Title
A Phase 1 Open-Label Study Of PF-07985045 as a Single Agent and In Combination with Other Anti-Cancer Agents in Participants with Advanced Solid Tumors

Description
A PHASE 1 OPEN-LABEL STUDY OF PF-07985045 AS A SINGLE-AGENT AND IN COMBINATION WITH OTHER ANTI-CANCER AGENTS IN PARTICIPANTS WITH ADVANCED SOLID TUMORS

Objective
Part 1 Primary Objective:
-To assess safety and tolerability at increasing dose levels of PF-07985045 in successive cohorts of participants with KRAS mutated tumors in order to estimate the Maximum Tolerated Dose for Monotherapy/Recommended Monotherapy Dose for Expansion.

Part 1 Secondary Objectives:
-To characterize the single and multiple dose PK of PF-07985045 as monotherapy.
-To assess any preliminary anti-tumor activity of PF-07985045 as a monotherapy in participants with advanced solid tumor harboring a KRAS mutation.
-To evaluate the effect of food on the PK of PF-07985045 as monotherapy in a subset of participants.
-To evaluate the intended MOA modulation of KRAS inhibition by PF-07985045 by PD changes in downstream proximal biomarkers in tumor biopsy samples of participants with advanced solid tumor malignancies.

Part 2 Primary Objectives:
-(Escalation only): To assess safety and tolerability at two dose levels of PF-07985045 in each combination cohorts of participants with KRAS mutated tumors in order to estimate each combination cohorts for Maximum Tolerated Dose for Combination Therapy/Recommended Combination Therapy Dose for Expansion.
-To assess the safety and tolerability of PF-07985045 in combination with gemcitabine and Nab-paclitaxel in participants with metastatic PDAC tumors harboring a KRAS mutation (1L).
-To evaluate the safety and tolerability of PF-07985045 in combination with cetuximab in participants with metastatic CRC tumors harboring a KRAS mutation (2L).
-To evaluate the safety and tolerability of PF-07985045 in combination with FOLFOX with bevacizumab in participants with metastatic CRC harboring a KRAS mutation (1L).
-To evaluate the safety and tolerability of PF-07985045 in combination with CPI, with or without platinum-based chemotherapy, in participants with metastatic NSCLC harboring a KRAS mutation (1L).
-To assess preliminary anti-tumor activity of PF-07985045 in combination with gemcitabine and Nab-paclitaxel in participants with metastatic PDAC tumors harboring a KRAS mutation (1L).
-To evaluate preliminary anti-tumor activity of PF-07985045 in combination with cetuximab in metastatic CRC tumors harboring a KRAS mutation (2L).
-To evaluate preliminary anti-tumor activity of PF-07985045 in combination with FOLFOX with bevacizumab in participants with metastatic CRC harboring KRAS mutation (1L).
-To evaluate preliminary anti-tumor activity of PF-07985045 in combination with CPI, with or without platinum-based chemo therapy, in participants with metastatic NSCLC harboring a KRAS mutation (1L).

Part 2 Secondary Objectives:
-To assess additional measures of anti-tumor efficacy of PF-07985045 in combination at the recommended dose for further study for each combination.
-To further evaluate the single and multiple dose PK of PF-07985045 in combination with other anti-tumor agents.
-To evaluate the intended MOA modulation of KRAS inhibition by PF-07985045 by PD changes in downstream proximal biomarkers in tumor biopsy samples of participants with advanced solid tumor malignancies.

Treatment Drug: PF-07985045
Combination Product: Gemcitabine
Combination Product: Nab-paclitaxel
Combination Product: Cetuximab
Combination Product: Fluorouracil
Combination Product: Oxaliplatin
Combination Product: Leucovorin
Combination Product: Bevacizumab
Combination Product: Pembrolizumab
Combination Product: Sasanlimab
Combination Product: pemetrexed
Combination Product: Cisplatin
Combination Product: Paclitaxel
Combination Product: Carboplatin
Combination Product: PF-07284892

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Anal; Bladder; Brain/Central Nervous System; Breast; Cervix; Colon and Rectum; Endocrine cancers; Esophagus; Gastrointestinal cancers, other; Genitourinary cancers, other; Head and Neck; Hematologic cancers, other; Ill-Defined Sites; Kidney; Liver; Lung; Melanoma/Skin cancer; Ovary; Pancreas; Prostate; Sarcoma; Stomach; Thyroid; Uterus

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital