PF-07104091 monotherapy dose escalation

PF-07104091 will be administered orally in combination with palbociclib and fulvestrant

PF-07104091 + palbociclib + fulvestrant

PF-07104091 will be administered orally in combination with palbociclib and letrozole

PF-07104091 + palbociclib + letrozole

PF-07104091 monotherapy dose expansion (SCLC)

PF-07104091 monotherapy dose expansion (ovarian)

PF-07104091 + fulvestrant (post CDK4/6) dose expansion

PF-07104091 + fulvestrant (post 4/6) dose expansion

PF-0704091 + Fulvestrant (post CDK4/6)

CDK2+ fulvestrant (post CDK 4/6) dose escalation

PF-07104091 will be administered orally in combination with fulvestrant

PF-07104091 + Fulvestrant (post CDK4/6)

The cohort of individuals with metastatic NSCLC will be treated with the reICB regimen (anti-PD(L)-1 antibodies+ cyclophosphamide+ bevacizumab) until disease progression or unacceptable toxicity.

* ICI (one of the following): Atezolizumab 1200 mg every 3 weeks/Nivolumab 240 mg every 2 weeks/Pembrolizumab 200 mg every 3 weeks
* Cyclophosphamide 50 mg PO daily
* Bevacizumab 7.5 mg/kg every 3 weeks

reICB regimen (NSCLC)

The cohort of individuals with metastatic cutaneous melanoma will be treated with the reICB regimen (anti-PD(L)-1 antibodies+ cyclophosphamide+ bevacizumab) until disease progression or unacceptable toxicity.

* ICI (one of the following): Nivolumab 240 mg every 2 weeks/Pembrolizumab 200 mg every 3 weeks
* Cyclophosphamide 50 mg PO daily
* Bevacizumab 7.5 mg/kg every 3 weeks

reICB regimen (melanoma)

Aram A. Musaelyan, PhD

폐암 환자를 대상으로 새로운 방사선과 면역치료가 수술 가능성을 높이는지 확인하는 2단계 시험입니다.

Sintilimab is an anti-PD-1 monoclonal antibody. In this study, it is administered intravenously at a fixed dose of 200 mg on Day 1 of each 3-week cycle. Patients receive 2 cycles of sintilimab in combination with platinum-based doublet chemotherapy. The first dose of sintilimab is initiated within 7 days after completion of stereotactic body radiotherapy (SBRT).

Sintilimab

Paclitaxel is a taxane chemotherapeutic agent. In this study, it is specifically used for patients with squamous cell non-small cell lung cancer (NSCLC). It is administered intravenously at a dose of 175 mg/m² on Day 1 of each 3-week cycle. Patients receive 2 cycles of paclitaxel in combination with sintilimab (anti-PD-1 antibody) and carboplatin (platinum-based agent) as part of the neoadjuvant regimen. Standard premedication to prevent hypersensitivity reactions is required prior to each infusion. This systemic chemotherapy phase is initiated within 7 days after the completion of stereotactic body radiotherapy (SBRT) to the primary lung tumor.

Paclitaxel

Carboplatin is a platinum-based chemotherapeutic agent. In this study, it serves as the backbone chemotherapy for all patients, regardless of histology. It is administered intravenously on Day 1 of each 3-week cycle. The dose is calculated using the Calvert formula to achieve a target area under the concentration-time curve (AUC) of 5 mg/mL/min. Patients receive 2 cycles of carboplatin in combination with sintilimab (anti-PD-1 antibody) and either pemetrexed (for non-squamous NSCLC) or paclitaxel (for squamous NSCLC). This chemoinmunotherapy phase commences within 7 days after the completion of stereotactic body radiotherapy (SBRT) to the primary lung tumor.

Carboplatin (AUC 5)

Pemetrexed is an antifolate chemotherapeutic agent. In this study, it is specifically used for patients with non-squamous non-small cell lung cancer (NSCLC). It is administered intravenously at a dose of 500 mg/m² on Day 1 of each 3-week cycle. Patients receive 2 cycles of pemetrexed in combination with sintilimab (anti-PD-1 antibody) and carboplatin (platinum-based agent) as part of the neoadjuvant regimen. To reduce toxicity risks, standard premedication (including folic acid, vitamin B12 supplementation, and corticosteroids) is required as per the product label. This systemic chemotherapy phase is initiated within 7 days after the completion of stereotactic body radiotherapy (SBRT) to the primary lung tumor.

Pemetrexed 500 mg/m2

Stereotactic Body Radiotherapy (SBRT) is a precise, high-dose form of external beam radiation therapy. In this study, SBRT is directed only at the primary lung tumor (not the lymph nodes). The treatment is delivered in 3 fractions (sessions) over approximately 3 days, with a total dose of 24 Gy (8 Gy per fraction). Treatment planning is based on 4D-CT simulation to account for respiratory motion. The SBRT is completed before the initiation of systemic therapy (sintilimab + chemotherapy).

Stereotactic body radiotherapy (SBRT)

Radical lung resection is the planned definitive treatment for eligible patients. Approximately 4 weeks after neoadjuvant therapy, patients first undergo cervical mediastinoscopy for contralateral lymph node assessment. Only those with negative pathology proceed to surgery 2 weeks later. The surgery involves initial video-assisted thoracoscopic dissection of remaining contralateral nodes (specific stations based on primary tumor side) with intraoperative frozen section. If negative, patients undergo immediate repositioning and radical lung resection (lobectomy/pneumonectomy) with ipsilateral lymphadenectomy(right side dissection of lymph nodes in groups 3A, 9R and 10R, left side dissection of lymph nodes in groups 5, 6, 9L and 10L).

non-small cell lung cancer

신틸리맙

파클리탁셀

카보플라틴(AUC 5)

페메트렉세드 500mg/m2

정위체 방사선 치료(SBRT)

비소세포폐암

Hong Prof. Yang, M.D., PH.D.

N3 양성 비소세포폐암에 대한 신보조 SBRT 후 신틸리맙과 화학요법 병용 치료

Cohort 1: Olvi-Vec administered over 3 consecutive days at 0.5,0.5,0.5 x 10e9 pfu followed 2 to 3 weeks later with platinum-doublet chemotherapy + Physician's Choice of ICI.

Cohort 2: Olvi-Vec administered over 3 consecutive days at 1,1,1 x 10e9 pfu followed 2 to 3 weeks later with platinum-doublet chemotherapy + Physician's Choice of ICI.

Cohort 3: Olvi-Vec administered over 4 consecutive days at 1,2,3 x 10e9 pfu followed 2 to 3 weeks later with platinum-doublet chemotherapy + Physician's Choice of ICI.

Olvi-Vec is an engineered oncolytic vaccinia virus

Olvimulogene nanivacirepvec

Administered according to local practice.

Platinum chemotherapy: carboplatin or cisplatin

Non-platinum chemotherapy: paclitaxel or nab-paclitaxel for squamous cell NSCLC or pemetrexed for nonsquamous cell NSCLC

Physician's Choice of Immune Checkpoint Inhibitor: pembrolizumab, nivolumab, cemiplimab, atezolizumab, durvalumab

Olvi-Vec will be administered at the dose and schedule selected from the single-arm run-in Olvi-Vec dose escalation cohorts followed 2 to 3 weeks later with platinum-doublet chemotherapy + Physician's Choice of ICI.

Docetaxel starts in Week 0 and continues until disease progression is assessed by the BICR.

Docetaxel

Patients randomized into the Active Comparator can cross-over to receive the same treatment as given in the Experimental Arm following determination of (1) disease progression by BICR after receiving docetaxel treatment and (2) confirming eligibility.

Hamdy Mohtaseb, MD

Kiran Penta

Gopal Kunta, MD

Sumit Sawhney, MD

Kylee Charlemagne

Edgardo Santos, MD

Jenrrys Mejias

Jonathan Matias

Luis Rangel, MD

Richa Dawar, MD

Handy Del Sol Bello

Marianna Wefer

Javier Perez Fernandez, MD

Santosh Nair, MD

Anamaria Astudillo

Harshad Amin, MD

Heather Austin

Faisel Musa, MD

Catherine Maples

Jeffrey Margolis, MD

Research

Erev Tubb, MD

Carrie Smith

Kim Roby

Nashat Gabrail, MD

Marian Heaven, BSN

James Uyeki, MD

Isabel Navarrete

Dustyn Tobin, MD

Amir Rasheed, MD

non randomized, open-label extension cohort, evaluating the safety of acetazolamide in combination with platinum and etoposide-based radiochemotherapy in patients with Localized small lung cancer

Radiation therapy will be combined with platinum and etoposide-based chemotherapy combined with 3-6 tablets per day of acetazolamide during the entire course of therapy (dosage appropriate to the inclusion phase).

acetazolamide in combination with platinum and etoposide-based radiochemotherapy

non randomized, open-label extension cohort, evaluating the safety of acetazolamide in combination with radioimmunotherapy in patients with extensive small cell lung cancer

acetazolamide in combination with radioimmunotherapy in patients with extensive SCLC

Jérôme Doyen, MD

The study will evaluate efficacy \& toxicity of SBRT in stage III NSCLC

SBRT to primary tumor and lymph nodes in stage III NSCLC when gross disease is \< 6 cms

+ 팔보시클립 + 레트로졸, PF-07104091 단독 요법 용량 확장(난소암), PF-07104091 단독 요법 용량 확장(소세포폐암), PF-07104091 + 풀베스트란트(CDK4/6 억제 후), PF-0704091 + 풀베스트란트(CDK4/6 억제 후)

reICB 요법(비소세포폐암), reICB 요법(흑색종)

N3 양성 비소세포폐암에 대한 신보조 SBRT 후 신틸리맙과 화학요법 병용 치료

광범위 소세포폐암 환자에서 아세타졸아미드와 백금 및 에토포사이드 기반 방사선화학요법 병용, 아세타졸아미드와 방사면역요법 병용

3기 비소세포폐암에서 SBRT