞学的にIIIB/IV 期のNSCLC であると新たに診断され、上皮増殖因子受容体（EGFR）変異陰性及び、未分化リンパ腫キナーゼ（ALK）転座陰性である患者。進行性NSCLC に対する全身性の前治療歴がないこと。また、早期病変に対する全身性の前治療歴については、治験薬投与の6ヵ月以上前の術前化学療法及び術後化学療法は許容される。病理報告書に診断名が記載され、治験担当医師が病理判定すること。
3. 用量確認期、D 群： 組織学的又は細胞学的に進行性／転移性SCLC であることが確認された患者。プラチナ製剤の前治療を1レジメン以上受けていること。プラチナ製剤に難治性、抵抗性又は感受性のいずれの場合も組入れ可能である。初回診断時に限局型又は進展型のいずれであっても、現時点で進行性（IIIB/IV 期）である場合組入れ可能である。病理報告書に診断名が記載され、治験担当医師が病理判定すること。
4. 治験実施医療機関の治験担当医師／放射線科医の評価によりRECIST 1.1に基づく測定可能病変を有する患者。
5. Eastern Cooperative Oncology Group (ECOG) Performance Scale のperformance status が0又は1の患者。
6.妊娠可能な女性患者は、治験薬の初回投与前72時間以内に実施した尿検査又は血清妊娠検査結果が陰性でなければならない。また、治験薬最終投与後120日までの治験期間中、適切な避妊法を用いることに同意しなければならない。
7. 妊娠可能な女性パートナーがいる男性患者は、治験薬最終投与後120日までの治験期間中、適切な避妊法を用いることに同意しなければならない。また、この期間中は精子提供をしてはならない。
8. ベースライン時に評価可能な解析用腫瘍検体（新たに採取した腫瘍検体又は保存腫瘍検体のいずれか）の提出が可能な患者。

For Dose Escalation Phase:
- Have any histologically- or cytologically-confirmed advanced/metastatic solid tumor (except NSCLC for Cohorts 2 and 3) by pathology report and have received, been intolerant to, been ineligible for, or refused all treatment known to confer clinical benefit
For Dose Confirmation Phase NSCLC Arms (A, B, C, and E):
- Have newly diagnosed histologically or cytologically-confirmed stage IIIB/stage IV NSCLC. Epidermal growth factor receptor (EGFR)-and anaplastic lymphoma kinase (ALK) translocation-directed therapy is not indicated as primary therapy. Participant must not have received prior systemic treatment for advanced NSCLC or must have received previous neoadjuvant and adjuvant chemotherapies >=6 months before dosing of study drug if prior systemic treatment was given for early stage disease
For Dose Confirmation Phase SCLC Arm (Arm D):
- Have histologically- or cytologically-confirmed metastatic (Stage III/IV) SCLC with progressive disease after >=1 platinum-based chemotherapy regimen. Participants with platinum-sensitive disease are eligible
Have measurable disease by RECIST 1.1 as assessed by the local site investigator/radiology
- Have Eastern Cooperative Oncology Group (ECOG) Performance Scale status of 0 or 1
- A 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 child bearing potential (WOCBP) OR
- Is a WOCBP and using a contraceptive method that is highly effective during the intervention period and for at least 120 days after the last dose of pembrolizumab or pembrolizumab/quavonlimab, whichever comes last
- Female participants of childbearing potential must have negative urine or serum pregnancy test within 24 hours for urine and within 72 hours for serum prior to receiving the first dose of study treatment
- Male participants with a female partner(s) of child-bearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication and refrain from donating sperm during this period
- Must submit an evaluable baseline tumor sample for analysis (either a recent or archival tumor sample)

1. 全試験期共通：CTLA-4を標的とする薬剤による治療歴を有する患者。
2. 用量確認期のみ：PD-1又はPD-L1を標的とする薬剤による治療歴を有する患者。
3. 治験薬の初回投与前4週間（緩和的放射線療法の場合は2週間）以内に化学療法、根治的放射線療法、がんに対する生物学的療法の治療歴を有する患者又は4週間以上前に実施したがん治療による有害事象がCTCAE Grade 1以下まで回復していない患者
4. 現在他の臨床試験に参加している、治験薬の投与を受けている患者又はMK-1308の投与前28日以内に他の臨床試験に参加し、治験薬の投与若しくは医療機器を使用していた患者。

5. 他の悪性腫瘍の既往を有する患者。ただし、根治的治療により3年間悪性腫瘍所見を認めていない患者は除く。
6. 活動性の中枢神経系（CNS）への転移及び／又は癌性髄膜炎を有する患者。
7. 免疫療法による治療歴があり、Grade 3以上の免疫関連有害事象により治療を中止した患者。8. モノクローナル抗体／成分に重度過敏症反応の既往を有する患者。
9. 治療を要とする活動性の感染症を有する患者。
10. 間質性肺疾患の既往を有する患者。
11. 間質性肺疾患／肺臓炎を合併、若しくはステロイド投与が必要な（非感染性の）間質性肺疾患／肺臓炎の既往を有する患者。
12. 炎症性腸疾患の既往を有する患者。
13. 過去2年以内に全身治療を要した活動性の自己免疫疾患に罹患した患者。
14. 重度の心血管疾患を有する患者。
15. 治験薬の初回投与前28日以内に生ワクチンを投与した患者。
16. ヒト免疫不全ウイルス（HIV）、B 型肝炎若しくはC 型肝炎の感染を有する患者。HBs 抗原／HBV DNA 陽性、又はHCV 抗体若しくはHCV-RNA 陽性が確認された患者。
18. 治験の実施を妨げる可能性がある精神疾患又は物質乱用障害を有する患者。
19. 妊娠中、授乳中の患者、又は治験期間中に本人又はパートナーの妊娠を希望する患者。
20. 大手術を受け、重大な感染は検出されていないが、十分に回復していない患者。

- For all phases of the study: Has received previous treatment with another agent targeting cytotoxic T lymphocyte leukocyte antigen (CTLA)-4
For Dose Confirmation Phase:
- Has received previous treatment with another agent targeting programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
- Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study therapy, or has not recovered to Common Toxicity Criteria for Adverse Events (CTCAE) Grade 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier
- Has received lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose of study treatment
- Is currently participating and receiving study therapy in a study of an investigational agent or has participated and received study therapy in a study of an investigational agent or has used an investigational device within 28 days of administration of quavonlimab.
Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years
For Dose Escalation Cohorts (1-3) and Dose Confirmation Arms (A-E):
- Has known untreated central nervous system (CNS) metastases. Has known carcinomatous meningitis
- Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse events (irAE)
- Has had a severe hypersensitivity reaction to treatment with any monoclonal antibody or components of the study drug
- Has any active infection requiring therapy
- Has a history of interstitial lung disease, history of noninfectious pneumonitis that required steroids (or has current pneumonitis), or history of inflammatory bowel disease
- Has an active autoimmune disease that has required systemic treatment in the past 2 years
- Has clinically significant cardiac disease
- Has received a live or live attenuated vaccine within 28 days of planned treatment start
- Has known history of human immunodeficiency virus (HIV) and/or known active Hepatitis B or C infections, and/or known to be positive for hepatitis B surface antigen (HBsAg)/ hepatitis B virus (HBV) DNA
- Has known psychiatric or substance abuse disorders that would interfere with the participant's ability to cooperate with the requirements of the trial
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with screening and for up to 120 days following cessation of pembrolizumab or pembrolizumab/quavonlimab
- Has not fully recovered from any effects of major surgery without significant detectable infection

18歳以上

18age old over

上限なし

No limit

男性・女性

Both

試験完了

completed